Prognostic contributions of the underlying inflammatory disease and acute organ dysfunction in critically ill patients with systemic rheumatic diseases.

BACKGROUND: Knowledge about the clinical features, outcomes and predictors of short-term mortality in critically ill patients with systemic rheumatic disease (SRD) requires further characterization. METHODS: Single center retrospective observational cohort study of 149 critically ill patients with SRD followed in a French medical intensive care unit over a 20-year period. Multivariate logistic regression was used to identify predictors of day-30 mortality. RESULTS: Most patients (63%) had systemic lupus erythematosus, rheumatoid arthritis, or systemic sclerosis. The critical illness usually developed late after the diagnosis of SRD (median time to ICU admission 82 months, IQR [9-175] in the 127 patients with a previous diagnosis of SRD). Two-thirds of patients were taking immunosuppressive drugs to treat their SRD. Reasons for ICU admission were infection (47%), SRD exacerbation (48%), and iatrogenic complications (11%); the most common organ failure was acute renal failure. Thirty-day mortality was 16%. Predictors of 30-day mortality were the LODS score on day 1 (OR 1.3 (1.06-1.48)), bacterial pneumonia (OR 3.8 (1.03-14.25)), need for vasoactive drugs (OR 7.1 (1.83-27.68)), SRD exacerbation (OR 4.3 (1.15-16.53)), and dermatomyositis (OR 9.2 (1.05-80.78)) as the underlying disease. Year of ICU admission was not significantly associated with 30-day survival. CONCLUSION: Patients with SRD are mostly admitted in the ICU with infection or SRD exacerbation, and can be treated with immunosuppressive therapy and life-sustaining interventions with acceptable 30-day mortality. Death is associated with both the severity of the acute medical condition and the characteristics of the underlying SRD.

Severe post-renal acute kidney injury, post-obstructive diuresis and renal recovery.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? The pathophysiology of post-renal acute kidney injury (PR-AKI), i.e. caused by urinary tract obstruction, has been extensively studied in animal models but clinical studies on this subject are outdated, and/or have focused on the mechanisms of 'post-obstructive diuresis' (POD), a potentially life-threatening polyuria that can develop after the release of obstruction. In severe PR-AKI, the risk of occurrence of POD is high. POD occurrence predicts renal recovery without the persistence of severe chronic kidney failure. In the present study, the occurrence of POD and the persistence of chronic renal sequelae could be predicted early from clinical variables at admission before the release of obstruction. OBJECTIVE: • To identify predictors of post-obstructive diuresis (POD) occurrence or severe chronic renal failure (CRF) persistence after the release of urinary tract obstruction in the setting of post-renal acute kidney injury (PR-AKI). PATIENTS AND METHODS: • Bi-centre retrospective observational study of all patients with PR-AKI treated in two intensive care units (ICUs) from 1998 to 2010. • Clinical, biological and imaging characteristics on admission and after the release of obstruction were analysed with univariate and, if possible, multivariate analysis to search for predictors of (i) occurrence of POD (diuresis >4 L/day) after the release of obstruction; (ii) persistence of severe CRF (estimated glomerular filtration rate <30 mL/min/1.73 m(2), including end-stage CRF) at 3 months. RESULTS: • On admission, median (range) serum creatinine was 866 (247-3119) µmol/L. • POD occurred in 34 (63%) of the 54 analysable patients. On admission, higher serum creatinine (Odds ratio [OR] 1.002 per 1 µmol/L, 95% confidence interval [CI] 1.000-1.004, P = 0.004), higher serum bicarbonate (OR 1.36 per 1 mmol/L, 95% CI 1.13-1.65, P < 0.001), and urinary retention (OR 6.96, 95% CI 1.34-36.23, P = 0.01) independently predicted POD occurrence. • Severe CRF persisted in seven (21%) of the 34 analysable patients, including two (6%) cases of end-stage CRF. Predictors of severe CRF persistence after univariate analysis were: lower blood haemoglobin (P < 0.001) and lower serum bicarbonate (P = 0.03) on admission, longer time from admission to the release of obstruction (P = 0.01) and absence of POD (P = 0.04) after the release of obstruction. CONCLUSIONS: • In severe PR-AKI treated in ICU, POD occurrence was a frequent event that predicted renal recovery without severe CRF. • POD occurrence or severe CRF persistence could be predicted early from clinical and biological variables at admission before the release of obstruction.

Should dialysis be offered to cancer patients with acute kidney injury?

OBJECTIVES: Cancer patients are at high risk for acute kidney injury (AKI), which is associated with high mortality when renal replacement therapy is required. Because physicians might be reluctant to offer dialysis to patients with malignancies, we sought to appraise outcomes in critically ill cancer patients (mainly with hematological malignancies) who received renal replacement therapy for AKI complicating cancer management. DESIGN: Cohort study including consecutive patients who received renal replacement therapy for AKI complicating cancer management, over a 42-month period. Their mortality was compared with that of non-cancer patients who received renal replacement therapy in the same center over the same study period (control group). SETTING: A 12-bed medical intensive care unit in a university hospital. RESULTS: 94 critically-ill cancer patients met the inclusion criteria. Median SAPS II was 53 (IQR 40-75) and median Logistic Organ Dysfunction score was 7 (IQR 5-10). The etiology of AKI was multiple in most patients (248 identified factors in 93 patients). Hospital mortality was 51.1%. Two variables were independently associated with hospital mortality: the severity of associated organ failures at ICU admission (OR, 1.33; 95% CI, 1.11-1.59; per point) and renal function deterioration after ICU admission (OR, 5.42; 95% CI, 1.62-18.11). Characteristics of the malignancy were not associated with hospital mortality. The presence of cancer had no detectable influence on hospital mortality after adjustment for gender, age, acute severity as assessed by the SAPS II score, and chronic health status [OR 1.2, 95% CI 0.63-2.27; p=0.57]. CONCLUSION: ICU admission should be considered in selected critically ill cancer patients with AKI requiring renal replacement therapy.

Ability of family members to predict patient's consent to critical care research.

OBJECTIVE: A European Union Directive provides for the designation of a surrogate who can consent to or refuse inclusion of an incapacitated patient in research studies. The accuracy with which surrogates consent to research on behalf of patients has not been evaluated in the intensive care unit (ICU). METHODS: A prospective multicenter study was conducted in ten ICUs of the French Famirea study group between July and October 2004. Two hypothetical studies were simultaneously submitted to the patient, surrogate, and physician at the time that the patient was discharged to a ward. One study involved minimal risk and the other greater-than-minimal risk to the patients. RESULTS: With the minimal risk study there was patient-surrogate discrepancy in 32% of cases and patient-physician discrepancy in 25%. Corresponding figures with the greater-than-minimal risk study were 42% and 46%. None of the collected variables differed significantly between cases with and without patient-surrogate discrepancy. CONCLUSIONS: Family members designated to serve as surrogate decision makers may fail to accurately consent to research for critically ill patients in one-third to nearly one-half of cases.

End-of-life family conferences: rooted in the evidence.

Critical care clinicians no longer consider family members as visitors in the intensive care unit. Family-centered care has emerged from the results of qualitative and quantitative studies evaluating the specific needs of families of patients dying in the intensive care unit. In addition, interventional studies have established that intensive and proactive communication empowers family members of dying patients, helping them to share in discussions and decisions, if they so wish. In addition to intensive communication, interventional studies have highlighted the role of nurses, social workers, and palliative care teams in reducing family burden, avoiding futile life-sustaining therapies, and providing effective comfort care. End-of-life family conferences are formal, structured meetings between intensivists and family members. Guidelines for organizing these conferences take into account the specific needs of families, including reassurance that the patient's symptoms will be adequately managed; honest clear information about the patient's condition and treatment; a willingness on the part of physicians to listen and respond to family members and to address their emotions; attention to patient preferences; clear explanations about surrogate decision making; and continuous, compassionate, and technically proficient attention to the patient's needs until death occurs. Means of improving end-of-life care have been identified in epidemiologic and interventional studies. End-of-life family conferences constitute the keystone around which excellent end-of-life care can be built.

Heparin binding EGF is necessary for vasospastic response to endothelin.

Endothelin-1 (ET-1), a powerful vasoconstrictor, is involved in vasospastic diseases such as coronary artery disease and subarachnoidal hemorrhage, as well as in renal and cardiovascular fibrotic remodeling. Transactivation of the epidermal growth factor receptor (EGFR) mediates ET-1 signaling in vascular smooth muscle cells (VSMCs) and isolated arteries. Moreover, EGFR is required for a full constrictive response to ET-1. However, the relevant mechanisms mediating EGFR transactivation in response to ET-1 have not been identified. The present study used isolated arteries and VSMCs to investigate the role of the EGFR ligand heparin binding-epidermal growth factor (HB-EGF) in ET-1-induced transactivation of EGFR, intracellular calcium mobilization, and VSMCs contraction. While baseline blood pressures were similar in HB-EGF-deficient and in wild-type littermate mice, the vasoconstrictor actions of ET-1 were attenuated in HB-EGF-/- animals. In isolated mouse carotid artery segments mounted in an arteriograph, ET-1 caused only a weak increase in isovolumetric tone in HB-EGF-deficient vessels, and this effect was mimicked by inhibition of EGFR tyrosine kinase or phosphoinositide 3-kinase (PI3K) in wild-type arteries with or without endothelium, indicating a specific role in VSMCs. EGFR or PI3K inhibitors had no effect on KCl-induced contraction, which was normal in HB-EGF-deficient mice. To confirm that the abnormal responses in HB-EGF-deficient mice were due to impaired EGFR signaling, we studied VSMCs from waved-2 (wa2) mice; these animals have a mutation causing a partial loss of function of EGFR tyrosine kinase activity. The ET-1-induced calcium peak was reduced by 30% in VSMCs from wa2 mice and from HB-EGF-/- mice. This effect was reproduced by preincubation of wild-type VSMCs with EGFR inhibitor AG1478 and PI3K inhibitors LY294002 and wortmannin. ProHB-EGF is bound to the cell membrane and released after cleavage by metalloproteinases; its action may contribute to effects of GPCR agonists on cell growth. Pretreatment of mouse VSMCs with batimastat, a metalloproteinase inhibitor, significantly attenuated ET-1-induced [Ca(2+)](i) response in wild-type cells. Human proHB-EGF has been shown to be the endogenous receptor for Corynebacterium diphteriae toxin (DT). Mutated DT toxin (CRM197) is devoid of toxicity but it neutralizes HB-EGF binding to EGFR. Pretreatment of human VSMCs from internal mammary arteries with CRM197 significantly blunted ET-1-stimulated calcium transients. In conclusion, these findings suggest that the mechanism of ET-1-induced vasoconstriction involves HB-EGF-mediated transactivation of the EGFR. This functional cascade requires modulation of agonist-induced calcium transient by EGFR and PI3K with extremely fast kinetics, suggesting a novel paradigm for GPCR-mediated calcium signaling, which may offer future therapeutic targets.

Time course of organ dysfunction in thrombotic microangiopathy patients receiving either plasma perfusion or plasma exchange.

INTRODUCTION: Few studies have investigated adults with thrombotic microangiopathy (TMA) requiring intensive care unit (ICU) admission, and the treatment remains controversial. OBJECTIVE: To describe causes, outcomes, prognostic factors, and daily organ-failure score changes in adults with TMA requiring ICU admission. DESIGN: A 3-yr single-center cohort study. PATIENTS: The patients were 36 adults with TMA admitted to a teaching-hospital medical ICU between January 2000 and June 2003. RESULTS: Of the 36 patients, 22 received plasma infusion and 15 underwent plasma exchange. All patients had anemia and thrombocytopenia at ICU admission, and 13 had neurologic impairment. Median creatinine clearance was 55.2 mL/min (interquartile range, 28.8-75.4). No patient had congenital TMA. Causative factors included microbiologically documented infection in 14 patients, allogeneic transplantation in 7 patients, and concomitant or subsequent systemic disease in 7 patients; 6 patients were human immunodeficiency virus-positive, 5 had drug-induced TMA, 2 were pregnant, and 2 had cancer. In 10 patients, no causative factors were identified. Plasma exchange was associated with a statistically significant decrease in hospital mortality (0 vs. 7 deaths; p < .001). Moreover, daily organ-failure scores were significantly lower in the plasma-exchange group from day 3 to day 9. Patients in the plasma-exchange group received a larger volume of plasma. CONCLUSION: Plasma exchange may be associated with faster resolution of organ failure and with improved survival for patients with TMA requiring ICU admission.

Clinical review: specific aspects of acute renal failure in cancer patients.

Acute renal failure (ARF) in cancer patients is a dreadful complication that causes substantial morbidity and mortality. Moreover, ARF may preclude optimal cancer treatment by requiring a decrease in chemotherapy dosage or by contraindicating potentially curative treatment. The pathways leading to ARF in cancer patients are common to the development of ARF in other conditions. However, ARF may also develop due to etiologies arising from cancer treatment, such as nephrotoxic chemotherapy agents or the disease itself, including post-renal obstruction, compression or infiltration, and metabolic or immunological mechanisms. This article reviews specific renal disease in cancer patients, providing a comprehensive overview of the causes of ARF in this setting, such as treatment toxicity, acute renal failure in the setting of myeloma or bone marrow transplantation.

Care at the end of life in critically ill patients: the European perspective.

PURPOSE OF REVIEW: Care surrounding end-of-life has become a major topic in the intensive care medicine literature. Cultural and regional variations are associated with transatlantic debates about decisions to forego life-sustaining therapies and lead to recent international statements. The aim of this review is to provide insight into the decisions to forego life sustaining therapies and end-of-life care in Europe. RECENT FINDINGS: Although decisions to forego life-sustaining therapies are increasingly made in European countries, frequency and characteristics of end-of-life care are still heterogeneous. Moreover, even though many determinants of these variations have been identified, epidemiologic and interventional studies still provide additional information. In agreement with public opinions, recent European laws have emphasized the patient's autonomy. In real life, advance care planning is rarely used. Decisions are often made by caregivers (physicians and nurses) or families, these latter being less involved than in North America. Not only ethic divergences between physicians but also cultural variations account for this disparity. SUMMARY: To optimize end-of-life care in the intensive care unit, there is an urgent need for the development of palliative and multidisciplinary care in Europe. Furthermore, it highlights the need for culturally competent care, adapted to needs and values of every single patient and family. In addition, a lack of communication with families and within the medical team, an uninformed public about end-of-life issues, and insufficient training of intensive care unit staff are crucial barriers to end-of-life care development. Special awareness of professionals and innovative research are needed to promote a high-standard of end-of-life care in the intensive care unit.

Intensive care in patients with newly diagnosed malignancies and a need for cancer chemotherapy.

OBJECTIVE: Patients with newly diagnosed cancer responsible for organ failures may require intensive care unit (ICU) admission and immediate chemotherapy. Outcomes in this population have not been studied. DESIGN: Prospective observational cohort study. SETTING: Teaching hospital. SUBJECTS: All patients admitted to the ICU, from January 1997 to June 2003, for organ failures due to newly diagnosed, untreated cancer and deemed necessary to receive immediate cancer chemotherapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the period of 6.5 yrs, 100 patients met the study criteria: 43 had acute leukemia, 37 lymphoma, and 12 solid tumors. Median Simplified Acute Physiology Score II was 39 (30-48) points, and median Logistic Organ Dysfunction score was 5 (3-7) points. Three variables were independently associated with 30-day mortality: need for vasopressor therapy (odds ratio, 6.01; 95% confidence interval, 1.86-19.4), mechanical ventilation (odds ratio, 6.36; 95% confidence interval, 1.76-22.94); and hepatic failure (odds ratio, 7.76; 95% confidence interval, 1.25-48.27). Overall survival was 60% after 30 days and 49% after 180 days. CONCLUSIONS: Mortality was chiefly dependent on the nature and number of organ failures, not on the nature or stage of the malignancy. The 30-day and 180-day survival rates indicate that, in this selected group of patients, advanced disease at cancer diagnosis should not lead to refusal of ICU admission. Moreover, administration of chemotherapy in the intensive care unit is feasible, and although the mortality rate is high, routine ICU admission of patients with newly diagnosed cancer, specific organ failure, and the need for administration of chemotherapy in the ICU deserves evaluation.

Outcome of cancer patients considered for intensive care unit admission: a hospital-wide prospective study.

PURPOSE: To evaluate the outcome of cancer patients considered for admission to the intensive care unit (ICU). PATIENTS AND METHODS: Prospective, one-year hospital-wide study of all cancer and hematology patients, including bone marrow transplantation patients, for whom admission to the ICU was requested. RESULTS: Of the 206 patients considered for ICU admission, 105 patients (51%) were admitted. Of the 101 patients who were not admitted, 54 patients (26.2%) were considered too sick to benefit, and 47 patients (22.8%) were considered to be too well to benefit from the ICU. Of these 47 patients, 13 patients were admitted later. Survival rates after 30 and 180 days were significantly associated with admission status (P < .0001). Remission of the malignancy (odds ratio [OR], 3.37; 95% CI, 1.25 to 9.07) was independently associated with ICU admission, whereas poor chronic health status (OR, 0.38; 95% CI, 0.16 to 0.74) and solid tumor (OR, 0.43; 95% CI, 0.24 to 0.78) were associated with ICU refusal. In admitted patients, 30-day and 6-month survival rates were 54.3% and 32.4%, respectively. Of the patients considered too sick to benefit from ICU admission, 26% were alive on day 30 and 16.7% on day 180. Among patients considered too well to benefit, the 30-day survival rate was a worrisome 78.7%. Calibration of the Mortality Probability Model (the only score available at triage) was of limited value for predicting 30-day survival (area under the curve, 0.62). CONCLUSION: Both the excess mortality in too-well patients later admitted to the ICU and the relatively good survival in too-sick patients suggest the need for a broader admission policy.

The prognosis of acute respiratory failure in critically ill cancer patients.

Acute respiratory failure (ARF) in patients with cancer is frequently a fatal event. To identify factors associated with survival of cancer patients admitted to an intensive care unit (ICU) for ARF, we conducted a prospective 5-year observational study in a medical ICU in a teaching hospital in Paris, France. The patients were 203 cancer patients with ARF mainly due to infectious pneumonia (58%), but also noninfectious pneumonia (9%), congestive heart failure (12%), and no identifiable cause (21%). We measured clinical characteristics and ICU and hospital mortality rates.ICU mortality was 44.8% and hospital mortality was 47.8%. Noninvasive mechanical ventilation was used in 79 (39%) patients and conventional mechanical ventilation in 114 (56%), the mortality rates being 48.1% and 75.4%, respectively. Among the 14 patients with late noninvasive mechanical ventilation failure (>48 hours), only 1 survived. The mortality rate was 100% in the 19 noncardiac patients in whom conventional mechanical ventilation was started after 72 hours. By multivariable analysis, factors associated with increased mortality were documented invasive aspergillosis (odds ratio [OR], 2.13; 95% confidence intervals [CI], 1.05-14.74), no definite diagnosis (OR, 3.85; 95% CI, 1.26-11.70), vasopressors (OR, 3.19; 95% CI, 1.28-7.95), first-line conventional mechanical ventilation (OR, 8.75; 95% CI, 2.35-35.24), conventional mechanical ventilation after noninvasive mechanical ventilation failure (OR, 17.46; 95% CI, 5.04-60.52), and late noninvasive mechanical ventilation failure (OR, 10.64; 95% CI, 1.05-107.83). Hospital mortality was lower in patients with cardiac pulmonary edema (OR, 0.16; 95% CI, 0.03-0.72). Survival gains achieved in critically ill cancer patients in recent years extend to patients requiring ventilatory assistance. The impact of conventional mechanical ventilation on survival depends on the time from ICU admission to conventional mechanical ventilation and on the patient's response to noninvasive mechanical ventilation.