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.

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.

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.

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.

Clinical Experience With IV Angiotensin II Administration: A Systematic Review of Safety.

OBJECTIVE: Angiotensin II is an endogenous hormone with vasopressor and endocrine activities. This is a systematic review of the safety of IV angiotensin II. DATA SOURCES: PubMed, Medline, Scopus, and Cochrane. STUDY SELECTION: Studies in which human subjects received IV angiotensin II were selected whether or not safety was discussed. DATA EXTRACTION: In total, 18,468 studies were screened by two reviewers and one arbiter. One thousand one hundred twenty-four studies, in which 31,281 participants received angiotensin II (0.5-3,780 ng/kg/min), were selected. Data recorded included number of subjects, comorbidities, angiotensin II dose and duration, pressor effects, other physiologic and side effects, and adverse events. DATA SYNTHESIS: The most common nonpressor effects included changes in plasma aldosterone, renal function, cardiac variables, and electrolytes. Adverse events were infrequent and included headache, chest pressure, and orthostatic symptoms. The most serious side effects were exacerbation of left ventricular failure in patients with congestive heart failure and bronchoconstriction. One patient with congestive heart failure died from refractory left ventricular failure. Refractory hypotensive shock was fatal in 55 of 115 patients treated with angiotensin II in case studies, cohort studies, and one placebo-controlled study. One healthy subject died after a pressor dose of angiotensin II was infused continuously for 6 days. No other serious adverse events attributable to angiotensin II were reported. Heterogeneity in study design prevented meta-analysis. CONCLUSION: Adverse events associated with angiotensin II were infrequent; however, exacerbation of asthma and congestive heart failure and one fatal cerebral hemorrhage were reported. This systematic review supports the notion that angiotensin II has an acceptable safety profile for use in humans.

Predicting acute kidney injury prognosis.

PURPOSE OF REVIEW: The incidence of acute kidney injury has been steadily increasing. The development of any degree of kidney injury is associated with worse outcomes. Therefore, the ability to risk stratify patients and to predict prognosis is essential to properly educate the patient and family, appropriately utilize healthcare resources, and provide therapeutic interventions that may improve outcomes. RECENT FINDINGS: Numerous biomarkers and clinical prediction models have been developed that improve our ability to predict which patients will progress to higher stages of chronic kidney disease, require dialysis, or survive. The integration of biomarkers in predictive models will likely provide the best information. Further investigation will be required to validate the utility of these tools. SUMMARY: Early risk stratification for acute kidney injury can aid clinical decision making. The use of various biomarkers and predictive clinical models will improve the ability to appropriately utilize resources and provide useful prognostic information.

Association Between Cognitive Impairment and Chronic Kidney Disease in Mexican Americans.

OBJECTIVES: To analyze the association between chronic kidney disease (CKD) and mild cognitive impairment (MCI) in Mexican Americans and to determine whether there is a blood-based proteomic profile linking CKD to MCI. DESIGN: Retrospective analysis of cohort study. SETTING: Health and Aging Brain among Latino Elders study. PARTICIPANTS: Mexican Americans (N = 437, 105 men, 332 women). MEASUREMENTS: Data were analyzed to examine the link between estimated glomerular filtration rate (eGFR) and detailed neuropsychological functioning. Serum proteomic markers were also examined. RESULTS: Lower eGFR levels were associated with significantly poorer neuropsychological functioning across multiple domains. After adjusting for age, sex, education, and diabetes mellitus, participants with an eGFR less than 45 mL/min per 1.73 m(2) performed significantly worse than those with an eGFR from 45 to 59 mL/min per 1.73 m(2) or 60 mL/min per 1.73 m(2) and higher in processing speed (F = 14.1, P < .001), executive functioning (F = 4.5, P = .01), visuospatial skills (F = 4.8, P = .009), and global cognitive functioning (F = 6.2, P = .002). Participants with an eGFR less than 45 mL/min per 1.73 m(2) also performed significantly worse than those with an eGFR of 60 mL/min per 1.73 m(2) or greater on delayed memory (F = 3.8, P = .02). There was a trend toward lower eGFR levels being associated with greater risk of MCI (odds ratio (OR) = 2.4, 95% confidence interval (CI) = 0.91-6.1, P = .07), which was stronger for men (OR = 9.6, 95% CI = 1.3-74.3, P = .03). A serum proteomic profile consisting of Factor VII, interleukin-10, C-reactive protein, and fatty acid binding protein was 93% accurate in detecting CKD-related MCI. CONCLUSION: Lower eGFR was associated with significantly poorer neuropsychological functioning in Mexican Americans. A blood-based profile was generated that was highly accurate in detecting CKD-related MCI. A blood profile capable of predicting CKD-related cognitive impairment would be of benefit for the design of clinical interventions.

Pitfalls in dosing vancomycin.

BACKGROUND: Vancomycin is a frequently used antibiotic for the treatment of methicillin-resistant gram-positive bacteria. Newer guidelines suggest dosing vancomycin to achieve a trough concentration between 15 and 20 mg/L. Achieving this higher concentration requires greater doses of the antibiotic. Even when using a nomogram, these higher doses often result in excessively elevated trough levels and increase the risk for vancomycin-associated acute kidney injury. We undertook this quality improvement project to better understand the reasons contributing to a toxic vancomycin trough level. METHODS: Over a 9-month period, we examined all vancomycin trough concentrations greater than 25 mg/L to determine their cause. RESULTS: Fifty-four elevated levels were identified in 38 patients. In 47 instances, adequate data were available for analysis. We could classify the etiology of the excessive levels into 4 groups: (1) incorrect timing of the blood collection, (2) improper dosing, (3) changing renal function and (4) abnormal pharmacokinetics/pharmacodynamics. CONCLUSIONS: Educational programs could correct the first 3 problems. However, only more frequent therapeutic drug monitoring or use of another, less toxic, antibiotic would remedy the last one.

A case report of defective endogenous vitamin D: a new clinical entity.

OBJECTIVE: To report a case of defective endogenous vitamin D with excellent response to low dose calcitriol replacement therapy. METHODS: We describe the patient's clinical presentation, biochemical workup, and clinical course. RESULTS: The patient initially presented with severe symptomatic hypocalcemia and was diagnosed with pseudohypoparathyroidism type 1b at an outside hospital and started on calcitriol 2.25 mcg twice daily with good response but calcitriol was stopped later for cost concerns which led to recurrence of symptoms, worsening hypocalcemia and increased parathormone levels. On review of her case it was noted that her 1,25 dihydroxy: vitamin D level was within normal limits even before she started taking calcitriol, which is not consistent with pseudohypoparathyroidism type 1b. Restarting low dose calcitriol (0.25 mcg twice daily) improved the patient's calcium level to 10.1 mg/dl and decreased the parathormone level to 17 pg/ml and symptoms resolved. Conditions associated with low serum calcium and high parathormone include pseudohypoparathyroidism, vitamin D deficiency and vitamin D resistance. This patient does not fit into any of the known entities causing hypocalcemia and elevated parathormone. CONCLUSIONS: We hypothesize that this patient had an inadequate number of vitamin D receptors that was corrected by exogenous administration of vitamin D.