Pre-dialysis levels of inflammation and endotoxin in people receiving hemodialysis are not associated with blood pressure variability.

There are multiple risk factors for inflammation in dialysis. One potential cause is the presence of circulating levels of Gram-negative bacteria-derived endotoxin which is a strong inducer of inflammation. Gut-associated endotoxin may enter the circulation via a defective blood-gut barrier during episodes of hypotension or reduced perfusion. MATERIALS AND METHODS: In this study, 165 patients receiving outpatient-based hemodialysis in a facility (FHD) or at home (HHD), were studied. Levels of inflammation were quantified by developing an inflammatory score derived from the measurement of pro-inflammatory cytokines, high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Intradialytic blood pressure (BP) variability and hypotension events were recorded. This included the final session of dialysis, at the commencement of which the blood samples were drawn, as well as the five preceding sessions. RESULTS: The median inflammatory score was 2 (range 0 - 3), and 30% of patients had an inflammatory score of three suggesting significant levels of inflammation. Only 8.5% had an inflammatory score of 0. Endotoxin was measured in all participants and was only positive in N = 3. The mean systolic blood pressure (SBP) was 134 ± 20 mmHg and the BP variability was 11.7 ± 3.5. In a multivariable ordinal regression model, a higher inflammatory score was significantly associated with younger age (OR 0.95, 95% CI 0.95 - 0.99, p = 0.03), higher ultrafiltration volume (OR 1.62, CI 1.04 - 2.54, p = 0.03) and lower body mass index (OR 0.9, CI 0.86 - 0.96, p = 0.01). There was no association between inflammatory score and dialysis modality, access type, kidney replacement therapy (KRT), BP variability, or endotoxin. Endotoxin was detected in only 3 of 165 patients and was not associated with inflammation. CONCLUSION: Pre-dialysis levels of inflammation are prevalent in the hemodialysis population after the long break but are not related to intradialytic BP variability or hypotension in the preceding 2 weeks. However, endotoxemia is uncommon and unlikely to be a significant driver of inflammation.

Copeptin is increased by nausea and vomiting during hypertonic saline infusion in healthy individuals.

OBJECTIVE: Measurement of hypertonic saline-stimulated copeptin has recently been described for the differentiation of polyuria-polydipsia syndrome. This study aims to determine the copeptin response to intravenous 3% hypertonic saline, including evaluation of adverse effects, in a local cohort of healthy adults >18 years in Australia. DESIGN: Prospective clinical study. METHODS: Twenty healthy volunteers (10 males and 10 females) were recruited. Participants underwent infusion of 3% hypertonic saline via a previously described standardized protocol, until the plasma sodium was ≥150 mmol/L, with measurement of plasma copeptin. RESULTS: Mean peak sodium was 152 mmol/L ± SD 1.4 with osmolality 315 mmol/kg ± SD 3.9. Median volume of hypertonic saline infused to reach target sodium ≥ 150 mmol/L was 1536 mL (IQR 1362, 1992). Mean rate of plasma sodium rise was 5.9 mmol/L/hour ± SD 1.5. Hypertonic saline-stimulated copeptin had non-parametrical distribution with median of 33.8 pmol/L (IQR 27.6, 63.6). Overall median symptom burden was 6/10 (range 3/10-9/10). Copeptin was significantly higher for those who experienced nausea and/or vomiting (n = 13) (median 39.0 pmol/L; IQR 32.5, 90), compared to those participants who did not experience either (median 20.0 pmol/L; IQR 13.0, 31.0) (P = 0.003). There were no serious adverse events. CONCLUSION: Hypertonic saline-stimulated copeptin measurements were similar in our population compared with previously reported reference intervals in healthy volunteers. There is a wide range of stimulated copeptin measurements in the healthy population. Nausea and vomiting are common adverse effects which enhance the copeptin response.

The Effect of High-Flow Nasal Oxygen on Carbon Dioxide Accumulation in Apneic or Spontaneously Breathing Adults During Airway Surgery: A Randomized-Controlled Trial.

BACKGROUND: High-flow nasal oxygen (HFNO) is an emerging technology that has generated interest in tubeless anesthesia for airway surgery. HFNO has been shown to maintain oxygenation and CO2 clearance in spontaneously breathing patients and is an effective approach to apneic oxygenation. Although it has been suggested that HFNO can enhance CO2 clearance during apnea, this has not been established. The true extent of CO2 accumulation and resulting acidosis using HFNO during prolonged tubeless anesthesia remains undefined. METHODS: In a single-center trial, we randomly assigned 20 adults undergoing microlaryngoscopy to apnea or spontaneous ventilation (SV) using HFNO during 30 minutes of tubeless anesthesia. Serial arterial blood gas analysis was performed during preoxygenation and general anesthesia. The primary outcome was the partial pressure of CO2 (Paco2) after 30 minutes of general anesthesia, with each group compared using a Student t test. RESULTS: Nineteen patients completed the study protocol (9 in the SV group and 10 in the apnea group). The mean (standard deviation [SD]) Paco2 was 89.0 mm Hg (16.5 mm Hg) in the apnea group and 55.2 mm Hg (7.2 mm Hg) in the SV group (difference in means, 33.8; 95% confidence interval [CI], 20.6-47.0) after 30 minutes of general anesthesia (P < .001). The average rate of Paco2 rise during 30 minutes of general anesthesia was 1.8 mm Hg/min (SD = 0.5 mm Hg/min) in the apnea group and 0.8 mm Hg/min (SD = 0.3 mm Hg/min) in the SV group. The mean (SD) pH was 7.11 (0.04) in the apnea group and 7.29 (0.06) in the SV group (P < .001) at 30 minutes. Five (55%) of the apneic patients had a pH <7.10, of which the lowest measurement was 7.057. No significant difference in partial pressure of arterial O2 (Pao2) was observed after 30 minutes of general anesthesia. CONCLUSIONS: CO2 accumulation during apnea was more than double that of SV after 30 minutes of tubeless anesthesia using HFNO. The use of robust measurement confirms that apnea with HFNO is limited by CO2 accumulation and the concomitant severe respiratory acidosis, in contrast to SV. This extends previous knowledge and has implications for the safe application of HFNO during prolonged procedures.

The relationship between early post-operative ACTH / cortisol following pituitary surgery and long-term glucocorticoid requirement - Do ultradian rhythms matter?

OBJECTIVE: To determine whether early (4-8h) post-operative ACTH after trans-sphenoidal surgery (TSS) predicts long-term hypothalamic-pituitary-adrenal (HPA) axis function and to investigate early morning day 1 ACTH/cortisol variability using rapid sampling. DESIGN: Prospective observational study. METHODS: Participants undergoing TSS were included; those treated with glucocorticoids pre-operatively received 100 mg intravenous hydrocortisone on anaesthetic induction. ACTH and cortisol were measured post-operatively at + 4h and + 8h after induction and on day 1 every 10 minutes between 0700h and 0900h. PRIMARY OUTCOME: glucocorticoid requirement at 6 months. RESULTS: Nineteen participants (10F, 9M): 6/19 (32%) were treated with replacement glucocorticoids pre-operatively; 4 had ceased by 6 weeks post-operatively. One patient developed new hypopituitarism post-operatively meaning 3/19 (16%) required glucocorticoids at 6 months. Post-operative + 4h ACTH < 14.3 pmol/L (65 ng/L) predicted secondary adrenal insufficiency (SAI) (sensitivity 100%, specificity 75%), whilst no participant with a post-operative + 4h ACTH ≥ 14.3 pmol/L (65 ng/L) required glucocorticoids at 6 months. Day 1 ACTH and cortisol showed a significant circadian fall between 0700h-0900h; ACTH 4.2 pmol/L (IQR 2.9-5.9) to 3.7 pmol/L (IQR 2.9-5.1) P = .006 and cortisol 549 nmol/L (IQR 337-618) to 439 nmol/L (IQR 315-606) P < .001, with clinically insignificant ultradian secretory pulses. CONCLUSIONS: No participant with a post-operative + 4h ACTH ≥ 14.3 pmol/L (65 ng/L) required glucocorticoids at 6 months; however, given only 3/19 participants had the primary outcome of interest, this must be confirmed in a larger cohort. The timing of a day 1 morning cortisol between 0700h and 0900h influences the accuracy of a single cut-off to diagnose SAI after pituitary surgery.

Methamphetamine intoxication and acute kidney injury: A prospective observational case series.

AIM: The effects of methamphetamine intoxication on the kidney are not well reported. We aimed to investigate acute kidney injury (AKI) associated with methamphetamine intoxication, in particular its severity, duration and association with rhabdomyolysis. METHODS: This is a prospective observational series of methamphetamine-intoxicated patients presenting to an Emergency Department. Patients self-reporting recent methamphetamine use, with a positive urine drug screen and an elevated creatinine, were eligible for the study. Urinary neutrophil gelatinase-associated lipocalin (NGAL) was measured, and serum creatinine, creatine kinase and cystatin C concentrations were performed on arrival and at several time points until discharge from hospital. Demographic and clinical data were obtained from the medical records. RESULTS: There were 634 presentations with methamphetamine intoxication over a 10-month period, with 73/595(12%) cases having an elevated serum creatinine concentration on arrival. Fifty presentations in 48 patients were included in the study. Most patients (85%) were male with a median age of 32 years. The median serum creatinine concentration on presentation was 125 µmol/L (IQR:113-135 µmol/L) with 45 (90%) presentations meeting diagnostic criteria for AKI. Concurrent rhabdomyolysis occurred in 22 (44%) presentations with a median CK of 2695 U/L (IQR:1598-5060 U/L). Cystatin C was elevated (> 0.98 mg/L) in 18 cases. An elevated NGAL concentration (>150 µg/L) was present in five (10%) cases. No patients required dialysis. The median length of stay was 19 hours (IQR 14-24 hours). CONCLUSION: AKI is common in methamphetamine intoxication. The kidney injury is relatively mild and short-lived, resolving with crystalloid therapy.

Elevated insulin-like growth factor-1 in Cushing's disease.

OBJECTIVE: To determine if patients with untreated Cushing's disease have higher serum insulin-like growth factor-1 (IGF-1) compared to matched controls, and if IGF-1 decreases following remission of Cushing's disease. DESIGN: Retrospective case-control study matching Cushing's disease cases to control patients for adenoma size, age, sex, diabetic and gonadal status, body mass index and serum IGF-1 measured within one year. Paired analysis of pre-operative (untreated) and >3 months post-operative (remission) serum IGF-1 for cases. PATIENTS AND MEASUREMENTS: All patients were investigated at the Princess Alexandra Hospital Endocrine Unit between 2005 and 2017. Serum IGF-1 was measured in 25 cases and 49 controls, 23 case-control pairs and 13 cases pre- and post-operatively. RESULTS: Mean serum IGF-1 in cases was significantly higher compared to controls-32 ± 12 nmol/L compared to 25 ± 8 nmol/L, (P = 0.005). The proportion of cases with elevated serum IGF-1 above an age-adjusted reference range was higher compared to 1:1 matched controls (8/23 (35%) vs 1/23 (4%), P = 0.02). In 13 cases in remission post-operatively, serum IGF-1 decreased significantly from 31 (IQR 29-40.5) nmol/L to 23 (IQR 15-28.5) nmol/L, (P < 0.001), despite no difference in the prevalence of pre- vs post-operative pituitary hormone dysfunction (P = 0.47). CONCLUSION: Patients with untreated Cushing's disease may have elevated IGF-1, which decreases following remission. Mildly elevated IGF-1 in Cushing's disease does not imply pathological growth hormone (GH) excess.

Chronic kidney cortical damage is associated with baseline kidney function and albuminuria in patients managed with radical nephrectomy for kidney tumours.

This study evaluated the relationship between histological markers of chronic kidney damage in patients undergoing radical nephrectomy for kidney tumours and preoperative kidney function, degree of albuminuria, and changes in glomerular volume. A schema to grade chronic kidney damage could be used to identify patients at risk of developing CKD following nephrectomy. Non-neoplastic cortical tissue was sourced from 150 patients undergoing radical nephrectomy for suspected kidney cancer. This tissue was evaluated for indicators of chronic damage, specifically: glomerulosclerosis, arteriosclerosis, interstitial fibrosis, and tubular atrophy. Glomerular volume was determined using the Weibel and Gomez method. Associations between these parameters and both estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) were determined using either a Mann-Whitney U-test or a Kruskal-Wallis ANOVA. Associations between both eGFR and ACR and glomerular volume were assessed using linear regression. eGFR was inversely associated with the degree of glomerulosclerosis (p < 0.001), vascular narrowing (p = 0.002), tubular atrophy (p < 0.001), and interstitial fibrosis (p < 0.001). ACR was associated only with the degree of interstitial fibrosis (p = 0.02) and tubular atrophy (p = 0.02). Glomerular volume was greater for males, diabetics, hypertensive patients, and patients with a greater degree of interstitial fibrosis. Glomerular volume was positively associated with ACR. A schema to grade chronic damage was developed. The proposed schema is associated with baseline clinical indices of kidney function and damage. Longitudinal validation is necessary to determine the prognostic utility of this schema.

Acute bone marrow suppression and gastrointestinal toxicity following acute oral methotrexate overdose.

OBJECTIVE: Acute methotrexate overdose rarely causes systemic toxicity due to saturable absorption and rapid renal elimination. We present a case of methotrexate toxicity following acute overdose. CASE REPORT: A 56-year-old female presented soon after an overdose of 1250 mg of methotrexate, zopiclone and tramadol. The methotrexate was initially under-reported (500 mg) and folinic acid was not provided. Despite normal renal function, the patient developed toxicity. She represented 5 days following the overdose with mucositis, bone marrow suppression and prolonged febrile neutropenia. Treatment included folinic acid, broad-spectrum antibiotics, filgrastim, red cell and platelet transfusion. Her bone marrow began to recover 12 days following the overdose. She was discharged home on Day 17. DISCUSSION: Severe toxicity following an acute ingestion of a large amount of methotrexate is rarely reported. The development of toxicity was unexpected in this case given methotrexate's pharmacokinetics and the patient's normal renal function. The serum methotrexate concentrations were below the treatment threshold of the folinic acid rescue therapy nomogram suggesting that the nomogram should not be relied on in acute ingestions. Large acute oral methotrexate poisoning can result in systemic toxicity and folinic acid therapy should be provided in ingestions >1000 mg.

Factors associated with acutely elevated serum creatinine following radical tumour nephrectomy: the Correlates of Kidney Dysfunction-Tumour Nephrectomy Database study.

BACKGROUND: To identify factors associated with acutely elevated serum creatinine (SCr) within 7 days of radical tumour nephrectomy. METHODS: The study population consisted of 130 consecutive patients managed for renal tumours. The primary outcome was acute kidney injury (AKI) (defined as SCr increase ≥50% above baseline), assessed using multivariable logistic regression analysis. The secondary outcome was SCr percentage increase, assessed using multivariable linear regression analysis. RESULTS: Following nephrectomy, the mean percentage increase in SCr in the first week was 55%±29%, and 77 (59%) patients experienced AKI. Independent predictors of AKI post-nephrectomy were male gender [adjusted odds ratio (OR): 2.67; 95% confidence interval (95% CI): 1.01, 6.93], urine albumin-creatinine ratio (OR: 0.66; 95% CI: 0.47, 0.91), preoperative estimated glomerular filtration rate (eGFR) (OR: 1.03; 95% CI: 1.00, 1.05), laparoscopic nephrectomy (OR: 3.02; 95% CI: 1.00, 9.12), and non-clear cell renal cell carcinoma (RCC) (OR: 2.93; 95% CI: 1.04, 8.29). Independent predictors of a SCr increase were male gender (ß: 12.0; 95% CI: 2.69, 21.3), urine albumin-creatinine ratio (ß: -3.36; 95% CI: -6.55, -0.16), preoperative eGFR (ß: 0.38; 95% CI: 0.10, 0.66), laparoscopic nephrectomy (ß: 12.7; 95% CI: 1.05, 24.3) and obesity (ß: 9.94, 95% CI: 0.61, 19.3). CONCLUSIONS: Male gender, albuminuria, eGFR and laparoscopic nephrectomy independently associated with acutely elevated serum creatinine following radical tumour nephrectomy.

Prospective evaluation of a week one overnight metyrapone test with subsequent dynamic assessments of hypothalamic-pituitary-adrenal axis function after pituitary surgery.

OBJECTIVE: To determine whether an overnight metyrapone test (OMT) within the first week postpituitary surgery can definitively assess the hypothalamic-pituitary-adrenal (HPA) axis, compared with subsequent dynamic tests and glucocorticoid requirement at 6 months. DESIGN: Prospective study measuring morning cortisol levels on days 3 and 4 post-operatively, OMT day 5-7 and week 6, week 6 250 µg short Synacthen test (SST) and week 7 insulin tolerance test (ITT). PATIENTS AND MEASUREMENTS: Forty participants who underwent pituitary surgery at a single centre (Cushing's disease excluded) were followed for at least 6 months. 46% had pre-operative adrenal insufficiency. PRIMARY OUTCOME: week 1 OMT compared to glucocorticoid requirement at 6 months. SECONDARY OUTCOMES: the performance of ITT as a "definitive" test and all tests compared to glucocorticoid requirement at 6 months. RESULTS: Week 1 OMT showed concordance with ITT at week 7 of 78% and glucocorticoid requirement at 6 months of 81% respectively which was not significantly different from post-operative morning cortisol levels; 37% of participants with an abnormal OMT on day 6 had a normal OMT at week 6. All HPA axis tests showed similar concordance with glucocorticoid requirement at 6 months of 80%-85%. CONCLUSIONS: Overnight metyrapone test within the first week after pituitary surgery was no better than an early morning cortisol level at predicting glucocorticoid requirement at 6 months. OMT at week 6 demonstrated recovery of HPA axis in a substantial proportion of participants who failed earlier assessments; thus, definitive testing should be delayed until 6 weeks post-operatively.

The need to address poor numeracy skills in the emergency department environment.

Substantial evidence exists for lack of numerical skills among many health professionals. Although poor numeracy has long been recognised as a contributor to medication error, other activities for which numerical literacy are required, such as interpretation of diagnostic results, have been largely ignored. Poor self-awareness of lack of numerical literacy increases the risk, especially in the busy and hurried emergency environment. System changes, such as standardising units and improving number presentation, reduce the potential for misinterpretation; however system changes do not address the underlying deficiencies in mathematical skills. The training of doctors in numeracy has been largely ignored. In contrast, education for nurses frequently occurs during both pre- and post-registration programmes. Interventions have had mixed success, although additional emphasis in increasing conceptual understanding of numbers is encouraging. The consequences of poor numerical literacy should be addressed in all clinical staff, not only by practice change to remove the potential for errors to be made, but also complemented by self-awareness and education.

Profiling of immunoglobulins in resting and mechanically stimulated saliva.

BACKGROUND: Dysregulation of salivary immunoglobulins has been implicated in illnesses ranging from periodontal disease to HIV aids and malignant cancers. Despite these advances there is a lack of agreement among studies with regard to the salivary immunoglobulin levels in healthy controls. METHODOLOGY: Resting and mechanically stimulated saliva samples and matching serum samples were collected from healthy individuals (n = 33; 40-55 years of age; gender: 23 female, 10 male). A matrix-matched AlphaLISA(®) assay was developed to determine the concentrations of IgG1 and IgG4 in serum and saliva samples. CONCLUSION: Clear relationships were observed in the flow rate and concentration of each immunoglobulin in the two types of saliva. This study affirms the need to establish and standardize collection methods before salivary IgGs are used for diagnostic purposes.

Uremic toxin development in living kidney donors: a longitudinal study.

BACKGROUND: Emerging evidence suggests that uremic toxins, in particular indoxyl sulfate (IS) and p-cresyl sulfate (PCS), may be involved in the pathogenesis of cardiovascular disease. Despite a significant increase in IS and PCS in patients with established kidney damage, the effect of a nephrectomy in non-chronic kidney disease patients is not yet known. METHODS: Forty-two living kidney donors (Caucasian; 76% female [n=32]; 53 ± 10 years) were enrolled in an observational cohort study and followed up annually for 2 years (before nephrectomy, 1 and 2 years after nephrectomy). At each time point, patients underwent measurements of serum total and free IS and PCS (using ultrahigh-performance liquid chromatography), carotid intima-media thickness (a measure of arterial stiffness), brachial artery reactivity (both flow-mediated dilatation and sublingual glycerol trinitrate, markers of endothelial dysfunction), kidney function by Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C, and urate and high-sensitivity C-reactive protein using standard laboratory techniques. RESULTS: Kidney function decreased by 30% after nephrectomy (absolute change estimated glomerular filtration rate 28 ± 6.9 and 27 ± 7.6 mL/min/1.73 m at 1 and 2 years, respectively), and the concentration of toxin levels increased by 44% to 100%, which remained elevated at 2 years after nephrectomy (all P<0.001). Both toxins were associated with carotid intima-media thickness, brachial artery reactivity-glycerol trinitrate, serum urate, and C-reactive protein levels (all P<0.03). Further, IS and urate were found to be independent predictors of change in kidney function, from baseline at 2 years after nephrectomy (both P<0.03). CONCLUSION: This study demonstrated significant and sustained increases in nephrovascular toxins, IS and PCS, after nephrectomy. Levels of both toxins were associated with clinically relevant markers of cardiovascular and renal risk, warranting further research in this area.

Target concentration intervention in oncology: where are we at?

Therapeutic drug monitoring (TDM) and more recently target concentration intervention (TCI) have been widely used in clinical practice for the optimization of drug treatment. TDM and TCI have been applied most frequently in the cardiovascular, respiratory, neurology, and infectious disease areas because the medications used here have both narrow therapeutic indices and a clear relationship between concentration and effect. However, apart from drugs such as methotrexate and 5-fluorouracil, the clinical application of TDM/TCI in oncology is minimal. An important reason for this is that a therapeutic index for most anticancer agents has not been established. However, in the last 20 years, relationships between plasma drug concentrations and clinical outcome have been defined for various chemotherapeutic agents. Defining concentration-effect relationships is also complicated by the fact that cancer is almost always treated with multiple drugs given in combination making the precise definition of the pharmacodynamics of individual agents difficult. The increase in patients with obesity and also those underweight adds to the complexity of effective oncology treatment. This review describes some of the evidence that supports the use of TDM/TCI in oncology. It is proposed that as more patients previously ineligible for chemotherapy become eligible, TDM/TCI may play a critical role in optimizing chemotherapy outcomes. However, pharmacokinetic-pharmacodynamic research to investigate both therapeutic benefit and feasibility in daily clinical practice is required.

One-step homogeneous C-reactive protein assay for saliva.

BACKGROUND: Cardiovascular disease is the leading cause of death in the world. Human C-reactive protein (CRP) has been used in the risk assessment of coronary events. Human saliva mirrors the body's health and well-being and is non-invasive, easy to collect and ideal for third world countries as well as for large patient screening. The aim was to establish a saliva CRP reference range and to demonstrate the clinical utility of salivary CRP levels in assessing the coronary events in a primary health care setting. METHODS: We have used a homogeneous bead based assay to detect CRP levels in human saliva. We have developed a rapid 15 min (vs 90 min), sequential, one-step assay to detect CRP in saliva. Saliva was collected from healthy volunteers (n=55, ages 20-70 years) as well as from cardiac patients (n=28, ages 43-86 years). RESULTS: The assay incubation time was optimised from 90 min to 15 min and generated a positive correlation (n=29, range 10-2189 pg/mL, r2=0.94; Passing Bablok slope 0.885, Intercept 0, p>0.10), meaning we could decrease the incubation time and produce equivalent results with confidence. The mean CRP level in the saliva of healthy human volunteers was 285 pg/mL and in cardiac patients was 1680 pg/mL (p<0.01). Analysis of CRP concentrations in paired serum and saliva samples from cardiac patients gave a positive correlation (r2=0.84, p<0.001) and the salivary CRP concentration capable of distinguishing healthy from diseased patients. CONCLUSIONS: The results suggest that this minimally invasive, rapid and sensitive assay will be useful in large patient screening studies for risk assessment of coronary events.

Evaluation of the Becton-Dickinson rapid serum tube: does it provide a suitable alternative to lithium heparin plasma tubes?

BACKGROUND: Obtaining a suitable specimen for analysis in a timely manner is pivotal in clinical chemistry service provision. Serum is recognized as the preferred specimen for most assays, but because of time constraints for completion of clotting and an increasing number of patients on anti-coagulant therapy, latent clotting or no clotting is an outcome which can lead to errors and delay in delivery of critical results. Although lithium heparin plasma has unique problems, it has become an alternative in hospital-based laboratories. METHODS: The Becton-Dickinson (BD) rapid serum tube (RST) was evaluated in a hospital environment using a total of 53 participants, both healthy and anticoagulated, for 31 analytes against BD PST II and BD SST II tubes measured with Beckman DxC800 and DxI800 analyzers. RESULTS: Most results from the RST tube were comparable with those from the SST II tube. Potassium results were closer to the PST II plasma concentrations. Incomplete and latent clotting was encountered in the RST specimens from participants (cardiac and dialysis) who had received a total of >7000 units of heparin [activated partial thromboplastin time (APTT) >150 s], warfarin/heparin combination, and specimens from cardiac surgery patients who had received a total of >25,000 units of heparin (APTT >200 s) at the time of collection of specimens. CONCLUSIONS: The RST tube provides a suitable alternative to lithium heparin plasma tubes for most patients in a hospital environment. However, latent clotting continued to occur in specimens collected from participants who had received high concentrations of anticoagulants.

Plasma protein C levels in immunocompromised septic patients are significantly lower than immunocompetent septic patients: a prospective cohort study.

INTRODUCTION: Activated Protein C [APC] improves outcome in immunocompetent patients with severe sepsis particularly in those who are perceived to have high mortality risk. Before embarking on a trial of APC administration in immunocompromised septic patients, a preliminary study on plasma levels of protein C in this cohort is essential. OBJECTIVE: To assess serum Protein C concentrations in immunocompromised patients as compared to immunocompetent patients during sepsis, severe sepsis, septic shock and recovery. METHODS: Prospective cohort study in a tertiary hospital. Patients satisfying inclusion criteria were enrolled after informed consent. Clinical variables were noted with sample collection when patients met criteria for sepsis, severe sepsis, septic shock and recovery. Protein C levels were measured using monoclonal antibody based fluorescence immunoassay. RESULTS: Thirty one patients participated in this study (22 immunocompromised, 9 immunocompetent). Protein C levels were found to be significantly lower in the immunocompromised group compared to the immunocompetent group, particularly observed in severe sepsis [2.27 (95% CI: 1.63-2.9) vs 4.19 (95% CI: 2.87-5.52) mcg/ml] (p = 0.01) and sepsis [2.59 (95% CI: 1.98-3.21) vs 3.64 (95% CI: 2.83-4.45) mcg/ml] (p = 0.03). SOFA scores were similar in both the groups across sepsis, severe sepsis and septic shock categories. Protein C levels improved significantly in recovery (p = 0.001) irrespective of immune status. CONCLUSION: Protein C levels were significantly lower in immunocompromised patients when compared to immunocompetent patients in severe sepsis and sepsis categories. Our study suggests a plausible role for APC in severely septic immunocompromised patients which need further elucidation.