Trueness assessment of routine electrolytes measuring systems using the candidate reference method by ion chromatography.

Electrolytes for sodium, potassium, magnesium, and calcium are important serum ions that are frequently assayed in clinical laboratories. In this study, we assessed the trueness of routine analytical systems for four cations using an inexpensive candidate reference method aimed to promote the standardization of serum electrolyte detection. An ion chromatography (IC) method with Cesium as an internal standard was developed and evaluated. The residual clinical serum samples at Chaoyang Hospital were collected and prepared into three human serum pools of electrolytes, which were used for the trueness evaluation of five routine analytical systems. Furthermore, the agreement between routine methods and the IC method was verified using 40 individual human samples. The recovery rates of sodium, potassium, magnesium and calcium were 99.69%, 100.34%, 100.43% and 99.89%, respectively. The intra-batch standard deviation and intra-laboratory precision of NIST SRM 956c were all less than 1% for the four ions. The certified values were within the validation range, and the deviation between the results and the certified values were less than 0.5%. The three serum pools were homogeneous and stable. All routine systems aligned with the IC method for four cations and achieved the analytical quality specifications for potassium and magnesium at 3 different concentrations. The developed IC method is simple, practical, accurate, and precise, which can be used as a candidate reference method for serum electrolytes measurement. Five routine analytical systems for electrolytes measurement had the acceptable bias for potassium and magnesium and their results showed good concordance.

Assessment of serum electrolytes and kidney function test for screening of chronic kidney disease among Ethiopian Public Health Institute staff members, Addis Ababa, Ethiopia.

BACKGROUND: Chronic kidney disease (CKD), which is characterized by its asymptomatic nature until an end stage, is one of the most common public health problems in the world. Thus, a regular checkup, especially for those individuals with high risk groups is inevitably important, and the screening has been done with laboratory findings. However, in developing countries, including Ethiopia screening for CKD are rarely done, and it is becoming common to hear sudden death from the kidney failure. Therefore, we aimed to screen serum electrolyte levels and estimated glomerular filtration rate (eGFR) among Ethiopian Public Health Institute (EPHI) staff members for an early detection of CKD and to identify the factors associated with it. METHODS: A cross-sectional study was conducted from July 1 to October 28, 2018 among EPHI staff members. The level of serum creatinine and electrolytes were measured using COBAS 6000 analyzer. Then, eGFR was calculated using MDRD and CKD-EPI equations. Data analysis were done using SPSS version 20, and the factors associated with the outcome variable were assessed using logistic regression. P values < 0.05 were considered as statistically significant. RESULTS: This study found that 3.6 and 1.9% of the study participants were at CKD stage II by MDRD and CKD-EPI equations, respectively. Out of the total study participants, 9.5% had hyperkalemia (serum potassium level > 5.0 mmol/L) and 8.5% had hypocalcemia (serum calcium level < 2.15 mmol/L). An older age (P = 0.006), high BMI (P = 0.045) and previous history of CVDs (P = 0.033) were found to be significantly associated factors with reduced glomerular filtration rate. Nine percent of the study participants were obese, 6.1% had family history of kidney failure, 18% self-reported history of hypertension, 3.4% diabetic and 5.3% had CVDs. About 51.2% of the study participants were males, and the majorities, (66%) of the study participants were found to be alcohol consumers. CONCLUSIONS: The prevalence of a stage II kidney disease was relatively low and none of the participants was under serious kidney disease (GFR < 60 mmol/min/1.73m2). An older age, high BMI and previous history of CVDs were significantly associated with reduced GFR. Hyperkalemia and hypokalemia were the major electrolyte disorders in the study participants.

Behavioural patterns of electrolyte repletion in intensive care units: lessons from a large electronic dataset.

Repletion of electrolytes often depends on provider-specific behavior and hospital policy. We examined the pattern of electrolyte repletion across several intensive care units (ICU) in a large healthcare system from 2010-2015. This included 109 723 potassium repletions, 51 833 magnesium repletions, 2 306 calcium repletions, 8 770 phosphate repletions, and 3 128 249 visit-days over 332 018 visits. Potassium, magnesium, and calcium were usually repleted within the institutional reference range. In contrast, the bulk of phosphate repletion was done with pre-repletion serum level below the reference range. The impact of repletion on post-repletion levels was significant but uniformly small. The pre-repletion serum level had a significant inverse correlation with the post-repletion level of each electrolyte. Potassium, magnesium and phosphate follow-up labs were scheduled in 9-10 hours after their repletion. In contrast, calcium was rechecked in less than 20 minutes. Routine repletion of potassium, magnesium and calcium had no effect on the incidence of tachyarrhythmias. We estimated the expense from electrolyte repletion within the reference range was approximately $1.25 million. Absent a specific clinical indication, repleting electrolytes when the serum concentration are within normative values may represent an avenue for cost savings, staff burden unload and potential reduction in frequency of complications in the ICUs.

Efficacy of serum blood urea nitrogen, creatinine and electrolytes in the diagnosis and mortality risk assessment of patients with acute coronary syndrome.

BACKGROUND: Although blood urea nitrogen (BUN), creatinine (Cr) and electrolytes are not the mainstay of diagnosis in acute coronary syndrome (ACS) patients but they may have a role in providing a more detailed view of the complications and mortality rates. The aim of this study was to determine the efficacy of these parameters in the diagnosis and mortality risk-assessment of patients with ACS. METHODOLOGY: A total of 200 patients with ACS were recruited in this prospective study. The relationship of serum BUN, Cr and electrolytes with cardiac enzymes, Global Registry of Acute Coronary Events (GRACE) and mortality was assessed during a 6-months follow-up. Statistical test like multivariate linear regression and binary logistic regression analysis were applied. RESULTS: On multivariate linear regression analysis, serum potassium (K) (Unstandardized Coefficient B=-3.77; p=0.04) showed significant negative association with Creatine Kinease and serum BUN (Unstandardized Coefficient B=0.52; p=0.001) showed significant positive association with Troponin I. The patients with GRACE>105 had significantly higher levels of serum BUN and Cr. Receiver operating characteristic curves showed that area under curve (AUC) of BUN (0.7) was higher than AUC of Cr (0.5). Multiple adjusted model showed that patients with BUN>32.5mg/dl were almost 20 times more likely to be associated with mortality as compared to reference group. CONCLUSION: In addition to cardiac enzymes, K along with BUN and Cr may serve as important aid in diagnosis of ACS. BUN and Cr may also serve as important tools in mortality-risk assessment of ACS patients.

Assessment of cabozantinib treatment on QT interval in a phase 3 study in medullary thyroid cancer: evaluation of indirect QT effects mediated through treatment-induced changes in serum electrolytes.

PURPOSE: This study evaluated factors impacting QTc interval in a phase 3 trial of cabozantinib in progressive, metastatic, medullary thyroid cancer (MTC). METHODS: Electrocardiogram (12-lead ECG) measurements were obtained at screening, and at pre-dose, and 2, 4, and 6 h post-dose on Days 1 and 29 in a phase 3 study in patients with MTC treated with cabozantinib (140 mg/day). Central tendency analyses were conducted on baseline-corrected QTc values. Linear and nonlinear mixed-effects models were used to evaluate potential factors affecting the QTc interval, including serum electrolytes, patient demographics, and cabozantinib concentration. RESULTS: Central tendency analysis showed that oral cabozantinib (140 mg/day) produced a 10-15 ms increase in delta-delta Fridericia corrected QT (∆∆QTcF) and delta-delta study-specific corrected QT (∆∆QTcS) on Day 29, but not on Day 1. Further analysis showed that QTcS provided a slightly more accurate QT correction than QTcF. Mixed-effects models evaluating serum electrolytes, age, sex, and cabozantinib concentration showed that decreased serum calcium and potassium could explain the majority of cabozantinib treatment-associated QTcS prolongation observed in this study. CONCLUSIONS: Cabozantinib treatment prolongs the ∆∆QTcF interval by 10-15 ms. There was the absence of a strong relationship between cabozantinib concentration and QTcS prolongation. Cabozantinib treatment effects on serum calcium and potassium best explain the QTcS prolongation observed in this study.

Does fluid resuscitation with balanced solutions induce electrolyte and metabolic abnormalities? An in vitro assessment.

BACKGROUND: Popular intravenous fluids in clinical use may have an impact on electrolyte concentration and metabolic balance and should be considered as powerful pharmacological agents. There is a growing body of evidence that fluid therapy should be more individualised and preferably based on balanced solutions. AIM: We sought to investigate the impact of three commonly used balanced fluids on electrolytes and metabolic equilibrium in an in vitro setting. METHODS: Study group comprised 32 healthy male volunteers (without history of any acute/chronic disorder or known metabolic abnormality), aged 21-35 (29 ± 4) years, weight 59-103 (81.2 ± 9.8) kg, from whom blood samples were withdrawn. The whole blood was diluted in 4:1 ratio with the study solutions to make an end-concentration of 20 vol.% of each solution. The test solutions included balanced crystalloid (Plasmalyte®, Baxter, Poland [PL]), succinylated gelatin (Geloplasma®, Fresenius Kabi, Poland [GEL]) and 6% HES 130/0.4 (Volulyte®, Fresenius Kabi, Poland [HES]). RESULTS: All fluids caused comparable degree of haemodilution. PL and GEL decreased (104 mmol/L, interquartile range [IQR] 103-105; and 106 mmol/L, IQR 105-107.5, respectively), whereas HES increased the concentration of Cl- to 109 (IQR 108-110) mmol/L. PL and HES decreased (136, IQR 136-137 mmol/L; and 138 mmol/L, IQR 137-139, respectively), whereas GEL increased the Na+ level to 140.5 (IQR 140-141) mmol/L. PL and HES decreased osmolality (277.2 mOsm/kg, IQR 275.7-278.4; and 280.9 mOsm/kg, IQR 279.3-282.0, respectively). GEL increased it to 285.7 (IQR 283.7-286.8) mOsm/kg. All test solutions caused a similar statistically significant (p < 0.05) drop in base excess and bicarbonate concentration, and these fell outside the reference values. Due to its composition, GEL caused a significant increase in lactate concentration. HES and GEL caused a statistically significant drop in strong ion difference value. Due to high lactate level, the effect of GEL was most pronounced. CONCLUSIONS: Balanced intravenous solutions should be safe in terms of their impact on human plasma electrolyte and meta-bolic equilibrium when administered to replace up to 20% of blood volume. In metabolic acidosis, balanced succinylated gelatin should be used with caution. Therefore, arterial blood gas analysis should be performed in patients in whom significant amounts of fluid are administrated, preferably with assessment of Cl-, Na+, lactate concentrations as well as pH, osmolality, and strong ion difference.

Assessment of serum trace elements and electrolytes in children with childhood and atypical autism.

The existing data demonstrate a significant interrelation between ASD and essential and toxic trace elements status of the organism. However, data on trace element homeostasis in particular ASD forms are insufficient. Therefore, the objective of the present study was to assess the level of trace elements and electrolytes in serum of children with childhood and atypical autism. A total of 48 children with ASD (24 with childhood and 24 with atypical autism) and age- and sex-adjusted controls were examined. Serum trace elements and electrolytes were assessed using inductively-coupled plasma mass spectrometry. The obtained data demonstrate that children with ASD unspecified are characterized by significantly lower Ni, Cr, and Se levels as compared to the age- and sex-matched controls. At the same time, significantly decreased serum Ni and Se concentrations were detected in patients with childhood autism. In turn, children with atypical autism were characterized by more variable serum trace element spectrum. In particular, atypical autism is associated with lower serum Al, As, Ni, Cr, Mn, and Se levels in comparison to the control values. Moreover, Al and Mn concentration in this group was also lower than that in childhood autism patients. Generally, the obtained data demonstrate lower levels of both essential and toxic trace elements in atypical autism group, being indicative of profound alteration of trace elements metabolism. However, further detailed metabolic studies are required to reveal critical differences in metabolic pathways being responsible for difference in trace element status and clinical course of the disease.

HEALTH AND NUTRITIONAL ASSESSMENT OF FREE-RANGING EASTERN INDIGO SNAKES (DRYMARCHON COUPERI) IN GEORGIA, UNITED STATES.

Clinical pathology and nutritional parameters are useful in evaluating and monitoring threatened and endangered wildlife populations, but reference ranges for most snake species are lacking. From 2001 to 2005, health assessments were performed on 58 eastern indigo snakes (EIS) (Drymarchon couperi) captured in the wild in southeastern Georgia, United States. Health and nutritional assessments performed included hematology, serum biochemistry, fat-soluble vitamins, heavy metals, pesticide contaminants, parasitology, and surveys of other pathogens. Significant differences in total solids, packed cell volume, glucose, blood urea nitrogen, albumin : globulin ratio, amylase, triglycerides, and bile acids between males and females were observed. Additionally, there was a significant difference between liver and kidney concentrations for vitamins A and E. As previously noted in captive EIS, total Ca was elevated in comparison to concentrations reported in other snake species. Parasitism was a common finding in sampled EIS, but the overall health status of this free-ranging population appeared good. A winter-time dermatitis was found in most snakes, which resolved in the summer months. This study represents the first health and nutritional assessment of free-ranging EIS, and provides needed data to guide monitoring and conservation efforts.

Energy Expenditure and Metabolic Changes of Free-Flying Migrating Northern Bald Ibis.

Many migrating birds undertake extraordinary long flights. How birds are able to perform such endurance flights of over 100-hour durations is still poorly understood. We examined energy expenditure and physiological changes in Northern Bald Ibis Geronticus eremite during natural flights using birds trained to follow an ultra-light aircraft. Because these birds were tame, with foster parents, we were able to bleed them immediately prior to and after each flight. Flight duration was experimentally designed ranging between one and almost four hours continuous flights. Energy expenditure during flight was estimated using doubly-labelled-water while physiological properties were assessed through blood chemistry including plasma metabolites, enzymes, electrolytes, blood gases, and reactive oxygen compounds. Instantaneous energy expenditure decreased with flight duration, and the birds appeared to balance aerobic and anaerobic metabolism, using fat, carbohydrate and protein as fuel. This made flight both economic and tolerable. The observed effects resemble classical exercise adaptations that can limit duration of exercise while reducing energetic output. There were also in-flight benefits that enable power output variation from cruising to manoeuvring. These adaptations share characteristics with physiological processes that have facilitated other athletic feats in nature and might enable the extraordinary long flights of migratory birds as well.

Comprehensive biometric, biochemical and histopathological assessment of nutrient deficiencies in gilthead sea bream fed semi-purified diets.

Seven isoproteic and isolipidic semi-purified diets were formulated to assess specific nutrient deficiencies in sulphur amino acids (SAA), n-3 long-chain PUFA (n-3 LC-PUFA), phospholipids (PL), P, minerals (Min) and vitamins (Vit). The control diet (CTRL) contained these essential nutrients in adequate amounts. Each diet was allocated to triplicate groups of juvenile gilthead sea bream fed to satiety over an 11-week feeding trial period. Weight gain of n-3 LC-PUFA, P-Vit and PL-Min-SAA groups was 50, 60-75 and 80-85 % of the CTRL group, respectively. Fat retention was decreased by all nutrient deficiencies except by the Min diet. Strong effects on N retention were found in n-3 LC-PUFA and P fish. Combined anaemia and increased blood respiratory burst were observed in n-3 LC-PUFA fish. Hypoproteinaemia was found in SAA, n-3 LC-PUFA, PL and Vit fish. Derangements of lipid metabolism were also a common disorder, but the lipodystrophic phenotype of P fish was different from that of other groups. Changes in plasma levels of electrolytes (Ca, phosphate), metabolites (creatinine, choline) and enzyme activities (alkaline phosphatase) were related to specific nutrient deficiencies in PL, P, Min or Vit fish, whereas changes in circulating levels of growth hormone and insulin-like growth factor I primarily reflected the intensity of the nutritional stressor. Histopathological scoring of the liver and intestine segments showed specific nutrient-mediated changes in lipid cell vacuolisation, inflammation of intestinal submucosa, as well as the distribution and number of intestinal goblet and rodlet cells. These results contribute to define the normal range of variation for selected biometric, biochemical, haematological and histochemical markers.

Assessment of the accuracy and precision of the i-Smart 30 VET Electrolyte Analyzer in dogs, cats, cattle and pigs.

BACKGROUND: Performance evaluation of point-of-care (POC) electrolyte analyzers is essential for determining their precision and accuracy in clinical practice. OBJECTIVE: The purpose of this study was to validate the i-Smart 30 VET Electrolyte Analyzer for canine, feline, bovine, and porcine samples in comparison with the ion-selective electrolyte analyzer Roche 9180 electrolyte analyzer. METHODS: A total of 400 heparinized whole blood samples were collected and analyzed by both instruments for sodium, potassium, and chloride concentrations. Within-run, between-day, and total imprecision were evaluated. Statistical analyses included tests for correlation, regression, bias, and total error. RESULTS: The coefficients of variation (CV) of both within-run and between-day imprecisions in the i-Smart 30 VET ranged from 0.4-1.6%. In addition, total CV (0.3-1.7%) and total error (0.7-3.7%) of the i-Smart 30 VET were acceptable according to the ASVCP guidelines (< 5%). The correlation between the i-Smart 30 VET and the Roche 9180 was excellent (r > .98). There was no proportional error according to the regression (slope ranges 0.92-1.00, 95% CI includes 1.00), but a constant error was detected for sodium concentration in dogs (interval = 0.5), cattle (interval = 3.0), and pigs (interval = 4.0), and for chloride concentration in cats (interval = 1.0). Most of the bias was within 95% CI, and the total error range (0.8-3.5%) was acceptable according to ASVCP guidelines. CONCLUSION: The i-Smart 30 VET Electrolyte Analyzer provides precise and accurate measurements of sodium, potassium, and chloride concentrations in whole blood samples from dogs, cats, cattle, and pigs.

Human metabolic response to systemic inflammation: assessment of the concordance between experimental endotoxemia and clinical cases of sepsis/SIRS.

INTRODUCTION: Two recent, independent, studies conducted novel metabolomics analyses relevant to human sepsis progression; one was a human model of endotoxin (lipopolysaccharide (LPS)) challenge (experimental endotoxemia) and the other was community acquired pneumonia and sepsis outcome diagnostic study (CAPSOD). The purpose of the present study was to assess the concordance of metabolic responses to LPS and community-acquired sepsis. METHODS: We tested the hypothesis that the patterns of metabolic response elicited by endotoxin would agree with those in clinical sepsis. Alterations in the plasma metabolome of the subjects challenged with LPS were compared with those of sepsis patients who had been stratified into two groups: sepsis patients with confirmed infection and non-infected patients who exhibited systemic inflammatory response syndrome (SIRS) criteria. Common metabolites between endotoxemia and both these groups were individually identified, together with their direction of change and functional classifications. RESULTS: Response to endotoxemia at the metabolome level elicited characteristics that agree well with those observed in sepsis patients despite the high degree of variability in the response of these patients. Moreover, some distinct features of SIRS have been identified. Upon stratification of sepsis patients based on 28-day survival, the direction of change in 21 of 23 metabolites was the same in endotoxemia and sepsis survival groups. CONCLUSIONS: The observed concordance in plasma metabolomes of LPS-treated subjects and sepsis survivors strengthens the relevance of endotoxemia to clinical research as a physiological model of community-acquired sepsis, and gives valuable insights into the metabolic changes that constitute a homeostatic response. Furthermore, recapitulation of metabolic differences between sepsis non-survivors and survivors in LPS-treated subjects can enable further research on the development and assessment of rational clinical therapies to prevent sepsis mortality. Compared with earlier studies which focused exclusively on comparing transcriptional dynamics, the distinct metabolomic responses to systemic inflammation with or without confirmed infection, suggest that the metabolome is much better at differentiating these pathophysiologies. Finally, the metabolic changes in the recovering patients shift towards the LPS-induced response pattern strengthening the notion that the metabolic, as well as transcriptional responses, characteristic to the endotoxemia model represent necessary and "healthy" responses to infectious stimuli.

Reducing blood testing in pediatric patients after heart surgery: a quality improvement project.

OBJECTIVES: To safely optimize blood testing and costs for pediatric cardiac surgical patients without adversely impacting patient outcomes. DESIGN: This is a quality improvement cohort project with pre- and postintervention groups. SETTING: University-affiliated pediatric cardiac ICU in a tertiary care children's hospital. PATIENTS: All patients were surgical patients for whom Risk Adjustment for Congenital Heart Surgery categories allowed for stratification by complexity. The preintervention group was treated in 2010 and the postintervention group in 2011. INTERVENTIONS: Laboratory ordering processes were analyzed, and practice changed to limit standing blood test orders and requires individualized ordering. MEASUREMENTS AND MAIN RESULTS: Three hundred nineteen patients were studied in 2010 and 345 in 2011. Groups were similar in median age, weight, length of stay (ICU length of stay), and Risk Adjustment for Congenital Heart Surgery category. There was a reduction in the total blood tests per patient (24 vs 38; p < 0.0001) and length of stay adjusted tests per patient-day (10.4 vs 14.4; p = 0.0001) in the postintervention group. The largest test reductions were blood gases and single electrolytes. Adverse outcomes, such as extubation failure (6.4% vs 5.6%), central catheter-associated bloodstream infection (2.2 vs 1.5), and hospital mortality (0.6% vs 0.6%), were not significantly different between the groups. Cost analysis demonstrated an overall laboratory cost savings of 32%. In addition, the volume of packed RBC transfusions was also significantly decreased in the postintervention group among the most complex patients (Risk Adjustment for Congenital Heart Surgery, 6). CONCLUSIONS: Blood testing rates were safely decreased in postoperative pediatric cardiac patients by changing laboratory ordering practices. In addition, packed RBC transfusion was decreased among the most complex patients.

Construction and validation of a decision tree for treating metabolic acidosis in calves with neonatal diarrhea.

BACKGROUND: The aim of the present prospective study was to investigate whether a decision tree based on basic clinical signs could be used to determine the treatment of metabolic acidosis in calves successfully without expensive laboratory equipment. A total of 121 calves with a diagnosis of neonatal diarrhea admitted to a veterinary teaching hospital were included in the study. The dosages of sodium bicarbonate administered followed simple guidelines based on the results of a previous retrospective analysis. Calves that were neither dehydrated nor assumed to be acidemic received an oral electrolyte solution. In cases in which intravenous correction of acidosis and/or dehydration was deemed necessary, the provided amount of sodium bicarbonate ranged from 250 to 750 mmol (depending on alterations in posture) and infusion volumes from 1 to 6.25 liters (depending on the degree of dehydration). Individual body weights of calves were disregarded. During the 24 hour study period the investigator was blinded to all laboratory findings. RESULTS: After being lifted, many calves were able to stand despite base excess levels below -20 mmol/l. Especially in those calves, metabolic acidosis was undercorrected with the provided amount of 500 mmol sodium bicarbonate, which was intended for calves standing insecurely. In 13 calves metabolic acidosis was not treated successfully as defined by an expected treatment failure or a measured base excess value below -5 mmol/l. By contrast, 24 hours after the initiation of therapy, a metabolic alkalosis was present in 55 calves (base excess levels above +5 mmol/l). However, the clinical status was not affected significantly by the metabolic alkalosis. CONCLUSIONS: Assuming re-evaluation of the calf after 24 hours, the tested decision tree can be recommended for the use in field practice with minor modifications. Calves that stand insecurely and are not able to correct their position if pushed require higher doses of sodium bicarbonate, if there is clinical evidence of a marked D-lactic acidosis. In those calves, determining the degree of loss of the palpebral reflex was identified as a useful decision criterion to provide an additional amount of 250 mmol sodium bicarbonate. This work demonstrates the clinical relevance of the discovery that D-lactate is responsible for most of the clinical signs expressed in neonatal diarrheic calves suffering from metabolic acidosis.

Development of a diagnostic diagram for rapid field assessment of acidosis severity in diarrheic calves.

OBJECTIVE: To develop a diagnostic diagram for rapid field assessment of acidosis severity in diarrheic calves. DESIGN: Prospective cross-sectional study. ANIMALS: 148 Piedmontese calves (38 calves in preliminary experiments; 83 diarrheic calves and 27 healthy control calves in the primary experiment). PROCEDURES: Physical examination was performed and a standard data collection form was completed for each calf. Blood samples were obtained and submitted for evaluation of acid-base balance, performance of a CBC, and measurement of electrolyte and total protein concentrations. RESULTS: Severe metabolic acidosis (extracellular base excess more negative than -10 mmol/L) was associated with abnormal mental status, delayed or absent suckle reflex, abnormal posture or gait, enophthalmos, and cold oral mucosal membranes. Clinical signs associated with severe metabolic acidosis were arranged into a grid to create a diagnostic diagram. Sensitivity and specificity of the diagnostic diagram for the prediction of severe metabolic acidosis were 88% and 79%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Use of the diagnostic diagram may aid differentiation between severe and nonsevere acidosis patterns as determined on the basis of clinical signs.

What is the value of routinely testing full blood count, electrolytes and urea, and pulmonary function tests before elective surgery in patients with no apparent clinical indication and in subgroups of patients with common comorbidities: a systematic review of the clinical and cost-effective literature.

BACKGROUND: The evidence base which supported the National Institute for Health and Clinical Excellence (NICE) published Clinical Guideline 3 was limited and 50% was graded as amber. However, the use of tests as part of pre-operative work-up remains a low-cost but high-volume activity within the NHS, with substantial resource implications. The objective of this study was to identify, evaluate and synthesise the published evidence on the clinical effectiveness and cost-effectiveness of the routine use of three tests, full blood counts (FBCs), urea and electrolytes tests (U&Es) and pulmonary function tests, in the pre-operative work-up of otherwise healthy patients undergoing minor or intermediate surgery in the NHS. OBJECTIVE: The aims of this study were to estimate the clinical effectiveness and cost-effectiveness of routine pre-operative testing of FBC, electrolytes and renal function and pulmonary function in adult patients classified as American Society of Anaesthesiologists (ASA) grades 1 and 2 undergoing elective minor (grade 1) or intermediate (grade 2) surgical procedures; to compare NICE recommendations with current practice; to evaluate the cost-effectiveness of mandating or withdrawing each of these tests in this patient group; and to identify the expected value of information and whether or not it has value to the NHS in commissioning further primary research into the use of these tests in this group of patients. DATA SOURCES: The following electronic bibliographic databases were searched: (1) BIOSIS; (2) Cumulative Index to Nursing and Allied Health Literature; (3) Cochrane Database of Systematic Reviews; (4) Cochrane Central Register of Controlled Trials; (5) EMBASE; (6) MEDLINE; (7) MEDLINE In-Process & Other Non-Indexed Citations; (8) NHS Database of Abstracts of Reviews of Effects; (9) NBS Health Technology Assessment Database; and (10) Science Citation Index. To identify grey and unpublished literature, the Cochrane Register of Controlled Trials, National Research Register Archive, National Institute for Health Research Clinical Research Network Portfolio database and the Copernic Meta-search Engine were searched. A large routine data set which recorded the results of tests was obtained from Leeds Teaching Hospitals Trust. REVIEW METHODS: A systematic review of the literature was carried out. The searches were undertaken in March to April 2008 and June 2009. Searches were designed to retrieve studies that evaluated the clinical effectiveness and cost-effectiveness of routine pre-operative testing of FBC, electrolytes and renal function and pulmonary function in the above group of patients. A postal survey of current practice in testing patients in this group pre-operatively was undertaken in 2008. An exemplar cost-effectiveness model was constructed to demonstrate what form this would have taken had there been sufficient data. A large routine data set that recorded the results of tests was obtained from Leeds Teaching Hospitals Trust. This was linked to individual patient data with surgical outcomes, and regression models were estimated. RESULTS: A comprehensive and systematic search of both the clinical effectiveness and cost-effectiveness literature identified a large number of potentially relevant studies. However, when these studies were subjected to detailed review and quality assessment, it became clear that the literature provides no evidence on the clinical effectiveness and cost-effectiveness of these specific tests in the specific patient groups. The postal survey had a 17% response rate. Results reported that in ASA grade 1, patients aged < 40 years with no comorbidities undergoing minor surgery did not have routine tests for FBC, electrolytes and renal function and pulmonary function. The results from the regression model showed that the frequency of test use was not consistent with the hypothesis of their routine use. FBC tests were performed in only 58% of patients in the data set and U&E testing was carried out in only 57%. LIMITATIONS: Systematic searches of the clinical effectiveness and cost-effectiveness literature found that there is no evidence on the clinical effectiveness or cost-effectiveness of these tests in this specific clinical context for the NHS. A survey of NHS hospitals found that respondent trusts were implementing current NICE guidance in relation to pre-operative testing generally, and a de novo analysis of routine data on test utilisation and post-operative outcome found that the tests were not be used in routine practice; rather, use was related to an expectation of a more complex clinical case. The paucity of published evidence is a limitation of this study. The studies included relied on non-UK health-care systems data, which may not be transferable. The inclusion of non-randomised studies is associated with an increased risk of bias and confounding. Scoping work to establish the likely mechanism of action by which tests would impact upon outcomes and resource utilisation established that the cause of an abnormal test result is likely to be a pivotal determinant of the cost-effectiveness of a pre-operative test and therefore evaluations would need to consider tests in the context of the underlying risk of specific clinical problems (i.e. risk guided rather than routine use). CONCLUSIONS: The time of universal utilisation of pre-operative tests for all surgical patients is likely to have passed. The evidence we have identified, though weak, indicates that tests are increasingly utilised in patients in whom there is a reason to consider an underlying raised risk of a clinical abnormality that should be taken into account in their clinical management. It is likely that this strategy has led to substantial resource savings for the NHS, although there is not a published evidence base to establish that this is the case. The total expenditure on pre-operative tests across the NHS remains significant. Evidence on current practice indicates that clinical practice has changed to such a degree that the original research question is no longer relevant to UK practice. Future research on the value of these tests in pre-operative work-up should be couched in terms of the clinical effectiveness and cost-effectiveness in the identification of specific clinical abnormalities in patients with a known underlying risk. We suggest that undertaking a multicentre study making use of linked, routinely collected data sets would identify the extent and nature of pre-operative testing in this group of patients. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Predicting hospital cost in CKD patients through blood chemistry values.

BACKGROUND: Controversy exists in predicting costly hospitalization in patients with chronic kidney disease and co-morbid conditions. We therefore tested associations between serum chemistry values and the occurrence of in-patient hospital costs over a thirteen month study period. Secondarily, we derived a linear combination of variables to estimate probability of such occurrences in any patient. METHOD: We calculated parsimonious values for select variables associated with in-patient hospitalization and compared sensitivity and specificity of these models to ordinal staging of renal disease.Data from 1104 de-identified patients which included 18 blood chemistry observations along with complete claims data for all medical expenses.We employed multivariable logistic regression for serum chemistry values significantly associated with in-patient hospital costs exceeding $3,000 in any single month and contrasted those results to other models by ROC area curves. RESULTS: The linear combination of weighted Z scores for parathyroid hormone, phosphorus, and albumin correlated with in-patient hospital care at p<0.005. ROC curves derived from weighted variables of age, eGFR, hemoglobin, albumin, creatinine, and alanine aminotransferase demonstrated significance over models based on non-weighted Z scores for those same variables or CKD stage alone. In contrast, the linear combination of weighted PTH, PO4 and albumin demonstrated better prediction, but not significance over non-weighted Z scores for PTH alone. CONCLUSION: Further study is justified to explore indices that predict costly hospitalization. Such metrics could assist Accountable Care Organizations in evaluating risk adjusted compensation for providers.

Electrolyte orders in the neuroscience intensive care unit: worth the value or waste?

BACKGROUND: To assess the value of the practice of obtaining frequent electrolyte measurements in patients with extended stay in a neuroscience intensive care unit (NICU). METHODS: We identified consecutive patients 18 years or older, admitted to the NICU between January 1 and July 31, 2009 with length of stay ≥ 5 days. We collected potassium, sodium, magnesium, ionized calcium, phosphorus laboratory measurements and hemoglobin levels, and recorded electrolyte replacement orders and red blood cell transfusions. Average laboratory costs were estimated. RESULTS: 93 patients were included in the study (54 men, mean age 54 years, range 18-85 years). Mean length of stay was 10.4 days (range 5-36 days). Sodium and potassium were the electrolytes most frequently measured (averages of 14.1 and 13.1 per patient, respectively). More than 75% of the results were within normal range for all electrolytes measured and critical values were extremely uncommon. The number of phlebotomies for electrolyte measurements was strongly associated with the degree of hemoglobin drop (P < 0.0001). Electrolyte panels were ordered much more often than individual electrolytes with average cost exceeding $2200 per patient. Replacing half of these electrolyte panels with single sodium or potassium orders would have resulted in savings greater than $100,000 in our population. CONCLUSIONS: Electrolytes measurements are very frequent in the NICU, but results are most often normal and only exceptionally critical. The phlebotomies required for these tests significantly worsen hemoglobin levels. A more conservative use of electrolyte measurements can result in reduction of blood loss and substantial cost savings.

Neonatal screening for congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) caused by steroid 21-hydroxylase deficiency occurs in 1:16,000-1:20,000 births. If not promptly diagnosed and treated, CAH can cause death in early infancy from shock, hyponatremia and hyperkalemia. Affected girls usually have ambiguous genitalia but boys appear normal; therefore, newborn babies are commonly screened for CAH in the US and many other countries. By identifying babies with severe, salt-wasting CAH before they develop adrenal crises, screening reduces morbidity and mortality, particularly among affected boys. Diagnosis is based on elevated levels of 17-hydroxyprogesterone, the preferred substrate for steroid 21-hydroxylase. Initial testing usually involves dissociation-enhanced lanthanide fluorescence immunoassay that has a low positive predictive value (about 1%), which leads to many follow-up evaluations that have negative results. The positive predictive value might be improved by second-tier screening using DNA-based methods or liquid chromatography followed by tandem mass spectrometry, but these methods are not widely adopted. Cost estimates for such screening range from US$20,000 to $300,000 per life-year saved. In babies with markedly abnormal screen results, levels of serum electrolytes and 17-hydroxyprogesterone should be immediately determined, but the most reliable way to diagnose CAH is measurement of levels of steroid precursors after stimulation with cosyntropin.