Predictors of mortality in patients undergoing autologous hematopoietic cell transplantation admitted to the intensive care unit.

Between January 2001 and July 2006, 1013 patients received autologous hematopoietic cell transplants (AHCT) at Canada's largest transplant center. In this retrospective cohort study of AHCT patients admitted to the intensive care unit (ICU), we describe the outcomes following ICU admission and the variables measured in the first 24 h of ICU admission associated with overall ICU mortality. Results indicate a 3.3% ICU admission rate (n=34) with 13 deaths (1% overall mortality rate, 38% in ICU mortality rate). The worst outcome was in AL amyloid patients of whom 28% were admitted to the ICU, with an ICU mortality rate of 55%. The Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE II) score in the first 24 h were statistically associated with mortality by univariate analysis. Other variables measured at 24 h and associated with ICU mortality included multiorgan failure, mechanical ventilation, inotropic support >4 h and Gram-negative sepsis. Our data indicate that ICU admission in the autotransplant population is rare and that it is influenced by underlying diagnosis, with AL amyloid patients having the highest risk. Our observations may assist clinical decision-making regarding the continuation of intensive care delivered 24 h after ICU admission.

Practising evidence-based medicine: the design and implementation of a multidisciplinary team-driven extubation protocol.

BACKGROUND: Evidence from recent literature shows that protocol-directed extubation is a useful approach to liberate patients from mechanical ventilation (MV). However, research evidence does not necessarily provide guidance on how to implement changes in individual intensive care units (ICUs). We conducted the present study to determine whether such an evidence-based strategy can be implemented safely and effectively using a multidisciplinary team (MDT) approach. METHOD: We designed a MDT-driven extubation protocol. Multiple meetings were held to encourage constructive criticism of the design by attending physicians, nurses and respiratory care practitioners (RCPs), in order to define a protocol that was evidence based and acceptable to all clinical staff involved in the process of extubation. It was subsequently implemented and evaluated in our medical/ surgical ICU. Outcomes included response of the MDT to the initiative, duration of MV and stay in the ICU, as well as reintubation rate. RESULTS: The MDT responded favourably to the design and implementation of this MDT-driven extubation protocol, because it provided greater autonomy to the staff. Outcomes reported in the literature and in the historical control group were compared with those in the protocol group, and indicated similar durations of MV and ICU stay, as well as reintubation rates. No adverse events were documented. CONCLUSION: An MDT approach to protocol-directed extubation can be implemented safely and effectively in a multidisciplinary ICU. Such an effort is viewed favourably by the entire team and is useful in enhancing team building.

Prospective trial of high-frequency oscillation in adults with acute respiratory distress syndrome.

OBJECTIVE: To evaluate the safety and efficacy of high-frequency oscillatory ventilation (HFOV) in adult patients with the acute respiratory distress syndrome (ARDS) and oxygenation failure. DESIGN: Prospective, clinical study. SETTING: Intensive care and burn units of two university teaching hospitals. PATIENTS: Twenty-four adults (10 females, 14 males, aged 48.5 +/- 15.2 yrs, Acute Physiology and Chronic Health Evaluation II score 21.5 +/- 6.9) with ARDS (lung injury score 3.4 +/- 0.6, Pao2/Fio2 98.8 +/- 39.0 mm Hg, and oxygenation index 32.5 +/- 19.6) who met one of the following criteria: Pao2 < or =65 mm Hg with Fio2 > or =0.6, or plateau pressure > or =35 cm H2O. INTERVENTIONS: HFOV was initiated in patients with ARDS after varying periods of conventional ventilation (CV). Mean airway pressure (Paw) was initially set 5 cm H2O greater than Paw during CV, and was subsequently titrated to maintain oxygen saturation between 88% and 93% and Fio2 < or =0.60. MEASUREMENTS AND MAIN RESULTS: Fio2, Paw, pressure amplitude of oscillation, frequency, blood pressure, heart rate, and arterial blood gases were monitored during the transition from CV to HFOV, and every 8 hrs thereafter for 72 hrs. In 16 patients who had pulmonary artery catheters in place, cardiac hemodynamics were recorded at the same time intervals. Throughout the HFOV trial, Paw was significantly higher than that applied during CV. Within 8 hrs of HFOV application, and for the duration of the trial, Fio2 and Paco2 were lower, and Pao2/Fio2 was higher than baseline values during CV. Significant changes in hemodynamic variables following HFOV initiation included an increase in pulmonary artery occlusion pressure (at 8 and 40 hrs) and central venous pressure (at 16 and 40 hrs), and a reduction in cardiac output throughout the course of the study. There were no significant changes in systemic or pulmonary pressure associated with initiation and maintenance of HFOV. Complications occurring during HFOV included pneumothorax in two patients and desiccation of secretions in one patient. Survival at 30 days was 33%, with survivors having been mechanically ventilated for fewer days before institution of HFOV compared with nonsurvivors (1.6 +/- 1.2 vs. 7.8 +/- 5.8 days; p =.001). CONCLUSIONS: These findings suggest that HFOV has beneficial effects on oxygenation and ventilation, and may be a safe and effective rescue therapy for patients with severe oxygenation failure. In addition, early institution of HFOV may be advantageous.

Serial renal biopsy in systemic lupus erythematosus.

OBJECTIVE: To examine the role of sequential renal biopsies in patients with systemic lupus erythematosus (SLE), with regard to indications, morphologic change over time, and the clinical utility of repeat biopsies. METHODS: Patients with repeat renal biopsies were identified from the University of Toronto Lupus Clinic Database and their biopsies were reviewed blindly by a committee, using the WHO classification as well as activity and chronicity indices. Reasons for obtaining biopsy were documented, and therapeutic decisions following repeat biopsy were tabulated. RESULTS: Fifty-seven patients (49 F/9 M) had at least 2 renal biopsies between 1970 and 1994. The mean interval between biopsies was 4.2 years. The major reason for obtaining the first biopsy was disease diagnosis (32/57), while the majority of repeat biopsies were performed to discern the cause of increasing proteinuria (45/57). A comparison of the WHO classification of initial and repeat biopsies showed evolution to another class in 23 instances, but more commonly a change within a class was seen. A decrease in proliferative lesions (classes III and IV and subsets of V) was noted on repeat biopsies. The chronicity index increased significantly (p = 0.0001) and the activity index decreased (p = 0.064) between biopsies. Seventy-seven percent of patients had a change in treatment based on biopsy results. CONCLUSION: The major reason for repeat renal biopsy in patients with SLE was proteinuria. Renal morphology in patients with SLE can change with time, particularly in terms of chronicity and activity features. Repeat biopsies in patients with SLE appear to have clinical utility.

Effect of antimalarial agents on the fasting lipid profile in systemic lupus erythematosus.

OBJECTIVE: To ascertain the relative effect of antimalarial (AM) agents on fasting lipid fractions in patients with systemic lupus erythematosus (SLE). METHODS: The study was cross sectional including all patients with SLE who were seen in our lupus clinic with fasting lipid profiles measured as part of evaluation from November 1995 to March 1999. RESULTS: A total of 123 patients with a mean age of 45.3 years and mean disease duration 13.4 years were studied; 73.2% were taking prednisone with a mean +/- SD dose of 10.9 +/- 9.2 mg/day, 48.0% were taking AM, and 30.8% were taking both. In the entire group, patients taking AM had a 12.5% lower total cholesterol (TC) (5.11 +/- 1.27 vs 5.84 +/- 1.23; p = 0.002), 22.1% lower very low density lipid-cholesterol (VLDL-C) (0.66 +/- 0.40 vs 0.85 +/- 0.39; p = 0.01), and 15.7% lower LDL-C (3.01 +/- 1.14 vs 3.58 +/- 1.10; p = 0.007). For patients taking prednisone, those taking concomitant AM (n = 38) had significantly lower TC (5.26 +/- 1.30 vs 5.99 +/- 1.29; p = 0.01), VLDL-C (0.65 +/- 0.39 vs 0.85 +/- 0.41; p = 0.02), and LDL-C (3.05 +/- 1.20 vs 3.69 +/- 1.09; p = 0.01) than those without AM (n = 48). For patients taking < or = 10 mg/day prednisone, TC (4.69 +/- 0.88 vs 5.74 +/- 1.20; p < 0.001), VLDL-C (0.61 +/- 0.37 vs 0.83 +/- 0.44; p = 0.05), and LDL-C (2.57 +/- 0.76 vs 3.49 +/- 1.04; p < 0.001) were still lower in patients with concomitant AM (n = 22) than those without AM (n = 36). CONCLUSION: TC, VLDL-C, and LDL-C levels were significantly lower in patients taking AM, including patients taking concomitant prednisone. Thus AM may have beneficial effects in SLE in addition to disease suppression.

Natural history of hypercholesterolemia in systemic lupus erythematosus.

OBJECTIVE: To determine the natural history of hypercholesterolemia in the first 3 years of disease in an inception cohort of patients with systemic lupus erythematosus (SLE) followed at a single center and to determine the influence of hypercholesterolemia on the subsequent development of coronary artery disease (CAD) related events. METHODS: We identified patients who were seen at the University of Toronto lupus clinic within 1 year of diagnosis from January 1, 1974, to December 31, 1987, and who were seen at least once a year in the first 3 years. Patients were divided into 3 groups: Normal cholesterol: serum total cholesterol (TC) < 5.2 mmol/l throughout the 3 year period of study. Sustained hypercholesterolemia: at least one measurement of TC of > 5.2 mmol/l in each of the first 3 years at the clinic. Variable hypercholesterolemia: TC > 5.2 mmol/l in no more than 2 of the first 3 years of followup. Patients were followed from inception until the present day. The primary outcome was the time of the first CAD related event (myocardial infarction, angina, or sudden unexplained death). RESULTS: One hundred thirty-four patients (118 women, 16 men) were studied: 33 (24.6%) had normal cholesterol, 54 (40.3%) had sustained hypercholesterolemia, and 47 (35.1%) had variable hypercholesterolemia. Using multiple logistic regression the best predictors of sustained hypercholesterolemia were cumulative dose of steroids, no antimalarial therapy, and age of onset of SLE > 35 years old. CAD related events occurred in 1 (3%) of the normal TC group, 3 (6.4%) of the variable group, and in 15 (27.8%) of the sustained group (p = 0.003), 79% of all CAD events occurred in the sustained group. The best predictors of CAD were sustained hypercholesterolemia, lung involvement, and age at onset of SLE > 35 years. CONCLUSION: Within 3 years of diagnosis, 75.4% of patients with SLE had elevated TC, which was sustained in 40.3% of all patients. Older age at onset as well as increased cumulative dose of steroids and no antimalarial therapy are significant predictors of this group. It is this group that experiences the majority of CAD related events. Aggressive lipid lowering therapy should be targeted at such patients.

Extrarenal disease activity in systemic lupus erythematosus is not suppressed by chronic renal insufficiency or renal replacement therapy.

OBJECTIVE: To assess whether chronic renal impairment (CRI) and/or renal replacement therapy (RRT) in systemic lupus erythematosus (SLE) are associated with reduced extrarenal SLE activity. METHODS: This was a retrospective cohort analysis of patients with SLE who are followed at the University of Toronto Lupus Clinic. Patients with SLE were studied in 2 stages; chronic renal insufficiency (defined as a serum creatinine > 200 mumol/1 for > 6 months) and following the institution of dialysis therapy. Controls consisted of the next 2 age and sex matched patients in the clinic with a history of lupus nephritis who had not developed renal insufficiency. We assessed the flare rate (an increase in nonrenal SLEDAI > or = 1.0) for patients and controls in the first 12 months of followup at the clinic in each stage. RESULTS: Twenty-one patients, 17 female and 4 male, were followed through 25 episodes of CRI or RRT as were 50 controls. In the CRI stage (n = 12), flares occurred in 8 (67%) within one year compared to 14 (58%) of 24 controls (p = NS). In the RRT stage (n = 13), flares occurred in 7 (54%) compared to 16 (62%) of 26 controls (p = NS). The magnitude as well as the characteristics of the flares did not differ between patients and controls in either stage. CONCLUSION: Patients with SLE who develop CRI, or who receive RRT, continue to display evidence of ongoing extrarenal disease activity. Such patients require careful longterm followup for management of their extrarenal disease.

Factors associated with fatigue in patients with systemic lupus erythematosus.

OBJECTIVE: To examine the relation between fatigue, disease activity, damage, and quality of life measures in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive patients attending the University of Toronto Lupus Clinic were studied. Disease activity was assessed using the SLEDAI and SLAM-R and damage using the SLICC/ACR Damage index. Fatigue was measured by the Fatigue Severity Score (FSS) and health status by the SF-36 questionnaire. In all cases a tender point count was also performed. RESULTS: 81 patients were studied. Their mean (SD) age and disease duration were 43 (12.5) years and 12.7 (8.0) years respectively. The FSS did not correlate with the SLEDAI nor with the SLAM-R. There was no correlation with the SLICC damage index. Fatigue severity correlated with the tender point count (SCC r=0.46, p<0.001), and negatively with all domains of the SF36 (r values -0.50 to -0.82). Disease activity and damage accounted for only 4.8% and 4% respectively of the variance in fatigue severity reported by patients. CONCLUSION: In an outpatient population of SLE patients, fatigue severity correlates with poor health status and a higher tender point count. In patients with SLE, factors associated with quality of life and fibromyalgia seem to have a greater influence on the severity of reported fatigue than does the level of current disease activity.