Hyperkalemia is a common electrolyte disorder that can result in fatal cardiac arrhythmias. Despite the importance of insulin as a lifesaving intervention in the treatment of hyperkalemia in an ...emergency setting, there is no consensus on the dose or the method (bolus or infusion) of its administration. Our aim was to review data in the literature to determine the optimal dose and route of administration of insulin in the management of emergency hyperkalemia.
We searched several databases from their date of inception through February 2015 for eligible articles published in any language. We included any study that reported on the use of insulin in the management of hyperkalemia.
We identified eleven studies. In seven studies, 10 units of regular insulin was administered (bolus in five studies, infusion in two studies), in one study 12 units of regular insulin was infused over 30 minutes, and in three studies 20 units of regular insulin was infused over 60 minutes. The majority of included studies were biased. There was no statistically significant difference in mean decrease in serum potassium (K+) concentration at 60 minutes between studies in which insulin was administered as an infusion of 20 units over 60 minutes and studies in which 10 units of insulin was administered as a bolus (0.79±0.25 mmol/L versus 0.78±0.25 mmol/L, P = 0.98) or studies in which 10 units of insulin was administered as an infusion (0.79±0.25 mmol/L versus 0.39±0.09 mmol/L, P = 0.1). Almost one fifth of the study population experienced an episode of hypoglycemia.
The limited data available in the literature shows no statistically significant difference between the different regimens of insulin used to acutely lower serum K+ concentration. Accordingly, 10 units of short acting insulin given intravenously may be used in cases of hyperkalemia. Alternatively, 20 units of short acting insulin may be given as a continuous intravenous infusion over 60 minutes in patients with severe hyperkalemia (i.e., serum K+ concentration > 6.5 mmol/L) and those with marked EKG changes related to hyperkalemia (e.g., prolonged PR interval, wide QRS complex) as an alternative to 10 units of short acting insulin. Because the risk of hypoglycemia is increased with using large insulin doses, sufficient glucose (60 grams with the administration of 20 units of insulin and 50 grams with the administration of 10 units) should be given to prevent hypoglycemia, and plasma glucose should be frequently monitored.
Abstract Background Sodium polystyrene sulfonate (Kayexalate; Sanofi-Aventis, Paris, France) is a cation-exchange resin routinely used in the management of hyperkalemia. However, its use has been ...associated with colonic necrosis and other fatal gastrointestinal adverse events. Although the addition of sorbitol to sodium polystyrene sulfonate preparations was previously believed to be the cause of gastrointestinal injury, recent reports have suggested that sodium polystyrene sulfonate itself may be toxic. Our objective was to systematically review case reports of adverse gastrointestinal events associated with sodium polystyrene sulfonate use. Methods MEDLINE (1948 to July 2011), EMBASE (1980 to July 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (1993 to July 27, 2011), bibliographies of identified articles, and websites of relevant drug agencies and professional associations in the United States and Canada were reviewed to identify eligible reports of adverse gastrointestinal events associated with sodium polystyrene sulfonate use. Causality criteria of the World Health Organization causality assessment system were applied to each report. Results Thirty reports describing 58 cases (41 preparations containing sorbitol and 17 preparations without sorbitol) of adverse events were identified. The colon was the most common site of injury (n = 44; 76%), and transmural necrosis (n = 36; 62%) was the most common histopathologic lesion reported. Mortality was reported in 33% of these cases due to gastrointestinal injury. Conclusions Sodium polystyrene sulfonate use, both with and without sorbitol, may be associated with fatal gastrointestinal injury. Physicians must be cognizant of the risk of these adverse events when prescribing this therapy for the management of hyperkalemia.
Background Dialysis-requiring acute kidney injury (AKI) is common among critically ill patients, but little is known about trends in the incidence and outcomes of this condition over time. Study ...Design Population-based cohort study. Setting & Participants All adult patients admitted to an intensive care unit in Ontario, Canada, 1996 to 2010. Predictor Year and era (1996-2000, 2001-2005, and 2006-2010) of cohort entry. Outcomes Mortality and dialysis dependence, each evaluated at 90 and 365 days after initiation of dialysis therapy for AKI. Measurements The annual incidence proportion of dialysis-requiring AKI was evaluated and patients with this condition were characterized by era. Associations between era and the outcomes of interest were evaluated with Cox proportional hazards (for time to death) and logistic regression (for dialysis dependence), with adjustment for relevant demographic and clinical variables. Results The annual incidence of dialysis-requiring AKI among critically ill patients increased from 0.8% in 1996 to 3.0% in 2010 ( P for trend < 0.001). 90-day mortality declined from 50% in 1996 to 2000 to 45% in 2006 to 2010 (adjusted HR, 0.83 95% CI, 0.79-0.87 compared to 1996-2000). Dialysis dependence among surviving patients at 90 days was marginally lower in 2006 to 2010 (25.1%) compared to 1996 to 2000 (27.2%), but after adjustment for confounding factors, was not significantly different (adjusted OR, 0.91; 95% CI, 0.80-1.03). Limitations Unmeasured confounding by factors that may have changed in patients with dialysis-requiring AKI during the different eras; data set does not allow for mechanistic explanation for the findings; and lack of access to laboratory investigations after hospital discharge. Conclusions The incidence proportion of dialysis-requiring AKI among critically ill patients increased by almost 4-fold between 1996 and 2010. This was accompanied by a significant decline in mortality, but the risk of long-term dialysis dependence continues to affect a substantial minority of surviving patients with no clear evidence of improvement over time.
Survivors of severe acute kidney injury remain at high risk of death well after apparent recovery from the initial insult. Here we determine whether early nephrology follow-up after a hospitalization ...complicated by severe acute kidney injury associates with patient survival. This consisted of a cohort study of all hospitalized adults in Ontario from 1996 to 2008 with acute kidney injury who received temporary inpatient dialysis and survived for 90 days following discharge independent from dialysis. Propensity scores were used to match individuals with early nephrology follow-up, defined as a visit with a nephrologist within 90 days of discharge, to those without. The outcome was time to all-cause mortality of 3877 patients who met the eligibility criteria within a maximum follow-up of 2 years. A total of 1583 patients had early nephrology follow-up of whom 1184 were successfully matched 1:1 to those not receiving early follow-up. The incidence of all-cause mortality was lower in those patients with early nephrology follow-up compared with those without (8.4 compared with 10.6 per 100-patient years, hazard ratio 0.76 (95% CI: 0.62–0.93)). Thus, early nephrology follow-up after hospitalization with acute kidney injury and temporary dialysis was associated with improved survival. This finding requires definitive testing in a randomized controlled trial.
Immune checkpoint inhibitors (ICIs) are increasingly used to treat cancers. Kidney immune-related adverse events (IRAEs) are now well recognized, with the incidence of IRAEs ranging from 2% to 5%. ...Most of the initial data related to kidney IRAEs have focused on acute interstitial nephritis (AIN). There are minimal data on the types and relative frequencies of glomerular diseases associated with ICIs, their treatment, and outcomes.
We performed a systematic review and meta-analysis of all biopsy-proven published cases/series of glomerular pathology associated with ICIs. We searched the MEDLINE, EMBASE, and Cochrane databases from inception to February 2020. We abstracted patient-level data, including demographics, cancer and ICI therapy details, and characteristics of kidney injury.
After screening, 27 articles with 45 cases of biopsy-confirmed ICI-associated glomerular disease were identified. Several lesion types were observed, with the most frequent being pauci-immune glomerulonephritis (GN) and renal vasculitis (27%), podocytopathies (24%), and complement 3 GN (C3GN; 11%). Concomitant AIN was reported in 41%. Most patients had ICIs discontinued (88%), and nearly all received corticosteroid treatment (98%). Renal replacement therapy (RRT) was required in 25%. Most patients had full (31%) or partial (42%) recovery from acute kidney injury (AKI), although 19% remained dialysis-dependent, and approximately one-third died. Complete or partial remission of proteinuria was achieved in 45% and 38%, respectively.
Multiple forms of ICI-associated glomerular disease have been described. Pauci-immune GN, podocytopathies, and C3GN are the most frequently reported lesions. ICI-associated glomerular disease may be associated with poor kidney and mortality outcomes. Oncologists and nephrologists must be aware of glomerular pathologies associated with ICIs and consider obtaining a kidney biopsy specimen when features atypical for AIN are present.
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The relation between prepregnancy average glucose concentration and a woman's risk of severe maternal morbidity (SMM) is unknown. The current study evaluated whether an elevated preconception ...hemoglobin A1c (A1c) is associated with SMM or maternal death among women with and without known prepregnancy diabetes mellitus (DM).
A population-based cohort study was completed in Ontario, Canada, where there is universal healthcare. The main cohort included 31,225 women aged 16-50 years with a hospital live birth or stillbirth from 2007 to 2015, and who had an A1c measured within 90 days before conception, including 28,075 women (90%) without known prepregnancy DM. The main outcome was SMM or maternal mortality from 23 weeks' gestation up to 42 days postpartum. Relative risks (RRs) were generated using modified Poisson regression, adjusting for the main covariates of maternal age, multifetal pregnancy, world region of origin, and tobacco/drug dependence. The mean maternal age was 31.1 years. Overall, SMM or death arose among 682 births (2.2%). The RR of SMM or death was 1.16 (95% CI 1.14-1.19; p < 0.001) per 0.5% increase in A1c and 1.16 (95% CI 1.13-1.18; p < 0.001) after adjusting for the main covariates. The adjusted relative risk (aRR) was increased among those with (1.11, 95% CI 1.07-1.14; p < 0.001) and without (1.15, 95% CI 1.02-1.29; p < 0.001) known prepregnancy diabetes, and upon further adjusting for body mass index (BMI) (1.15, 95% CI 1.11-1.20; p < 0.001), or chronic hypertension and prepregnancy serum creatinine (1.11, 95% CI 1.04-1.18; p = 0.002). The aRR of SMM or death was 1.31 (95% CI 1.06-1.62; p = 0.01) in those with a preconception A1c of 5.8%-6.4%, and 2.84 (95% CI 2.31-3.49; p < 0.001) at an A1c > 6.4%, each relative to an A1c < 5.8%. Among those without previously recognized prepregnancy diabetes and whose A1c was >6.4%, the aRR of SMM or death was 3.25 (95% CI 1.76-6.00; p < 0.001). Study limitations include that selection bias may have incorporated less healthy women tested for A1c, and BMI was unknown for many women.
Our findings indicate that women with an elevated A1c preconception may be at higher risk of SMM or death in pregnancy or postpartum, including those without known prepregnancy DM.
Abstract Background Acute kidney injury frequently arises within an acute care hospitalization. Outcomes among acute kidney injury survivors following hospital discharge are poorly documented. ...Methods We conducted a population-based cohort study between 1996 and 2006 of all adult patients in Ontario with acute kidney injury who did not require in-hospital dialysis, and who survived free of dialysis ≥30 days after discharge. Those with acute kidney injury (n = 41,327) were matched 1:1 to patients without acute kidney injury during their index hospitalization. Matching was by age (±1 year), sex, history of chronic kidney disease, receipt of mechanical ventilation during the index hospitalization, and a propensity score for developing acute kidney injury. The primary outcome was subsequent need for chronic dialysis. The secondary outcomes were all-cause mortality and rehospitalization. Results Mean age was 70 years, and median follow-up was 2 years (maximum 10 years). The incidence of chronic dialysis was 1.78 per 100 person-years among those with acute kidney injury and 0.74 per 100 person-years among unaffected controls (adjusted hazard ratio HR; 2.70, 95% confidence interval CI, 2.42-3.00). Rates also were higher for all-cause mortality (15.34 vs 14.51 per-100 person-years; adjusted HR 1.10; 95% CI, 1.07-1.13) and rehospitalization (44.93 vs 37.18 per 100 person-years; adjusted HR 1.21; 95% CI, 1.18-1.24). Conclusion Even when acute dialysis is not required, survivors of acute kidney injury remain at higher risk of receipt of chronic dialysis thereafter. The absolute risk of death was more than 8 times the rate of chronic dialysis.
Abstract Background The risk of hospital readmission in acute kidney injury survivors is not well understood. We estimated the proportion of acute kidney injury patients who were rehospitalized ...within 30 days and identified characteristics associated with hospital readmission. Methods We conducted a population-based study of patients who survived a hospitalization complicated by acute kidney injury from 2003-2013 in Ontario, Canada. The primary outcome was 30-day hospital readmission. We used a propensity score model to match patients with and without acute kidney injury, and a Cox proportional hazards model with death as a competing risk to identify predictors of 30-day readmission. Results We identified 156,690 patients who were discharged from 197 hospitals after an episode of acute kidney injury. In the subsequent 30 days, 27,457 (18%) patients were readmitted; 15,988 (10%) visited the emergency department and 7480 (5%) died. We successfully matched 111,778 patients with acute kidney injury 1:1 to patients without acute kidney injury. The likelihood of 30-day readmission was higher in acute kidney injury patients than those without acute kidney injury (hazard ratio HR 1.53; 95% confidence interval CI, 1.50-1.57). Factors most strongly associated with 30-day rehospitalization were the number of hospitalizations in the preceding year (adjusted HR 1.45 for ≥2 hospitalizations; 95% CI, 1.40-1.51) and receipt of inpatient chemotherapy (adjusted HR 1.44; 95% CI, 1.32-1.58). Conclusions One in 5 patients who survive a hospitalization complicated by acute kidney injury is readmitted in the next 30 days. Better strategies are needed to identify and care for acute kidney injury survivors in the community.
Abstract Background Patients with atrial fibrillation receiving dialysis are at a high risk of ischemic stroke. The role of warfarin in mitigating this risk in patients with atrial fibrillation ...receiving dialysis is uncertain. Our objective was to examine the safety and efficacy of warfarin in patients who have atrial fibrillation and are receiving dialysis. Methods We used Medline, Embase, and the Cochrane Library to conduct a systematic review and meta-analysis of published and unpublished observational and interventional studies relating to the use of warfarin in patients with atrial fibrillation receiving dialysis, which provided data on the risk of stroke and/or bleeding outcomes relative to placebo or no anticoagulation therapy. A random effects model was used to calculate pooled adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for these outcomes. Results No randomized controlled trials met the criteria for inclusion. Fourteen observational studies (20,398 participants) were included in the analysis. The use of warfarin was not associated with ischemic stroke (14 studies; 20,398 participants, aHR 0.77, 95% CI 0.55 to 1.07), intracranial hemorrhage (hemorrhagic stroke) (4 studies; 15,726 participants, aHR 1.93, 95% CI 0.93-4.00), gastrointestinal bleeding (3 studies, 14,693 participants, aHR 1.19, 95% CI 0.8-1.76) or all-cause mortality (7 studies; 16,172 participants, aHR 0.89, 95% CI 0.72-1.11). Conclusion Observational studies suggest that warfarin was not associated with a clear benefit or harm among patients who have atrial fibrillation and are receiving dialysis. These estimates were limited by study heterogeneity including the inability to account for a number of important confounders such as the time in the therapeutic range. Given the high prevalence of atrial fibrillation, stroke, and bleeding complications in this population, well-designed clinical trials of warfarin and other anti-coagulants are urgently needed.
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