Effect of Uric Acid Control on Serum Creatinine.

OBJECTIVE: Hyperuricemia has been epidemiologically associated with multiple comorbidities including chronic renal failure and cardiovascular disease. Cause and effect are difficult to address, given comorbidities associated with and prevalence of metabolic syndrome. One impediment to achieving serum uric acid (sUa) levels less than or equal to 6.0 mg/DL is the concept that allopurinol might be nephrotoxic. We examined the relation of sUa less than or equal to 6.0 mg/dL to renal function over time. METHODS: This is a medical records review study of 348 hyperuricemia patients identified in 2015, as having been followed with serial uric acid measurements. After 1 year of serial urate levels, to allow for treatment, patient cohorts were defined: sUa less than or equal to 6.0 mg/dL and sUa greater than 6.0 mg/dL. A repeated measure model was used to test for an association between uric acid level and serum creatinine, while adjusting for covariates. RESULTS: There was a significant difference in the least square means of serum creatinine comparing those who achieved an sUa less than or equal to 6.0 mg/dL versus sUa greater than 6.0 mg/dL (1.39 mg/dL [95% confidence interval, 1.30-1.48] vs 1.57 mg/dL [95% confidence interval, 1.46-1.69]; p = 0.0015). This is a between-group difference in creatinine of 0.18 mg/dL. If a change in serum creatinine of 0.2 is considered significant, this short-term between-group progression of renal failure approaches clinical significance. CONCLUSIONS: Given that most serial measures were within the first few years of follow-up, and change in renal function occurs slowly over time, the between group difference of sUa of 0.18 mg/dL is close to a clinically significant creatinine difference of 0.2 mg/dL.

Reproducibility of point-of-care ultrasonography for central vein diameter measurement: Separating image acquisition from interpretation.

PURPOSE: Central vein point-of-care ultrasonography must be reproducible to detect intravascular volume changes. We sought to determine which measurement step, image acquisition or interpretation, could be more compromising for reproducibility. METHODS: Three investigators each acquired inferior vena cava (IVC) and internal jugular (IJV) vein ultrasonographic sequences (US) from a convenience sample of 21 hospitalized general medicine participants and then interpreted each US three separate times. We partitioned the random errors of acquisition and interpretation, attributing wider dispersions of each to larger reductions in reproducibility. RESULTS: We analyzed 351 interpretations of 39 IVC and 432 interpretations of 48 IJV US. Reproducibility of the maximum (standard error of measurement 3.3 mm [95% confidence interval, CI 2.7-4.2 mm]) and minimum (4.8 mm [3.9-6.3 mm]) IVC diameter measurements were worse than that of the mediolateral (2.5 mm [2.0-3.2 mm]) and anteroposterior (2.5 mm [2.0-3.1 mm]) IJV diameters. The dispersions of random measurement errors were wider among acquisitions than interpretations. CONCLUSIONS: Among our investigators, central vein diameter measurements obtained by point-of-care ultrasonography are not sufficiently reproducible to distinguish clinically meaningful intravascular volume changes from measurement errors. Reproducibility could be most effectively improved by reducing the random measurement errors of acquisition. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:488-496, 2017.

Variable pharmacokinetics of extended interval tobramycin or gentamicin among critically ill patients undergoing continuous venovenous hemofiltration.

BACKGROUND/AIMS: Aminoglycosides are a major weapon against serious Gram-negative rod infections, yet aminoglycoside usage is limited by the risk of nephrotoxicity. The risk of toxicity is reduced by extended-interval dosing of aminoglycosides, defined as 5 - 7 mg/kg given intravenously in intervals of 24 hours or greater based on serum drug concentrations. In critically ill patients undergoing continuous venovenous hemofiltration, there are few published reports of the pharmacokinetics of extended-interval dosing of aminoglycosides. METHODS: We evaluated the pharmacokinetics of extended-interval dosing of gentamicin and tobramycin in 9 critically ill patients on continuous venovenous hemofiltration at Dartmouth-Hitchcock Medical Center between April 2007 and September 2011. RESULTS: Aminoglycoside elimination half-life values were highly variable (median 7 hours, range 3 - 26 hours) and did not correlate with total body weight or estimated creatinine clearance derived from the dose of continuous venovenous hemofiltration. Five of 9 patients cleared infection, but only 4 patients survived to hospital discharge, 2 of whom were dialysis-dependent. CONCLUSION: Extended interval aminoglycoside dosing during continuous venovenous hemofiltration yields unpredictable half-lives and drug levels among high-risk critically ill patients. Close monitoring of serum aminoglycoside levels is required.

Unusual neurological syndrome induced by atmospheric pressure change.

BACKGROUND: We describe a case of a 46-yr-old female who developed hypertension, tachycardia, dysarthria, and leg weakness provoked by pressure changes associated with flying. Typically during the landing phase of flight, she would feel dizzy and note that she had difficulty with speech and leg weakness. After the flight the leg weakness persisted for several days. The symptoms were mitigated when she took a combined alpha-beta blocker (labetalol) prior to the flight. CASE STUDY: To determine if these symptoms were related to atmospheric pressure change, she was referred for testing in a hyperbaric chamber. She was exposed to elevated atmospheric pressure (maximum 1.2 ATA) while her heart rate and blood pressure were monitored. Within 1 min she developed tachycardia and hypertension. She also quickly developed slurred speech, left arm and leg weakness, and sensory changes in her left leg. She was returned to sea level pressure and her symptoms gradually improved. A full neurological workup has revealed no explanation for these findings. She has no air collections, cysts, or other anatomic findings that could be sensitive to atmospheric pressure change. DISCUSSION: The pattern is most consistent with a vascular event stimulated by altitude exposure. This case suggests that atmospheric pressure change can produce neurological symptoms, although the mechanism is unknown.

Dysnatremia in the ICU.

PURPOSE OF REVIEW: Dysnatremias, disorders of sodium concentration, are exceedingly common in critically ill patients and confer increased risk for adverse outcomes including mortality. The physiology that underpins the diagnosis and management of these disorders is complex. This review seeks to discuss current literature regarding the pathophysiology, diagnosis, epidemiology, and management of these disorders. RECENT FINDINGS: The role of arginine vasopressin in the maintenance of normal and pathologic plasma osmolality increasingly is refined, improving our ability to diagnose and understand dysnatremia. Identified recent epidemiologic studies highlight the frequent hospital acquisition or exacerbation of dysnatremia, confirm the recognized adverse consequences and explore the potential causality. Despite the complex nature of these disorders, simple consensus treatment strategies have emerged. SUMMARY: Dysnatremia remains a common disorder across the spectrum of critically ill patients. It is frequently hospital acquired. Simplified treatment regimens are proposed and the potential for prevention or earlier recognition and intervention is emphasized. Future directions of interest include further exploration of how dysnatremia contributes to adverse outcomes and new treatment strategies.

Life-threatening hyperkalemia from nutritional supplements: uncommon or undiagnosed?

Potassium chloride and other potassium compounds are used by the general public as salt substitutes, muscle-building supplements, and panacea. Severe hyperkalemia from oral potassium is extremely rare if kidney function is normal because of potassium adaptation. The oral potassium dose has to be large enough to overcome the normal renal excretory mechanisms to cause severe hyperkalemia. This occurs most commonly in patients with renal impairment or those who take potassium-sparing diuretics, angiotensin receptor blockers, or angiotensin-converting enzyme inhibitors. We present two unique cases of near-fatal hyperkalemia from nutritional supplements containing potassium. The first case was due to salt-substitute intake, whereas the second case was from a muscle-building supplement. Both patients suffered cardiac arrest, but were successfully resuscitated and survived. The acuity of intake and excessive quantity overwhelmed the kidneys' ability for adaptation. Potassium toxicity affects multiple organ systems and manifests in characteristic, acute cardiovascular changes with electrocardiographic abnormalities. Neuromuscular manifestations include general muscular weakness and ascending paralysis may occur, whereas gastrointestinal symptoms manifest as nausea, vomiting, paralytic ileus, and local mucosal necrosis that may lead to perforation. Once an urgent situation has been handled with intravenous push of a 10% calcium salt, short-term measures should be started with agents that cause a transcellular shift of potassium, namely, insulin with glucose, ß2-agonist, and NaHCO(3). Patients are unaware of these potentially serious adverse effects, and there are inadequate consumer warnings. Clinicians should be vigilant in monitoring potassium intake from over-the-counter supplements.

Peritoneal dialysis masking symptoms of an insulinoma uncovered during the perioperative period: a case report.

A 61-year-old male with a chronic history of renal insufficiency treated with peritoneal dialysis (PD) was discovered to be asymptomatic for an occult insulinoma after peripheral revascularization. The patient's near continuous provision of glucose in the PD fluid acted to conceal symptoms of an insulinoma which was revealed when PD was interrupted. The patient had delayed emergence from general anesthesia resolving with glucose administration, precipitating insulinoma work up.

Clinical measurements obtained from point-of-care ultrasound images to assess acquisition skills.

BACKGROUND: Current methods of assessing competence in acquiring point-of-care ultrasound images are inadequate. They rely upon cumbersome rating systems that do not depend on the actual outcome measured and lack evidence of validity. We describe a new method that uses a rigorous statistical model to assess performance of individual trainees based on the actual task, image acquisition. Measurements obtained from the images acquired (the actual desired outcome) are themselves used to validate effective training and competence acquiring ultrasound images. We enrolled a convenience sample of 21 spontaneously breathing adults from a general medicine ward. In random order, two trainees (A and B) and an instructor contemporaneously acquired point-of-care ultrasound images of the inferior vena cava and the right internal jugular vein from the same patients. Blinded diameter measurements from each ultrasound were analyzed quantitatively using a multilevel model. Consistent mean differences between each trainee's and the instructor's images were ascribed to systematic acquisition errors, indicative of poor measurement technique and a need for further training. Wider variances were attributed to sporadic errors, indicative of inconsistent application of measurement technique across patients. In addition, the instructor recorded qualitative observations of each trainee's performance during image acquisition. RESULTS: For all four diameters, the means and variances of measurements from trainee A's images differed significantly from the instructor's, whereas those from trainee B's images were comparable. Techniques directly observed by the instructor supported these model-derived findings. For example, mean anteroposterior diameters of the internal jugular vein obtained from trainee A's images were 3.8 mm (90% CI 2.3-5.4) smaller than from the instructor's; this model-derived finding matched the instructor's observation that trainee A compressed the vein during acquisition. Instructor summative assessments agreed with model-derived findings, providing internal validation of the descriptive and quantitative assessments of competence acquiring ultrasound images. CONCLUSIONS: Clinical measurements obtained from point-of-care ultrasound images acquired contemporaneously by trainees and an instructor can be used to quantitatively assess the image acquisition competence of specific trainees. This method may obviate resource-intensive qualitative rating systems that are based on ultrasound image quality and direct observation, while also helping instructors guide remediation.

Limited agreement between two noninvasive measurements of blood volume during fluid removal: ultrasound of inferior vena cava and finger-clip spectrophotometry of hemoglobin concentration.

OBJECTIVE: Plots of blood volume measurements over time (profiles) may identify euvolemia during fluid removal for acute heart failure. We assessed agreement between two noninvasive measurements of blood volume profiles during mechanical fluid removal, which exemplifies the interstitial fluid shifts that occur during diuretic-induced fluid removal. APPROACH: During hemodialysis we compared change in maximum diameter of the inferior vena cava by ultrasound ([Formula: see text]) to change in relative blood volume derived from capillary hemoglobin concentration from finger-clip spectrophotometry (RBVSpHb). We grouped profiles of these measurements into three distinct shapes using an unbiased, data-driven modeling technique. METHODS: Fifty patients who were not in acute heart failure underwent a mean of five paired measurements while an average of 1.3 liters of fluid was removed over 2 h during single hemodialysis sessions. [Formula: see text] changed -1.0 mm (95% CI -1.9 to -0.2 mm) and the RBVSpHb changed -1.1% (95% CI -2.7 to +0.5%), but these changes were not correlated (r -0.04, 95% CI -0.32 to +0.24). Nor was there agreement between categorization of profiles of change in the two measurements (kappa -0.1, 95% CI -0.3 to +0.1). SIGNIFICANCE: [Formula: see text] and RBVSpHb estimates of blood volume do not agree during mechanical fluid removal, likely because regional changes in blood flow and pressure modify IVC dimensions as well as changes total blood volume.

Mucormycosis peritonitis: more than 2 years of disease-free follow-up after posaconazole salvage therapy after failure of liposomal amphotericin B.

A 57-year-old woman with end-stage kidney disease secondary to autosomal dominant polycystic kidney disease developed peritoneal dialysis-related Mucor peritonitis after her pet cockatoo bit through her transfer set. The infection persisted despite more than 8 weeks of treatment with liposomal amphotericin B. On a compassionate basis, she then received oral posaconazole, 800 mg/d, in divided doses for 6 months. She experienced complete remission and has remained disease free since then, for more than 2 years. We review the medical literature about mucormycosis peritonitis which, albeit rare, carries very high mortality. The treatment of choice is liposomal amphotericin B, which failed in our patient. Our case report suggests that posaconazole is an attractive treatment option in patients with peritoneal dialysis-related Mucor peritonitis.

A Review of the Use of Iloprost, A Synthetic Prostacyclin, in the Prevention of Radiocontrast Nephropathy in Patients Undergoing Coronary Angiography and Intervention.

Iloprost, a prostacyclin analogue, has been effective in preventing renal dysfunction among transplant patients. We hypothesized that iloprost is protective against renal dysfunction in different settings, in which similar underlying mechanisms of nephrotoxicity occur. We conducted a literature review, and discuss the application of iloprost in reducing acute renal insufficiency and the pathophysiological mechanisms of contrast-induced nephropathy (CIN). One proposed mechanism of CIN is prolonged renal arterial vasoconstriction, causing renal hypoperfusion, ischemia, and release of free radicals. Iloprost is an analogue of the vasodilatory prostaglandin PGI2 . It has demonstrated cytoprotective properties in the renal transplant population by inhibiting lysosomal degradation and release of free radicals, allowing membrane stabilization. Two good-quality studies reported on iloprost and CIN. Five studies reported protective effects of iloprost in renal transplantation and 1 in coronary artery bypass grafting. Iloprost was found to be renoprotective in patients with baseline renal insufficiency who underwent coronary angiography for CIN (risk ratio [RR] = 0.32, 95% confidence interval [CI]: 0.16-0.67) and increases the weighted mean difference improvement in creatinine clearance (RR = 4.56, 95% CI: 1.82-7.30). CIN is associated with major adverse cardiac events. Preventing CIN is important for patient safety and reducing disease burden. Iloprost may reduce CIN by up to 68%. The same mechanisms of iloprost that inhibit graft dysfunction in the acute post-renal transplant and cardiopulmonary bypass setting may also contribute to preventing CIN. Large randomized controlled trials are necessary to determine the clinical efficacy of iloprost in the angiography setting.

Meta-analysis of the effect of automated contrast injection devices versus manual injection and contrast volume on risk of contrast-induced nephropathy.

Contrast-sparing devices have been slowly adopted into routine patient care. Randomized trial evidence of automated contrast injectors (ACIs) has not been analyzed to evaluate the true reduction in contrast volume during coronary angiography and intervention. It has been thought that reducing the amount of contrast exposure will result in a simultaneous reduction in the risk of contrast-induced nephropathy (CIN). Therefore, we sought to synthesize published evidence on contrast-sparing devices, contrast volume, and the incidence of CIN. We searched Medline, the Cochrane Library, and Clinicaltrials.gov. The search criteria included ACIs versus manual injection, contrast media volume, and the incidence of CIN. Data were extracted by 2 independent reviewers. The weighted mean difference of contrast volume was calculated using random effects models in RevMan, version 5.4.1, software to derive a summary estimate. A total of 79,694 patients from 10 studies were included (ACI arm, n = 20,099; manual injection arm, n = 59,595). On average, ACIs reduced contrast volume delivery by 45 ml/case (p <0.001, 95% confidence interval -54 to -35). The CIN incidence was significantly reduced by 15%, with an odds ratio of 0.85 (p <0.001, 95% confidence interval 0.78 to 0.93) for those using ACIs compared with manual injection. In conclusion, the use of ACIs in angiography significantly reduces the volume of contrast delivered to the patient and the incidence of CIN.

Does safe dosing of iodinated contrast prevent contrast-induced acute kidney injury?

BACKGROUND: Previous work on contrast-induced acute kidney injury (CI-AKI) has identified contrast volume as a risk factor and suggested that there is a maximum allowable contrast dose (MACD) above which the risk of CI-AKI is markedly increased. We hypothesized that there is a relationship between contrast volume and CI-AKI and that there might be reason to track incremental contrast volumes above and below the MACD limit. METHODS AND RESULTS: Consecutive patients undergoing percutaneous coronary intervention (PCI) were prospectively enrolled from 2000 to 2008 (n=10 065). Patients on dialysis before PCI were excluded (n=155). MACD was defined as (5 mL x body weight [kg])/baseline serum creatinine [mg/dL]) and divided into categories in which 1.0 reflects the MACD limit: < or =MACD ratios (<0.5, 0.5 to 0.75, and 0.75 to 1.0) and >MACD (1.0 to 1.5, 1.5 to 2.0, and >2.0). CI-AKI was defined as a > or =0.3 (mg/dL) or > or =50% increase in serum creatinine from baseline or new dialysis. Multivariable regression was conducted to evaluate the effect of exceeding the MACD on CI-AKI. Twenty percent of patients exceeded the MACD. Risk-adjusted CI-AKI increased by an average of 45% for each category exceeding the MACD (odds ratio, 1.45; 95% confidence interval, 1.29 to 1.62) Adjusted odds ratios for each category exceeding the MACD were 1.60 (95% confidence interval, 1.29 to 1.97), 2.02 (95% confidence interval, 1.45 to 2.81), and 2.94 (95% confidence interval, 1.93 to 4.48). CI-AKI for contrast dose

Sodium bicarbonate plus N-acetylcysteine prophylaxis: a meta-analysis.

OBJECTIVES: We sought to conduct a meta-analysis to compare N-acetylcysteine (NAC) in combination with sodium bicarbonate (NaHCO(3)) for the prevention of contrast-induced acute kidney injury (AKI). BACKGROUND: Contrast-induced AKI is a serious consequence of cardiac catheterizations and percutaneous coronary interventions (PCI). Despite recent supporting evidence for combination therapy, not enough has been done to prevent the occurrence of contrast-induced AKI prophylactically. METHODS: Published randomized controlled trial data were collected from OVID/PubMed, Web of Science, and conference abstracts. The outcome of interest was contrast-induced AKI, defined as a >or=25% or >or=0.5 mg/dl increase in serum creatinine from baseline. Secondary outcome was renal failure requiring dialysis. RESULTS: Ten randomized controlled trials met our criteria. Combination treatment of NAC with intravenous NaHCO(3) reduced contrast-induced AKI by 35% (relative risk: 0.65; 95% confidence interval: 0.40 to 1.05). However, the combination of N-acetylcysteine plus NaHCO(3) did not significantly reduce renal failure requiring dialysis (relative risk: 0.47; 95% confidence interval: 0.16 to 1.41). CONCLUSIONS: Combination prophylaxis with NAC and NaHCO(3) substantially reduced the occurrence of contrast-induced AKI overall but not dialysis-dependent renal failure. Combination prophylaxis should be incorporated for all high-risk patients (emergent cases or patients with chronic kidney disease) and should be strongly considered for all interventional radio-contrast procedures.

The epidemiology and outcome of acute renal failure and the impact on chronic kidney disease.

Acute renal failure (ARF) is a common condition, especially among the critically ill, and confers a high mortality. Recent publications have highlighted changes in the epidemiology and improvement in mortality that was long thought to be static despite improvements in clinical care. The incidence of ARF is increasing. Efforts, such as the Acute Dialysis Quality Initiative, are being undertaken to establish a consensus definition of ARF, and to distinguish between varying degrees of acute kidney injury. Data are emerging to allow comparison of the epidemiology of ARF across institutions internationally. There is ongoing recognition of the important interaction between ARF and chronic kidney disease. Two brief case reports are offered to help frame the context and clinical impact of this disorder, followed by a review of some of the recent literature that addresses these points.

Acid-base disturbances in the intensive care unit: metabolic acidosis.

This article will discuss metabolic acidosis and, to a lesser extent, metabolic alkalosis in the ICU setting. A classification and clinical approach will be the focus.