Withdrawal of life-sustaining treatment in a mixed intensive care unit: most common in patients with catastropic brain injury.

OBJECTIVE: To determine the incidence of withdrawal of life-sustaining treatment in various groups of patients in a mixed intensive care unit (ICU). DESIGN: Observational retrospective. SETTING: University hospital mixed medical, neurological, neurosurgical and surgical ICU. PATIENTS: All patients admitted to the ICU between 1 November 2006, and 31 October 2007. RESULTS: 1,353 Patients were admitted to our ICU between 1 November 2006, and 31 October 2007. During this period, 218 (16.1%) patients died in the ICU, 10 of which were excluded for further analysis. In 174 (83.7%) of the remaining 208 patients, life-sustaining treatment was withdrawn. Severe CNS injury was in 86 patients (49.4%) being the reason for withdrawal of treatment, followed by MODS in 67 patients (38.5%). Notably, treatment was withdrawn in almost all patients (95%) who died of CNS failure. Patients who died in the ICU were significantly older, more often admitted for medical than surgical reasons, and had higher SOFA and APACHE II scores compared with those who survived their ICU stay. Also, SOFA scores before discharge/death were significantly different from admission scores. Of the 1,135 patients who survived their ICU stay, only 51 patients (4.5%) died within 28 days after ICU discharge. CONCLUSIONS: In 83, 7% of patients who die in the mixed ICU life-sustaining treatment is withdrawn. Severe cerebral damage was the leading reason to withdraw life-sustaining treatment.

The effects of chronic kidney disease and renal replacement therapy on circulating dendritic cells.

BACKGROUND: The mechanisms underlying the immunodeficiency of chronic kidney disease (CKD) are incompletely understood. Recently, we described decreased numbers of myeloid (m) and plasmacytoid (p) dendritic cells (DCs), considered the most important antigen-presenting cells, in peripheral blood of patients on chronic intermittent haemodialysis (CIHD). In this study, we analysed whether this reduction resulted from CKD or from renal replacement therapy (RRT). METHODS: Using flowcytometry, we quantified mDCs and pDCs in peripheral blood of patients maintained on CIHD (n = 37), continuous ambulatory peritoneal dialysis (CAPD; n = 29), and patients with CKD not receiving RRT (n = 37). Twenty-nine healthy volunteers served as controls. RESULTS: Patients with CKD (n = 103) had lower pDC and mDC counts compared with volunteers: 4.2 vs 8.3 and 10.0 vs 13.8 x 10(6) cells/l, respectively (P < or = 0.001). Within the CKD group, pDC counts did not differ between patients on CIHD, CAPD and those not receiving RRT (3.6 vs 5.0 vs 4.9 x 10(6) cells/l, respectively). In the latter group, pDC numbers correlated with the glomerular filtration rate (GFR; Spearman's r = 0.49; P<0.01). In contrast, mDC counts of patients on CIHD were lower compared with patients on CAPD (7.5 vs 10.1 x 10(6) cells/l; P = 0.039) and patients not receiving RRT (13.7 x 10(6) cells/l; P<0.001). Among non-dialyzing patients, no correlation existed between GFR and mDC numbers, which were comparable to those of volunteers, even when only non-dialyzing patients with a GFR below 15 ml/min were analysed. CONCLUSIONS: Circulating DC counts are decreased in patients with CKD; for pDCs, this reduction is primarily related to the loss of GFR, whereas the dialysis treatment appears to affect mDC numbers.

Peripheral blood dendritic cells and GM-CSF as an adjuvant for hepatitis B vaccination in hemodialysis patients.

BACKGROUND: Dysfunctional antigen presentation may underlie the impaired antibody response to hepatitis B vaccination in hemodialysis patients. Dendritic cells are considered to be the most important antigen presenting cells, but their presence and function in hemodialysis patients is unclear. Granulocyte-monocyte-colony stimulating factor (GM-CSF) has been given successfully to hemodialysis patients to increase the proportion of responders to hepatitis B vaccination. Although GM-CSF acts on both monocytes and dendritic cells, the mechanisms underlying its adjuvant quality are largely unknown. METHODS: In this study we analyzed monocytes and dendritic cells in the peripheral blood of hemodialysis patient that had responded to a standard hepatitis B vaccination procedure (responders), patients who had not responded (nonresponders), and healthy controls. The nonresponders were given two additional booster vaccines, both preceded by administration of GM-CSF the day before. RESULTS: After two booster vaccinations with GM-CSF, six out of seven patients developed a protective antibody response to hepatitis B. The memory T-cell response to tetanus toxoid was significantly lower in nonresponders compared to controls. The monocytes of dialysis patients and healthy controls showed a similar expression of relevant cell surface molecules. However, the numbers of circulating dendritic cells were on average 50% reduced compared to healthy controls, with a further reduction after GM-CSF administration. This was accompanied by a decrease of T-cell proliferation in antigen presentation assays. Monocytes showed increased major histocompatibility complex (MHC) class II, CD54, and CD40 expression, while their antigen-presenting capacity remained unchanged. CONCLUSION: GM-CSF is an effective adjuvant for hepatitis B vaccination in primary nonresponding hemodialysis patients, but paradoxically decreases the antigen presenting capacity of peripheral blood mononuclear cells and the number of circulating dendritic cells.