Comparative study of three methods of estimation of creatinine clearance in critically ill patients

Background

At the bedside, the reference method for creatinine clearance determination is based on the measurement of creatinine concentrations in urine and serum (mCrCl). Several models are available to calculate the creatinine clearance from the serum creatinine concentration. This observational survey aimed at testing the hypothesis that the proposed equations are unreliable to determine accurate creatinine clearance in patients admitted to intensive care unit (ICU).

Method

Creatinine clearance was determined by the use of mCrCl. Then, we compared three equations: Cockcroft-Gault (CG), Simplified Modification of Diet in Renal Disease (MDRDs), and Chronic Kidney Disease Epidemiology (CKD-EPI) in 156 consecutive patients within the first 24 hours after ICU admission. We tested the hypothesis that the three equations were equivalent. The agreement between the three equations was evaluated by linear regression and Bland and Altman analysis.

Results

Bland and Altman analysis showed similar agreement between the three equations. The biases and precisions were –4.8 ± 51, –1.3 ± 50, and 8.2 ± 44 for CG, MDRDs, and CKD-EPI equations, respectively (P > 0.05). The precisions were similar for the three equations (P > 0.05). The percentages of outliers at ± 30% were 44%, 45%, and 49% for CG, MDRDs, and CKD-EPI, respectively (P > 0.05).

Conclusion

Regarding the high percentage of outliers, the use of these equations cannot be recommended in ICU patients.     

Impact of a goal-directed therapy protocol on postoperative fluid balance in patients undergoing liver transplantation: A retrospective study

Objective

Liver transplantation carries major risks during the perioperative period. Few studies focused on the hemodynamics of patients undergoing liver transplantation. The present study was aimed to evaluate the impact of the implementation of a protocol including goal-directed therapy in patients undergoing liver transplantation. Our first goal was to determine its impact on the fluid balance. Secondarily, we evaluated possible improvements in the patient outcomes.

Study design

A before and after study.

Patients and methods

Fifty patients undergoing liver transplantation were included during two successive six-month periods. During the first period, the management of the patients was left at the discretion of the senior physicians (control group, n = 25). During the second period, the patients were treated according to a predetermined protocol including a specific hemodynamic monitoring (protocol group, n = 25).

Results

The fluid balance was negative in the protocol group and positive in the control group at 24 h (−606 mL vs. +3445 mL, P < 0.01) and 48 h (−2315 mL vs. +1170 mL, P < 0.01) after liver transplantation. The volume of the crystalloid administration was lower in the protocol group than in the control group (5000 mL vs. 8000 mL, P < 0.01, and 1500 mL vs. 6000 mL, P < 0.01, during surgery and 48 h after liver transplantation, respectively). The duration of mechanical ventilation and postoperative ileus were significantly reduced in the protocol group, as compared with the control group, 20 h vs. 94 h (P < 0.01) and 4 days vs. 6 days (P < 0.01), respectively.

Conclusion

For patients undergoing liver transplantation, the implementation of a protocol aiming to optimize hemodynamics was associated with reduced fluid balance and decreased requirement for mechanical ventilation and postoperative ileus duration.     

Role of preoperative carbohydrate loading: a systematic review

INTRODUCTION

Surgical stress in the presence of fasting worsens the catabolic state, causes insulin resistance and may delay recovery. Carbohydrate rich drinks given preoperatively may ameliorate these deleterious effects. A systematic review was undertaken to analyse the effect of preoperative carbohydrate loading on insulin resistance, gastric emptying, gastric acidity, patient wellbeing, immunity and nutrition following surgery.

METHODS

All studies identified through PubMed until September 2011 were included. References were cross-checked to ensure capture of cited pertinent articles.

RESULTS

Overall, 17 randomised controlled trials with a total of 1,445 patients who met the inclusion criteria were identified. Preoperative carbohydrate drinks significantly improved insulin resistance and indices of patient comfort following surgery, especially hunger, thirst, malaise, anxiety and nausea. No definite conclusions could be made regarding preservation of muscle mass. Following ingestion of carbohydrate drinks, no adverse events such as apparent or proven aspiration during or after surgery were reported.

CONCLUSIONS

Administration of oral carbohydrate drinks before surgery is probably safe and may have a positive influence on a wide range of perioperative markers of clinical outcome. Further studies are required to determine its cost effectiveness.     

α1-Adrenergic receptor antagonists and gynecomastia. A case series from the Italian spontaneous reporting system and VigiBase™

Purpose

The aim of this study was to analyze the cases of gynecomastia associated with α_1A-adrenergic receptor antagonists (α₁-ARAs) in the Italian spontaneous reporting system database (Rete Nazionale di Farmacovigilanza or RNF) and in the World Health Organization ICSRs database (VigiBase^?), focusing on tamsulosin use.

Methods

We analyzed the spontaneous reports of gynecomastia related to the use of α₁-ARAs and collected from the RNF and from VigiBase^? up to December 2012. Cases of gynecomastia have been defined as reports associated with gynecomastia according with Medical Dictionary for Regulatory Activities (MedDRA). Reporting odds ratio (ROR) and Information Component (IC) were calculated as measures of disproportionality in RNF and VigiBase^?, respectively.

Results

Up to December 2012, about 186,000 reports were recorded in the RNF. Among these, 902 reports of adverse drug reaction (ADR) have been associated with the use of at least one α₁-ARAs. Of these, in 15 cases, gynecomastia was a listed ADR: in 10, the suspected drug was tamsulosin (in eight, it was the sole suspect); in two, doxazosin and alfuzosin, respectively; and in one, terazosin. ROR for tamsulosin was 5.3 (95 % CI 1.8, 15.7). In VigiBase^?, 84 reports of gynecomastia indicated tamsulosin as suspected drug. Tamsulosin-associated gynecomastia showed the highest IC value within this class of drugs (IC 95 % 2.43).

Conclusion

In this study, we highlight a possible association between gynecomastia and tamsulosin use. To our knowledge, this association has not been described before and could represent a potential signal.     

Oxidative stress/reactive metabolite gene expression signature in rat liver detects idiosyncratic hepatotoxicants

Previously we reported a gene expression signature in rat liver for detecting a specific type of oxidative stress (OS) related to reactive metabolites (RM). High doses of the drugs disulfiram, ethinyl estradiol and nimesulide were used with another dozen paradigm OS/RM compounds, and three other drugs flutamide, phenacetin and sulindac were identified by this signature. In a second study, antiepileptic drugs were compared for covalent binding and their effects on OS/RM; felbamate, carbamazepine, and phenobarbital produced robust OS/RM gene expression. In the present study, liver RNA samples from drug-treated rats from more recent experiments were examined for statistical fit to the OS/RM signature. Of all 97 drugs examined, in addition to the nine drugs noted above, 19 more were identified as OS/RM-producing compounds—chlorpromazine, clozapine, cyproterone acetate, dantrolene, dipyridamole, glibenclamide, isoniazid, ketoconazole, methapyrilene, naltrexone, nifedipine, sulfamethoxazole, tamoxifen, coumarin, ritonavir, amitriptyline, valproic acid, enalapril, and chloramphenicol. Importantly, all of the OS/RM drugs listed above have been linked to idiosyncratic hepatotoxicity, excepting chloramphenicol, which does not have a package label for hepatotoxicity, but does have a black box warning for idiosyncratic bone marrow suppression. Most of these drugs are not acutely toxic in the rat. The OS/RM signature should be useful to avoid idiosyncratic hepatotoxicity of drug candidates.     

Lymph node blast crisis in chronic myeloid leukemia mimicking T-immunoblastic lymphoma.

BACKGROUND: Chronic myeloid leukemia arises from a somatic mutation in a pluripotent stem cell. It generally terminates with a blastic crisis (BC). One third of BC are lymphoid, and most have a pre-B phenotype. Few cases of T-lymphoid BC have been reported. Here we describe a lymph node blast crisis mimicking T-immunoblastic lymphoma. METHODS: Bone marrow and lymph nodes were histologically examined by standard methods and by an immunoperoxidase technique. Cytogenetic studies were also performed on lymph node and blood cells. Analysis of T-cell receptor genes and BCR rearrangements were performed on DNA extracted from both frozen bone marrow and lymph-node cells. RESULTS: Lymph-node histology showed an infiltration by large lymphoid blasts, consistent with a diagnosis of immunoblastic lymphoma. Blast cells were CD2, CD7, TDT positive, and negative for myeloid and mature lymphoid antigens. The Ph1 chromosome was found in both bone marrow and lymph-node cells. BCR rearrangement was found in the DNA from both bone marrow and lymph-node cells. TCR genes were not rearranged. DISCUSSION: The present study provides strong evidence that the lymph-node blast crisis of CML can assume the morphological appearance of immunoblastic lymphoma and may retain the immunological phenotype and genetic features of early T cells with BCR rearrangements.     

Transforming growth factor-beta trans-modulates the expression of colony stimulating factor receptors on murine hematopoietic progenitor cell lines

Transforming growth factor beta (TGF-beta) is a potent and selective growth inhibitor of early hematopoietic progenitors and leukemic cells. The cellular mechanism(s) underlying this antiproliferative effect is, however, currently unknown. In the present study, we demonstrate that TGF-beta inhibits the expression of granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 3 (IL-3), and granulocyte-CSF (G-CSF) receptors on murine factor-dependent and independent hematopoietic progenitor cell lines without a significant change in receptor affinity. A maximum reduction in GM-CSF receptor numbers of 65% to 77% was observed by 96-hour incubation with TGF-beta. The TGF- beta induced trans-down-modulation of GM-CSF receptors was prolonged, noncytotoxic but reversible, and not due to endogenous production of GM- CSF. The TGF-beta induced reduction in CSF receptor numbers preceded TGF-beta's growth inhibitory action. In addition, the ED50 (1 to 10 pmol/L) for TGF-beta's CSF receptor modulatory and antiproliferative effect was similar. The effect of TGF-beta on cell surface CSF receptor expression was specific, because the expression of other cell surface proteins (Ly 5 and Ly 17) was not affected by TGF-beta treatment, and because other growth inhibitors (tumor necrosis factor and interferon) did not affect CSF receptor expression. These data suggest that the downregulation of the growth of hematopoietic progenitor cells by TGF- beta involves reducing the cell surface expression on growth factor receptors.