Acid-Base Disorders in the Critically Ill Patient.

Acid-base disorders are common in the intensive care unit. By utilizing a systematic approach to their diagnosis, it is easy to identify both simple and mixed disturbances. These disorders are divided into four major categories: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. Metabolic acidosis is subdivided into anion gap and non-gap acidosis. Distinguishing between these is helpful in establishing the cause of the acidosis. Anion gap acidosis, caused by the accumulation of organic anions from sepsis, diabetes, alcohol use, and numerous drugs and toxins, is usually present on admission to the intensive care unit. Lactic acidosis from decreased delivery or utilization of oxygen is associated with increased mortality. This is likely secondary to the disease process, as opposed to the degree of acidemia. Treatment of an anion gap acidosis is aimed at the underlying disease or removal of the toxin. The use of therapy to normalize the pH is controversial. Non-gap acidoses result from disorders of renal tubular H + transport, decreased renal ammonia secretion, gastrointestinal and kidney losses of bicarbonate, dilution of serum bicarbonate from excessive intravenous fluid administration, or addition of hydrochloric acid. Metabolic alkalosis is the most common acid-base disorder found in patients who are critically ill, and most often occurs after admission to the intensive care unit. Its etiology is most often secondary to the aggressive therapeutic interventions used to treat shock, acidemia, volume overload, severe coagulopathy, respiratory failure, and AKI. Treatment consists of volume resuscitation and repletion of potassium deficits. Aggressive lowering of the pH is usually not necessary. Respiratory disorders are caused by either decreased or increased minute ventilation. The use of permissive hypercapnia to prevent barotrauma has become the standard of care. The use of bicarbonate to correct the acidemia is not recommended. In patients at the extreme, the use of extracorporeal therapies to remove CO 2 can be considered.

Use of synchronous kidney and lung extracorporeal support for severe COVID-19: A single-center retrospective study.

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus disease 2019 (COVID-19) has been associated with both kidney and respiratory failure. During the early phase of the coronavirus disease pandemic, patients often required the use of mechanical assistance to provide adequate kidney and lung function. In this paper we describe the clinical outcomes of patients who required synchronous kidney and lung extracorporeal support for COVID-19. MATERIALS AND METHODS: All patients admitted to Baylor University Medical Center, Dallas, between February 1, 2020, to April 23, 2021, with COVID-19 who required both extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) were retrospectively analyzed. Patients who were on hemo- or peritoneal dialysis prior to admission or who required veno-arterial (VA) ECMO were excluded. RESULTS: 35 patients with COVID-19 required ECMO and CRRT support. Four patients (11%) were excluded, 2 due to being on dialysis prior to admission and 2 due to the requirement of VA-ECMO. The median time on CRRT was 33 days (IQR 13 - 51). The median time on ECMO was 28 days (IQR 10.5 - 59.5). At 90 days, 9 patients had died (29%), 4 patients remained hospitalized, and 18 patients had been discharged: 10 to long-term acute care, 2 to inpatient rehabilitation, and 6 to home. CONCLUSION: Patients with severe COVID-19 requiring concurrent ECMO and CRRT in this institution had a 29% mortality at 90 days.

A Multicenter Evaluation of the Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19.

The Seraph100 Microbind Affinity Blood Filter (Seraph 100) (ExThera Medical, Martinez, CA) is an extracorporeal therapy that can remove pathogens from blood, including severe acute respiratory syndrome coronavirus 2. The aim of this study was to evaluate safety and efficacy of Seraph 100 treatment for COVID-19. DESIGN: Retrospective cohort study. SETTING: Nine participating ICUs. PATIENTS: COVID-19 patients treated with Seraph 100 (n = 53) and control patients matched by study site (n = 53). INTERVENTION: Treatment with Seraph 100. MEASUREMENTS AND MAIN RESULTS: At baseline, there were no differences between the groups in terms of sex, race/ethnicity, body mass index, and need for mechanical ventilation. However, patients in the Seraph 100 group were younger (median age, 54 yr; interquartile range [IQR], 41-65) compared with controls (median age, 64 yr; IQR, 56-69; p = 0.009). Charlson comorbidity index scores were lower in the Seraph 100 group (2; IQR, 0-3) compared with the control group (3; IQR, 2-4; p = 0.006). Acute Physiology and Chronic Health Evaluation II scores were also lower in Seraph 100 subjects (12; IQR, 9-17) compared with controls (16; IQR, 12-21; p = 0.011). The Seraph 100 group had higher vasopressor-free days with an incidence rate ratio of 1.30 on univariate analysis. This difference was not significant after adjustment. Seraph 100-treated subjects were less likely to die compared with controls (32.1% vs 64.2%; p = 0.001), a difference that remained significant after adjustment. However, no difference in mortality was observed in a post hoc analysis utilizing an external control group. In the full cohort of 86 treated patients, there were 177 total treatments, in which only three serious adverse events were recorded. CONCLUSIONS: Although this study did not demonstrate consistently significant clinical benefit across all endpoints and comparisons, the findings suggest that broad spectrum, pathogen agnostic, blood purification can be safely deployed to meet new pathogen threats while awaiting targeted therapies and vaccines.

Real-World Management of Hyperkalemia in the Emergency Department: An Electronic Medical Record Analysis.

INTRODUCTION: Hyperkalemia is often managed in the emergency department (ED) and it is important to understand how ED management and post-discharge outcomes vary by hyperkalemia severity. This study was conducted to characterize ED management and post-discharge outcomes across hyperkalemia severities. METHODS: Adults with an ED visit with hyperkalemia (at least one serum potassium lab measure above 5.0 mEq/L) were selected from US electronic medical record data (2012-2018). Patient characteristics, potassium levels, treatments, and monitoring prior to and during the ED visit were compared by hyperkalemia severity (mild [> 5.0-5.5 mEq/L], moderate [> 5.5-6.0], severe [> 6.0]) using unadjusted analyses. Death, immediate inpatient admission, 30-day hyperkalemia recurrence, and 30-day inpatient admission were also assessed by severity. RESULTS: Of 6222 patients included, 4432 (71.2%) had mild hyperkalemia, 1085 (17.4%) had moderate, and 705 (11.3%) had severe hyperkalemia. Chronic kidney disease (39.9-50.1%) and heart failure (21.6-24.3%) were common. In the ED, electrocardiograms (mild, 56.5%; moderate, 69.6%; severe, 81.0%) and patients with at least two potassium laboratory values increased with severity (15.0%; 40.4%; 75.5%). Among patients with at least two potassium laboratory values, over half of patients (60.4%) had potassium levels ≤ 5.0 mEq/L prior to discharge. Use of potassium-binding treatments (sodium polystyrene sulfonate: mild = 4.1%; moderate = 17.1%; severe = 27.4%), temporizing agents (5.6%; 15.5%; 31.6%), or dialysis (0.4%; 0.8%; 3.0%) increased with severity; treatment at discharge was not common. Death (1.1%; 3.7%; 10.6%), immediate admission to inpatient care (5.8%; 8.7%; 12.7%), 30-day hyperkalemia recurrence (2.9%; 19.0%; 32.5%), 30-day inpatient admission with hyperkalemia (6.5%; 7.9%; 9.3%) also increased with severity. CONCLUSION: Patients with moderate and severe hyperkalemia experienced elevated risk of hyperkalemia recurrence and hyperkalemia-related inpatient readmission following discharge from the ED from a descriptive analysis. Future research to assess strategies to reduce hyperkalemia recurrence and inpatient admission in this patient population would be beneficial.

Association of the COVID-19 pandemic with increased adherence among prevalent hemodialysis patients.

BACKGROUND: During the COVID-19 pandemic, there has been a reduction in emergency department visits and hospital admissions. We hypothesized that hemodialysis patients were decreasing their hospital visits and increasing their dialysis adherence during the COVID-19 pandemic. MATERIAL AND METHODS: This is a retrospective analysis of hemodialysis patients treated in the seven American Renal Associates (ARA) dialysis centers in the Dallas-Fort Worth metropolitan area. We conducted a "before-and-after" study using existing clinical data to examine patient adherence with hemodialysis between January 1 and March 14, 2020 (pre-COVID) and March 15 to May 18, 2020 (COVID) time periods. Data points included missed treatments, shortened treatments, post-dialysis weight, and hospital visits. Finally, we conducted an anonymous survey in which patients reported their hemodialysis adherence. RESULTS: Data analysis was performed on 556 patients. Significantly fewer patients missed a single treatment in the COVID vs. pre-COVID time periods (44.1 vs. 58.6%; p < 0.001). Significantly fewer patients finished their treatment with a post-dialysis weight more than 1 kg above their estimated dry weight in the COVID vs. pre-COVID time periods (31.7 vs. 38.9%, p = 0.01). Finally, there was a reduction in total hospital visits during the COVID vs. pre-COVID periods (12.6 vs. 19.4%; p = 0.002). The anonymous survey showed patients reporting increased adherence with hemodialysis and restriction of salt and water intake. CONCLUSION: The COVID time period was associated with increased adherence with hemodialysis and decreased hospital visits, and patients were conscious of these changes.

Determinants of Hyperkalemia Progression Among Patients with Mild Hyperkalemia.

INTRODUCTION: The progression of mild hyperkalemia and the predictors of progression have not been well characterized. In this study we aimed to characterize the progression of hyperkalemia and identify the risk factors for hyperkalemia progression. METHODS: Adults with mild hyperkalemia (at least one serum potassium measure > 5.0 and ≤ 5.5 mEq/L) were identified using electronic medical records from the Research Action for Health Network (2012-2018). Progression to moderate-to-severe and progression to severe hyperkalemia were defined as the first occurrences of a serum potassium measure > 5.5 and > 6.0 mEq/L, respectively. Kaplan-Meier analyses were conducted to estimate progression rates for all patients and by pre-specified patient subgroups. Hazard ratios (HR) of moderate-to-severe and severe hyperkalemia progression were estimated using Cox models. RESULTS: Of 35,369 patients with mild hyperkalemia, 16.9% and 8.7% progressed to moderate-to-severe and severe hyperkalemia, respectively. Rates of hyperkalemia progression elevated with the severity of chronic kidney disease (CKD). The highest progression rates were seen in patients with CKD stage 5 (stage 5 vs. no CKD: moderate-to-severe, 50.2% vs. 12.0%; severe, 31.3% vs. 3.9%; p < 0.001). Higher progression rates were also observed in patients with heart failure, hypertension, and type II diabetes compared with patients without those conditions (all p < 0.001). The most prominent risk factors were CKD stage 5 (HR of progression to moderate-to-severe hyperkalemia, 3.32 [95% CI 3.03-3.64]; severe, 4.08 [3.55-4.69]), CKD stage 4 (2.19 [1.97-2.43], 2.28 [1.92-2.71]), CKD stage 3 (1.57 [1.46-1.68], 1.65 [1.46-1.87]), type I diabetes (1.37 [1.18-1.61], 1.54 [1.23-1.93]), and serum potassium (1.12 [1.10-1.15], 1.13 [1.10-1.17] per 0.1 mEq/L increase) (all p values < 0.05). CONCLUSION: Hyperkalemia progression rates increased significantly with CKD stage and were also higher among patients with higher baseline potassium level, heart failure, hypertension, and diabetes.

Prevalence of Metabolic Acidosis Among Patients with Chronic Kidney Disease and Hyperkalemia.

INTRODUCTION: Although hyperkalemia and metabolic acidosis often co-occur in patients with chronic kidney disease (CKD), the prevalence of metabolic acidosis among patients with CKD and hyperkalemia is understudied. Therefore, we used medical record data from the Research Action for Health Network to estimate this prevalence. METHODS: Adult patients with CKD stage 3-5, ≥ 1 outpatient potassium value > 5.0 mEq/l, and ≥ 1 outpatient bicarbonate value available were identified. Patients with end stage kidney disease (ESKD) in the prior year were excluded. The prevalence of metabolic acidosis in each calendar year from 2014 to 2017 among patients with CKD and hyperkalemia was estimated using two definitions of hyperkalemia (potassium > 5.0 mEq/l and > 5.5 mEq/l) and metabolic acidosis (bicarbonate < 18 mEq/l and < 22 mEq/l). RESULTS: In the 2017 patient cohort and among patients with CKD and hyperkalemia, patients with metabolic acidosis were younger (69 versus 74 years), more likely to have advanced CKD (35% versus 13%), and use oral sodium bicarbonate (21% versus 4%) than patients without metabolic acidosis. The prevalence of metabolic acidosis (< 22 mEq/l) ranged from 25 to 29% when hyperkalemia was defined by potassium > 5.0 mEq/l and ranged from 33 to 39% when hyperkalemia was defined by potassium > 5.5 mEq/l. CONCLUSION: Results demonstrated that prevalence estimates of metabolic acidosis varied based on the definition of hyperkalemia and metabolic acidosis utilized.

Half the V by 120: A practical approach to the prevention of the dialysis disequilibrium syndrome.

The dialysis disequilibrium syndrome (DDS) results from osmotic shifts between the blood and the brain compartments. Patients at risk for DDS include those with very elevated blood urea nitrogen, concomitant hypernatremia, metabolic acidosis, and low total body water volumes. By understanding the underlying pathophysiology and applying urea kinetic modeling, it is possible to avoid the occurrence of this disorder. A urea reduction ratio (URR) of no more than 40%-45% over 2 h is recommended for the initial hemodialysis treatment. The relationship between the URR and Kt/V is useful when trying to model the dialysis treatment to a specific URR target. A simplified relationship between Kt/V and URR is provided by the equation: Kt/V = -ln (1 - URR). A URR of 40% is roughly equivalent to a Kt/V of 0.5. The required dialyzer urea clearance to achieve this goal URR in a 120-min treatment can simply be calculated by dividing half the patient's volume of distribution of urea by 120. The blood flow rate and dialyzer mass transfer coefficient (K0 A) required to achieve this clearance can then be plotted on a nomogram. Other methods to reduce the risk of DDS are reviewed, including the use of continuous renal replacement therapy.

Inpatient management and post-discharge outcomes of hyperkalemia.

OBJECTIVES: Patients with hyperkalemia are commonly treated in the inpatient setting; however, real-world evidence is limited. The purpose of this study was to describe the inpatient management and post-discharge outcomes among patients with hyperkalemia. METHODS: Electronic medical record data (2012-2018) were used to analyze US adult patients with an inpatient stay with hyperkalemia (≥1 potassium value >5.0mEq/L). Patient characteristics, treatments, and monitoring six months prior to and during the inpatient stay, and hyperkalemia recurrence and inpatient readmissions post-discharge were summarized and compared among patients with mild (>5.0-5.5mEq/L), moderate (>5.5-6.0), and severe (>6.0) hyperkalemia. RESULTS: Of the 21,793 patients, 69.2% had mild, 19.0% had moderate, and 11.8% had severe hyperkalemia during inpatient care. The most common inpatient treatments were temporizing agents (mild: 28.9%; moderate: 46.0%; severe: 73.0%), diuretics (32.7%; 37.1%; 34.6%), and sodium-polystyrene sulfonate (11.7%; 27.8%; 45.3%). Almost no patients (0.1%) received a potassium binder at discharge. Most patients (86.8%) had their potassium levels return to ≤5.0mEq/L during the inpatient stay. Death during the inpatient stay occurred in 12.3% of mild, 15.5% of moderate, and 19.5% of severe hyperkalemic patients. Within 30 days of discharge, hyperkalemia recurred in 13.3%, 15.4%, and 18.4% of patients with mild, moderate, and severe hyperkalemia, respectively. Additionally, 19.7%, 21.5%, and 19.6% of patients were readmitted to inpatient care within 30 days post-discharge. CONCLUSION: Among patients with hyperkalemia in the inpatient setting, treatment and normalization of serum potassium levels were common. However, death, readmission, and hyperkalemia recurrence were also fairly common across all cohorts. Future studies examining measures to reduce inpatient death, readmission, and hyperkalemia recurrence among patients with hyperkalemia in inpatient care are warranted.

Angiotensin I and angiotensin II concentrations and their ratio in catecholamine-resistant vasodilatory shock.

BACKGROUND: In patients with vasodilatory shock, plasma concentrations of angiotensin I (ANG I) and II (ANG II) and their ratio may reflect differences in the response to severe vasodilation, provide novel insights into its biology, and predict clinical outcomes. The objective of these protocol prespecified and subsequent post hoc analyses was to assess the epidemiology and outcome associations of plasma ANG I and ANG II levels and their ratio in patients with catecholamine-resistant vasodilatory shock (CRVS) enrolled in the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study. METHODS: We measured ANG I and ANG II levels at baseline, calculated their ratio, and compared these results to values from healthy volunteers (controls). We dichotomized patients according to the median ANG I/II ratio (1.63) and compared demographics, clinical characteristics, and clinical outcomes. We constructed a Cox proportional hazards model to test the independent association of ANG I, ANG II, and their ratio with clinical outcomes. RESULTS: Median baseline ANG I level (253 pg/mL [interquartile range (IQR) 72.30-676.00 pg/mL] vs 42 pg/mL [IQR 30.46-87.34 pg/mL] in controls; P <  0.0001) and median ANG I/II ratio (1.63 [IQR 0.98-5.25] vs 0.4 [IQR 0.28-0.64] in controls; P <  0.0001) were elevated, whereas median ANG II levels were similar (84 pg/mL [IQR 23.85-299.50 pg/mL] vs 97 pg/mL [IQR 35.27-181.01 pg/mL] in controls; P = 0.9895). At baseline, patients with a ratio above the median (≥1.63) had higher ANG I levels (P <  0.0001), lower ANG II levels (P <  0.0001), higher albumin concentrations (P = 0.007), and greater incidence of recent (within 1 week) exposure to angiotensin-converting enzyme inhibitors (P <  0.00001), and they received a higher norepinephrine-equivalent dose (P = 0.003). In the placebo group, a baseline ANG I/II ratio <1.63 was associated with improved survival (hazard ratio 0.56; 95% confidence interval 0.36-0.88; P = 0.01) on unadjusted analyses. CONCLUSIONS: Patients with CRVS have elevated ANG I levels and ANG I/II ratios compared with healthy controls. In such patients, a high ANG I/II ratio is associated with greater norepinephrine requirements and is an independent predictor of mortality, thus providing a biological rationale for interventions aimed at its correction. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02338843. Registered 14 January 2015.

Hydralazine-induced pericardial effusion.

Drug-induced lupus (DIL) is due to an autoimmune reaction to a drug with an estimated incidence of 15,000 to 30,000 cases every year in the US. Hydralazine is a well-known offender. Antinuclear antibody (ANA) is present in most cases, though four cases of ANA-negative DIL have been reported. In this report, we present another case of ANA-negative DIL secondary to hydralazine.

Icosapent ethyl reduces atherogenic markers in high-risk statin-treated patients with stage 3 chronic kidney disease and high triglycerides.

Objective: Patients with chronic kidney disease (CKD) have increased cardiovascular disease (CVD) risk, likely driven by atherogenic and inflammatory markers beyond low-density lipoprotein cholesterol (LDL-C). The objective of this hypothesis-generating post hoc subgroup analysis was to explore the effects of icosapent ethyl at 2 or 4 g/day (prescription pure ethyl ester of the omega-3 fatty acid eicosapentaenoic acid [EPA]) on atherogenic lipid, apolipoprotein, inflammatory parameters (high-sensitivity C-reactive protein [hsCRP], lipoprotein-associated phospholipase A2 [Lp-PLA2]), and oxidative parameters (oxidized-LDL [ox-LDL]) in statin-treated patients from ANCHOR with stage 3 CKD.Methods: The 12-week ANCHOR study evaluated icosapent ethyl in 702 statin-treated patients at increased CVD risk with triglycerides (TG) 200-499 mg/dL despite controlled LDL-C (40-99 mg/dL). This post-hoc analysis included patients from ANCHOR with stage 3 CKD (estimated glomerular filtration rate [eGFR] ≤60 mL/min/1.73 m2 for ≥3 months) randomized to icosapent ethyl 4 g/day (n = 19), 2 g/day (n = 30), or placebo (n = 36).Results: At the prescription dose of 4 g/day, icosapent ethyl significantly reduced TG (-16.9%; P = 0.0074) and other potentially atherogenic lipids/lipoproteins, ox-LDL, hsCRP, and Lp-PLA2, and increased plasma and red blood cell EPA levels (+879% and +579%, respectively; both P < 0.0001) versus placebo. Icosapent ethyl did not significantly alter eGFR or serum creatinine. Safety and tolerability were similar to placebo.Conclusions: In patients with stage 3 CKD at high CVD risk with persistent high TG despite statins, icosapent ethyl 4 g/day reduced potentially atherogenic and other cardiovascular risk factors without raising LDL-C, with safety similar to placebo. These findings suggest prospective investigation may be warranted.

Partial Fanconi syndrome induced by ifosfamide.

Ifosfamide-induced proximal tubular nephropathy can present as a spectrum of disease, from isolated hyperaminoaciduria to a partial or complete Fanconi syndrome. We report a case of ifosfamide-induced partial Fanconi syndrome in a man with metastatic progressive Ewing sarcoma and put forth a hypothesis on the mechanism.

Euvolemia-A critical target in the management of acute kidney injury.

It has been clearly established that critically ill patients with sepsis require prompt fluid resuscitation. The optimal amount of fluid and when to taper this resuscitation is less clear. There is a growing evidence that fluid overload leads to acute kidney injury, and increased morbidity and mortality. A clinician's best intentions in resuscitating a patient can lead to too much of a good thing. Currently, there are several bedside tools to aid in determining a patient's response to a fluid challenge as well as in the assessment of the current volume status. Guidelines are not available on the exact rate of fluid overload removal and what medicinal or mechanical modality is most favorable. We discuss our experience and an examination of the literature on the problems with fluid overload, and how a patient may benefit from forced fluid removal.

Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II.

OBJECTIVE: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. DESIGN: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. SETTING: ICUs. PATIENTS: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo (n = 45 and n = 60, respectively). INTERVENTIONS: IV angiotensin II or placebo. MEASUREMENTS AND MAIN RESULTS: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%-67%) and 30% (95% CI, 19%-41%) in patients treated with angiotensin II and placebo (p = 0.012), respectively. By day 7, 38% (95% CI, 25%-54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%-27%) placebo (p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%-68%) and 22% (95% CI, 12%-34%) of patients treated with angiotensin II and placebo (p = 0.001), respectively. CONCLUSIONS: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.