Trends in clinical profiles, organ support use and outcomes of patients with cancer requiring unplanned ICU admission: a multicenter cohort study.

PURPOSE: To describe trends in outcomes of cancer patients with unplanned admissions to intensive-care units (ICU) according to cancer type, organ support use, and performance status (PS) over an 8-year period. METHODS: We retrospectively analyzed prospectively collected data from all cancer patients admitted to 92 medical-surgical ICUs from July/2011 to June/2019. We assessed trends in mortality through a Bayesian hierarchical model adjusted for relevant clinical confounders and whether there was a reduction in ICU length-of-stay (LOS) over time using a competing risk model. RESULTS: 32,096 patients (8.7% of all ICU admissions; solid tumors, 90%; hematological malignancies, 10%) were studied. Bed/days use by cancer patients increased up to more than 30% during the period. Overall adjusted mortality decreased by 9.2% [95% credible interval (CI), 13.1-5.6%]. The largest reductions in mortality occurred in patients without need for organ support (9.6%) and in those with need for mechanical ventilation (MV) only (11%). Smallest reductions occurred in patients requiring MV, vasopressors, and dialysis (3.9%) simultaneously. Survival gains over time decreased as PS worsened. Lung cancer patients had the lowest decrease in mortality. Each year was associated with a lower sub-hazard for ICU death [SHR 0.93 (0.91-0.94)] and a higher chance of being discharged alive from the ICU earlier [SHR 1.01 (1-1.01)]. CONCLUSION: Outcomes in critically ill cancer patients improved in the past 8 years, with reductions in both mortality and ICU LOS, suggesting improvements in overall care. However, outcomes remained poor in patients with lung cancer, requiring multiple organ support and compromised PS.

Metabolic acidosis in patients with severe sepsis and septic shock: a longitudinal quantitative study.

OBJECTIVE: To describe the composition of metabolic acidosis in patients with severe sepsis and septic shock at intensive care unit admission and throughout the first 5 days of intensive care unit stay. DESIGN: Prospective, observational study. SETTING: Twelve-bed intensive care unit. PATIENTS: Sixty patients with either severe sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were collected until 5 days after intensive care unit admission. We studied the contribution of inorganic ion difference, lactate, albumin, phosphate, and strong ion gap to metabolic acidosis. At admission, standard base excess was -6.69 +/- 4.19 mEq/L in survivors vs. -11.63 +/- 4.87 mEq/L in nonsurvivors (p < .05); inorganic ion difference (mainly resulting from hyperchloremia) was responsible for a decrease in standard base excess by 5.64 +/- 4.96 mEq/L in survivors vs. 8.94 +/- 7.06 mEq/L in nonsurvivors (p < .05); strong ion gap was responsible for a decrease in standard base excess by 4.07 +/- 3.57 mEq/L in survivors vs. 4.92 +/- 5.55 mEq/L in nonsurvivors with a nonsignificant probability value; and lactate was responsible for a decrease in standard base excess to 1.34 +/- 2.07 mEq/L in survivors vs. 1.61 +/- 2.25 mEq/L in nonsurvivors with a nonsignificant probability value. Albumin had an important alkalinizing effect in both groups; phosphate had a minimal acid-base effect. Acidosis in survivors was corrected during the study period as a result of a decrease in lactate and strong ion gap levels, whereas nonsurvivors did not correct their metabolic acidosis. In addition to Acute Physiology and Chronic Health Evaluation II score and serum creatinine level,inorganic ion difference acidosis magnitude at intensive care unit admission was independently associated with a worse outcome. CONCLUSIONS: Patients with severe sepsis and septic shock exhibit a complex metabolic acidosis at intensive care unit admission, caused predominantly by hyperchloremic acidosis,which was more pronounced in nonsurvivors. Acidosis resolution in survivors was attributable to a decrease in strong ion gap and lactate levels.

Daily evaluation of organ function during renal replacement therapy in intensive care unit patients with acute renal failure.

PURPOSE: The aim of this study was to assess changes in organ function in acute renal failure patients during renal replacement therapy and relate them to outcome. MATERIALS AND METHODS: Medical and nursing charts from 111 patients with acute renal failure who underwent renal replacement therapy (hemodialysis or hemofiltration) from July 2000 until July 2002 on a 31-bed medicosurgical intensive care unit (ICU) at a university hospital in Belgium and in whom the Sequential Organ Failure Assessment (SOFA) score was calculated daily before the start of therapy until the seventh day, or the end of therapy, were analyzed. Changes in SOFA score over time (Delta SOFA) were calculated. RESULTS: Of 111 patients, 63 (57%) died in the ICU. Nonsurvivors were older (68 [52-76] vs 59 [48-70] years, P = .017) and had initially higher respiratory, cardiovascular, and total SOFA scores compared with survivors. A greater Delta renal SOFA at 24 hours was associated univariantly with a higher risk of ICU mortality (odds ratio, 1.7; 95% confidence interval, 1.2-2.6; P = .013). In a multivariate analysis with ICU outcome as the dependent variable, only age, cardiovascular SOFA score on admission, and the change in total SOFA score over the first 24 hours were independently associated with a greater risk of death. CONCLUSIONS: Assessment of these factors in the first 24 hours of renal replacement therapy could help identify patients at higher risk of mortality early during their ICU admission.

Dyslipidemia: a prospective controlled randomized trial of intensive glycemic control in sepsis.

PURPOSE: Metabolic disturbances are quite common in critically ill patients. Glycemic control appears to be an important adjuvant therapy in such patients. In addition, disorders of lipid metabolism are associated with worse prognoses. The purpose of this study was to investigate the effects that two different glycemic control protocols have on lipid profile and metabolism. METHODS: We evaluated 63 patients hospitalized for severe sepsis or septic shock, over the first 72 h of intensive care. Patients were randomly allocated to receive conservative glycemic control (target range 140­180 mg/dl) or intensive glycemic control (target range 80­110 mg/dl). Serum levels of lowdensity lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, free fatty acids, and oxidized low-density lipoprotein were determined. RESULTS: In both groups, serum levels of low-density lipoprotein, high-density lipoprotein, and total cholesterol were below normal, whereas those of free fatty acids, triglycerides, and oxidized lowdensity lipoprotein were above normal. At 4 h after admission, free fatty acid levels were higher in the conservative group than in the intensive group, progressively decreasing in both groups until hour 48 and continuing to decrease until hour 72 only in the intensive group. Oxidized low-density lipoprotein levels were elevated in both groups throughout the study period. CONCLUSIONS: Free fatty acids respond to intensive glycemic control and, because of their high toxicity, can be a therapeutic target in patients with sepsis.

Potential role of poly(adenosine 5'-diphosphate-ribose) polymerase activation in the pathogenesis of myocardial contractile dysfunction associated with human septic shock.

OBJECTIVE: Sepsis is associated with increased production of superoxide and nitric oxide, with consequent peroxynitrite generation. Cardiodepression is induced in the heart during oxidative stress associated with septic shock. Oxidative and nitrosative stress can lead to activation of the nuclear enzyme poly(adenosine 5'-diphosphate [ADP]-ribose) polymerase (PARP), with subsequent loss of myocardial contractile function. The aim of the study was to investigate whether cardiodepression found in septic patients is associated with plasma markers of myocardial necrosis and with myocardial PARP activation. DESIGN: Prospective and observational study. SETTING: University hospital intensive care unit for clinical and surgical patients. PATIENTS: Twenty-five patients older than 18 yrs presenting with severe sepsis or septic shock. Patients with history of chronic heart failure, cancer, coronary artery disease, diabetes, or acquired immune deficiency syndrome were excluded. INTERVENTIONS: Patients were followed for 28 days, and biochemical and hemodynamic data were collected on days 1, 3, and 6 of sepsis. The groups were survivors and nonsurvivors, defined only after the end of clinical patient evolution. Heart sections from patients who died were analyzed with hematoxylin-eosin and Picro Sirius-Red immunostaining and with electron microscopy. MEASUREMENTS AND MAIN RESULTS: The study population included 25 individuals, of whom 12 (48%) died during the 6 days of follow-up. The initial data of the inflammation marker C-reactive protein and Acute Physiologic and Chronic Health. Evaluation severity were similar in both groups (nonsurvivors, 26 +/- 2; survivors, 24 +/- 5; NS). Overall, an increase in plasma troponin level was related to increased mortality risk. In patients who died, significant myocardial damage was detected, and histologic analysis of heart sections showed inflammatory infiltration, increased collagen deposition, and derangement of mitochondrial cristae. Immunohistochemical staining for poly(ADP-ribose) (PAR), the product of activated PARP, was demonstrated in septic hearts. There was a positive correlation between PAR staining densitometry and troponin I (r(2) = 0.73; p < .05), and the correlation of PAR staining densitometry and left ventricular systolic stroke work index was r(2) = 0.33 (p = .0509). CONCLUSION: There is significant PARP activation in the hearts of septic patients with impaired cardiac function. We hypothesize that PARP activation may be partly responsible for the cardiac depression seen in humans with severe sepsis.