The Dose Response Multicentre Investigation on Fluid Assessment (DoReMIFA) in critically ill patients.

BACKGROUND: The previously published "Dose Response Multicentre International Collaborative Initiative (DoReMi)" study concluded that the high mortality of critically ill patients with acute kidney injury (AKI) was unlikely to be related to an inadequate dose of renal replacement therapy (RRT) and other factors were contributing. This follow-up study aimed to investigate the impact of daily fluid balance and fluid accumulation on mortality of critically ill patients without AKI (N-AKI), with AKI (AKI) and with AKI on RRT (AKI-RRT) receiving an adequate dose of RRT. METHODS: We prospectively enrolled all consecutive patients admitted to 21 intensive care units (ICUs) from nine countries and collected baseline characteristics, comorbidities, severity of illness, presence of sepsis, daily physiologic parameters and fluid intake-output, AKI stage, need for RRT and survival status. Daily fluid balance was computed and fluid overload (FO) was defined as percentage of admission body weight (BW). Maximum fluid overload (MFO) was the peak value of FO. RESULTS: We analysed 1734 patients. A total of 991 (57 %) had N-AKI, 560 (32 %) had AKI but did not have RRT and 183 (11 %) had AKI-RRT. ICU mortality was 22.3 % in AKI patients and 5.6 % in those without AKI (p < 0.0001). Progressive fluid accumulation was seen in all three groups. Maximum fluid accumulation occurred on day 2 in N-AKI patients (2.8 % of BW), on day 3 in AKI patients not receiving RRT (4.3 % of BW) and on day 5 in AKI-RRT patients (7.9 % of BW). The main findings were: (1) the odds ratio (OR) for hospital mortality increased by 1.075 (95 % confidence interval 1.055-1.095) with every 1 % increase of MFO. When adjusting for severity of illness and AKI status, the OR changed to 1.044. This phenomenon was a continuum and independent of thresholds as previously reported. (2) Multivariate analysis confirmed that the speed of fluid accumulation was independently associated with ICU mortality. (3) Fluid accumulation increased significantly in the 3-day period prior to the diagnosis of AKI and peaked 3 days later. CONCLUSIONS: In critically ill patients, the severity and speed of fluid accumulation are independent risk factors for ICU mortality. Fluid balance abnormality precedes and follows the diagnosis of AKI.

'Pulse oral' versus intravenous calcitriol therapy in chronic hemodialysis patients. A prospective and randomized study.

The aim of this prospective and randomized study was to compare the efficacy, side effects, and costs of 'pulse oral' versus intravenous calcitriol in the treatment of secondary hyperparathyroidism in hemodialysis (HD) patients. A total of 20 patients were randomized to receive over a 4-month period pulse orally administered calcitriol (pulse oral group; n = 10) or intravenous calcitriol (intravenous group; n = 10). All patients used standard dialysate calcium (1.75 mmol/l) throughout the study period. In accordance with the study design calcium dialysate concentrations were reduced when this was necessary to avoid hypercalcemic crises. The patients were stratified into two subgroups according to their initial serum PTH levels: patients with mild or moderate degree of hyperparathyroidism (17 patients) and patients with severe hyperparathyroidism (3 patients). Intravenous and pulse oral cacitriol did not significantly reduce serum PTH concentrations in patients with severe hyperparathyroidism (1,157 +/- 156 vs. 807 +/- 228 pg/ml [corrected], p = 0.09). Intermittent calcitriol, administered by intravenous or oral route, significantly reduced serum PTH levels (326 +/- 119 vs. 109 +/- 79 pg/ml [corrected], p = 0.0001) in patients with mild or moderate hyperparathyroidism. In patients with mild or moderate hyperparathyroidism, intravenous calcitriol significantly reduced PTH concentrations at the end of the 1st month, before the increase of serum ionized calcium levels, whereas 'pulse oral' calcitriol significantly suppressed parathyroid activity at the end of the 2nd month. Calcium dialysate concentration was reduced in 9 out of 10 (90%) patients of the pulse oral group and in all patients (10/10) of intravenous group. The incidence of hypercalcemic crises was 24% (39/160) in the pulse oral group and 14% (27/160) in the intravenous group. Analysis of costs showed that intravenous calcitriol was more expensive compared to pulse oral calcitriol. These data indicate that intermittent intensive calcitriol therapy, regardless of the route of administration, is effective in suppressing parathyroid activity in HD patients with mild or moderate hyperparathyroidism. In contrast, intermittent calcitriol therapy has a limited ability to achieve sustained serum PTH reductions in HD patients with severe hyperparathyroidism. Intravenous calcitriol was more expensive than pulse oral calcitriol, and we recommend the use of pulse oral calcitriol in HD patients with mild or moderate secondary hyperparathyroidism.

Recombinant hepatitis B vaccine use in chronic hemodialysis patients. Long-term evaluation and cost-effectiveness analysis.

The prevalence of hepatitis B virus (HBV) infection in our unit was 45% (86/190); there were 77 (40.5%) and 9 (4.7%) patients with previous and persistent HBV infection, respectively. Recombinant hepatitis B vaccine was given to 118 chronic HD patients with a regimen of 3 double doses administered intramuscularly at 0, 1 and 2 months, obtaining a seroprotection rate of 67% (79/118), 57% (45/79) being high responders. At month 24, 78% (40/51) maintained protective levels of anti-HBs, 45% (18/40) of them being high responders. There was a statistically significant difference between responder and non-responder patients with regard to nutritional parameters such as serum total proteins and mean levels of transferrinemia. The number of diabetic patients was significantly increased in the nonresponder group. Patients with persistent antibodies ('persistent responders') were younger and had a shorter duration of HD treatment compared to those responders who rapidly lost anti-HBs ('transient responders'). Serological positivity for antibodies against hepatitis B core antigen significantly facilitates the decrease of anti-HBs antibodies over time. We detected seven episodes of HBV infection among HD patients at our unit before the beginning of the vaccination program. On the contrary, there were no episodes of HBV infection among responder vaccinees during the 24-month follow-up period. After the initial cost of vaccination, a savings of US$ 3,272 per year was realized by the elimination of frequent serologic screening of vaccine responders.