The impact of muscle mass and myosteatosis on mortality in critically ill patients with Sars-Cov2-related pneumonia.

BACKGROUND & AIMS: Sars-Cov-2 pneumonia can lead to severe complications, requiring invasive mechanical ventilation and admission to the intensive care unit (ICU). Low muscle quantity and quality (the latter evaluated by the amount of ectopic fat infiltration in the muscle [myosteatosis]) at ICU admission are associated with worse outcomes in critically ill patients. The purpose of the present study is to assess muscle mass and myosteatosis of paravertebral skeletal muscle, in critically ill patients with Sars-Cov2 pneumonia and its association with mortality. METHODS: We conducted a retrospective observational study in 110 critically ill patients with severe Sars-Cov-2 pneumonia that had a high - resolution chest Computerized Tomography (HR-CT) at ICU admission. We acquired CT images at the level of the thoracic 12 (T12) vertebral body and measured skeletal muscle area (SMA), intermuscular adipose tissue (IMAT), and low attenuation muscle area (LAMA). Patients were followed until ICU mortality or discharge. RESULTS: Patients were 59.8 ± 8.1 years old, 77% were male. Seventy-nine percent of patients were considered at nutritional risk, and 22% were obese. Average Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 17 ± 5.4, and the overall ICU mortality was 48,2% (53/110). At ICU admission, both parameters of myosteatosis were associated with higher mortality (IMAT [per 10% increase] HR: 2.01 (95% Confidence Interval [CI] 1.27 to 3.17), P = 0.003; LAMA HR [per 10% increase]: 1.53 (95% CI 1.10 to 2.13), P = 0.012). CONCLUSION: Myosteatosis as assessed by CT scans plays a relevant role as a prognostic marker in critically ill patients with Sars-Cov2 severe pneumonia.

Treatment of dabigatran intoxication in critically ill patients with Acute Kidney Injury: The role of Sustained Low-Efficiency Dialysis.

The use of dabigatran in patients with non-valvular atrial fibrillation (AF) has widely increased in the last decades, due to its positive effects in terms of safety/efficacy. However, because of the risk of major bleeding, a great degree of attention has been suggested in elderly patients with multiple comorbidities. Notably, dabigatran mainly undergoes renal elimination and dose adjustment is recommended in patients with Chronic Kidney Disease (CKD). In this regard, the onset of an abrupt decrease of kidney function may further affect dabigatran pharmacokinetic profile, increasing the risk of acute intoxication. Idarucizumab is the approved antagonist in the case of dabigatran-associated major bleeding or concomitant need of urgent surgery, but its clinical use is limited by the lack of data in patients with Acute Kidney Injury (AKI). Thus, the early start of Extracorporeal Kidney Replacement Therapy (EKRT) could be indicated to remove the drug and to reverse the associated excess anticoagulation. Sustained Low-Efficiency Dialysis (SLED) could represent an effective therapeutic option to reduce the dabigatran plasma levels rapidly while avoiding post-treatment rebound. We present here a case series of three AKI patients with acute dabigatran intoxication, effectively and safely resolved with a single SLED session.

Regional citrate anticoagulation (RCA) in critically ill patients undergoing renal replacement therapy (RRT): expert opinion from the SIAARTI-SIN joint commission.

Renal replacement therapies (RRT) are essential to support critically ill patients with severe acute kidney injury (AKI), providing control of solutes, fluid balance and acid-base status. To maintain the patency of the extracorporeal circuit, minimizing downtime periods and blood losses due to filter clotting, an effective anticoagulation strategy is required.Regional citrate anticoagulation (RCA) has been introduced in clinical practice for continuous RRT (CRRT) in the early 1990s and has had a progressively wider acceptance in parallel to the development of simplified systems and safe protocols. Main guidelines on AKI support the use of RCA as the first line anticoagulation strategy during CRRT in patients without contraindications to citrate and regardless of the patient's bleeding risk.Experts from the SIAARTI-SIN joint commission have prepared this position statement which discusses the use of RCA in different RRT modalities also in combination with other extracorporeal organ support systems. Furthermore, advise is provided on potential limitations to the use of RCA in high-risk patients with particular attention to the need for a rigorous monitoring in complex clinical settings. Finally, the main findings about the prospective of optimization of RRT solutions aimed at preventing electrolyte derangements during RCA are discussed in detail.

Simplified regional citrate anticoagulation protocol for CVVH, CVVHDF and SLED focused on the prevention of KRT-related hypophosphatemia while optimizing acid-base balance.

BACKGROUND: Hypophosphatemia is a common electrolyte disorder in critically ill patients undergoing prolonged kidney replacement therapy (KRT). We evaluated the efficacy and safety of a simplified regional citrate anticoagulation (RCA) protocol for continuous venovenous hemofiltration (CVVH), continuous venovenous hemodiafiltration (CVVHDF) and sustained low-efficiency dialysis filtration (SLED-f). We aimed at preventing KRT-related hypophosphatemia while optimizing acid-base equilibrium. METHODS: KRT was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 filters (ST 150, 1.5 m2, Baxter), combining a 18 mmol/L pre-dilution citrate solution (Regiocit 18/0, Baxter) with a phosphate-containing solution (HPO42- 1.0 mmol/L, HCO3- 22.0 mmol/L; Biphozyl, Baxter). When needed, phosphate loss was replaced with sodium glycerophosphate pentahydrate (Glycophos™ 20 mmol/20 mL, Fresenius Kabi Norge AS, Halden, Norway). Serum citrate measurements were scheduled during each treatment. We analyzed data from three consecutive daily 8-h SLED-f sessions, as well as single 72-h CVVH or 72-h CVVHDF sessions. We used analysis of variance (ANOVA) for repeated measures to evaluate differences in variables means (i.e. serum phosphate, citrate). Because some patients received phosphate supplementation, we performed analysis of covariance (ANCOVA) for repeated measures modelling phosphate supplementation as a covariate. RESULTS: Forty-seven patients with acute kidney injury (AKI) or end stage kidney disease (ESKD) requiring KRT were included [11 CVVH, 11 CVVHDF and 25 SLED-f sessions; mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score 25 ± 7.0]. Interruptions for irreversible filter clotting were negligible. The overall incidence of hypophosphatemia (s-P levels <2.5 mg/dL) was 6.6%, and s-P levels were kept in the normality range irrespective of baseline values and the KRT modality. The acid-base balance was preserved, with no episode of citrate accumulation. CONCLUSIONS: Our data obtained with a new simplified RCA protocol suggest that it is effective and safe for CVVH, CVVHDF and SLED, allowing to prevent KRT-related hypophosphatemia and maintain the acid-base balance without citrate accumulation. TRIAL REGISTRATION: NCT03976440 (registered 6 June 2019).

Hypophosphatemia in critically ill patients undergoing Sustained Low-Efficiency Dialysis with standard dialysis solutions.

BACKGROUND: In patients admitted to the Intensive Care Unit (ICU), Kidney Replacement Therapy (KRT) is an important risk factor for hypophosphataemia. However, studies addressing the development of hypophosphatemia during prolonged intermittent KRT modalities are lacking. Thus, we evaluated the incidence of hypophosphatemia during Sustained Low-Efficiency Dialysis (SLED) in ICU patients; we also examined the determinants of post-SLED serum phosphate level (s-P) and the relation between s-P and phosphate supplementation and ICU mortality. METHODS: We conducted a retrospective analysis on a cohort of critically ill patients with severe renal failure and KRT need, who underwent at least three consecutive SLED sessions at 24-72 h time intervals with daily monitoring of s-P concentration. SLED with Regional Citrate Anticoagulation (RCA) was performed with either conventional dialysis machines or continuous-KRT monitors and standard dialysis solutions. When deemed necessary by the attending physician, intravenous phosphate supplementation was provided by sodium glycerophosphate pentahydrate. We used mixed-effect models to examine the determinants of s-P and Cox proportional hazards regression models with time-varying covariates to examine the adjusted relation between s-P, intravenous phosphate supplementation and ICU mortality. RESULTS: We included 65 patients [mean age 68 years (SD 10.0); mean Acute Physiology and Chronic Health Evaluation II score 25 (range 9-40)] who underwent 195 SLED sessions. The mean s-P before the start of the first SLED session (baseline s-P) was 5.6 ± 2.1 mg/dL (range 1.5-12.3). Serum phosphate levels at the end of each SLED decreased with increasing age, SLED duration and number of SLED sessions (P < .05 for all). The frequency of hypophosphatemia increased after the first through the third SLED session (P = .012). Intravenous phosphate supplementation was scheduled after 12/45 (26.7%) SLED sessions complicated by hypophosphataemia. The overall ICU mortality was 23.1% (15/65). In Cox regression models, after adjusting for potential confounders and for current s-P, intravenous phosphate supplementation was associated with a decrease in ICU mortality [adjusted hazard ratio: 0.24 (95% confidence interval: 0.06 to 0.89; P = 0.033)]. CONCLUSIONS: Hypophosphatemia is a frequent complication in critically ill patients undergoing SLED with standard dialysis solutions, that worsens with increasing SLED treatment intensity. In patients undergoing daily SLED, phosphate supplementation is strongly associated with reduced ICU mortality.

The Association of New-Onset Acute Kidney Injury and Mortality in Critically Ill Patients With COVID-19 With Less Severe Clinical Conditions at Admission: A Moderation Analysis.

Acute kidney injury (AKI), electrolyte, and acid-base disorders complicate the clinical course of critically ill patients with coronavirus-associated disease (COVID-19) and are associated with poor outcomes. It is not known whether the severity of clinical conditions at admission in the intensive care unit (ICU) changes the clinical significance of AKI and/or electrolyte or acid-base disorders developing during ICU stay. We conducted a retrospective study in critically ill patients with COVID-19 to evaluate whether the severity of clinical conditions at admission in the ICU affects the impact of AKI and of serum electrolytes or acid-base status on mortality. We carried out a 28-day retrospective follow-up study on 115 critically ill patients consecutively admitted to ICU for severe COVID-19 at a tertiary care university hospital and surviving longer than 24 h. We collected baseline demographic and clinical characteristics, and longitudinal data on kidney function, kidney replacement therapy, serum electrolytes, and acid-base status. We used Cox proportional hazards multiple regression models to test the interaction between the time-varying variates new-onset AKI or electrolyte or acid-base disorders and Sequential Organ Failure Assessment (SOFA) or Acute Physiology and Chronic Health Evaluation II (APACHE II) score at admission. After adjusting for age, sex, Charlson's comorbidity index, and AKI present at ICU admission, new-onset AKI was significantly associated with 28-day mortality only in the patients in the lowest and middle SOFA score tertiles [lowest SOFA tertile, hazard ratio (HR) 4.27 (95% CI: 1.27-14.44; P = 0.019), middle SOFA tertile, HR 3.17 (95% CI: 1.11-9.04, P = 0.031), highest SOFA tertile, HR 0.77 (95% CI: 0.24-2.50; P = 0.66); P = 0.026 for interaction with SOFA as a continuous variable]. After stratifying for APACHE II tertile, results were similar [adjusted HR (aHR) in the lowest tertile 6.24 (95% CI: 1.85-21.03, P = 0.003)]. SOFA or APACHE II at admission did not affect the relationship of serum electrolytes and acid-base status with mortality, except for new-onset acidosis which was associated with increased mortality, with the HR of death increasing with SOFA or APACHE II score (P < 0.001 and P = 0.013, respectively). Thus, unlike in the most severe critically ill patients admitted to the ICU for COVID-19, in patients with the less severe conditions at admission the development of AKI during the stay is a strong indicator of increased hazard of death.

Low skeletal muscle mass by computerized tomography is associated with increased mortality risk in end-stage kidney disease patients on hemodialysis.

BACKGROUND AND AIMS: Skeletal muscle (SM) area, as measured by abdominal CT at the level of the third lumbar vertebra (L3), has been proposed as a proxy of whole body muscle mass. However, population-specific reference values are lacking. In the present study we aimed at: (1) detecting low SM area on abdominal CT images in patients on hemodialysis by applying cut-offs derived from a group of healthy subjects, and (2) estimating the independent risk of all-cause mortality associated with low SM area. METHODS: We retrospectively enrolled 212 adult patients on hemodialysis, undergoing abdominal CT scan (study group), and 87 healthy kidney donors (reference group). We obtained the gender-specific 5th percentile values of the abdominal SM area distribution from both the whole control group and the subgroup of younger (29-60 years) subjects, which we used as reference cut-offs. Then we applied those cut-offs in the study group to identify patients with low SM area. We used survival and Cox regression analysis to evaluate the risk of all-cause mortality associated with low abdominal SM area. RESULTS: In the fully adjusted Cox regression analysis, the patients with low abdominal SM area had a higher risk of death than the patients with values above the reference cut-off derived in the subgroup of younger controls (adjHR = 1.79 (1.21; 2.67), P = 0.004). CONCLUSIONS: Abdominal CT imaging can be used to detect low abdominal SM area in patients on hemodialysis by applying cut-offs derived from healthy subjects sharing a similar ethnic background. Low SM area as assessed by CT is independently associated with all-cause mortality in ESKD patients on hemodialysis.

Acute kidney injury referred to the nephrologist: A single centre experience in a tertiary care hospital.

AIM: Acute kidney injury (AKI) shows an increasing incidence, accounting for a remarkable proportion of nephrology team in-hospital activity. The aim was to describe main features and outcomes of AKI observed in patients admitted to a tertiary care hospital. METHODS: We conducted a retrospective analysis in all consecutive AKI patients referred for nephrology consultation (November 2018-February 2020) focusing on the factors associated with in-hospital mortality within 90 days and kidney function recovery (KFR) upon discharge. Demographic, clinical and laboratory data, as well as main features of AKI episodes, were collected from medical records of the entire hospital stay. AKI was defined according to KDIGO Clinical Practice Guideline. RESULTS: Among 1145 patients referred for nephrology consultation, 559 were evaluated for AKI (598 episodes). Pre-existing CKD was present in 54.7% of patients. In 69.2% of cases AKI was evaluated within 48 h from its onset. Most of the episodes (66.6%) were classified as KDIGO Stage 3. In-hospital mortality within 90 days since admission was 43.3%. Multivariate Cox regression analysis showed a higher mortality risk for advancing age (HR 1.02/unit, 95% CI 1.01-1.03) and oliguria (HR 1.91, 95% CI 1.45-2.52), while a higher eGFR (HR 0.72/unit, 95% CI 0.54-0.95) and KFR within 7 days (HR 0.62, 95% CI 0.41-0.94) were associated to a lower mortality. KFR was observed in 96.4% of survivors. In patients with partial KFR, the loss of eGFR was -29.2 ± 17.9 ml/min. KFR incidence rate was 6.79 per 100-person days (95% CI 6.72-6.87) in survivors and 2.30 (95% CI 2.25-2.35) in non-survivors. CONCLUSION: AKI-related nephrology activity accounts for most of the nephrologist workload as consultant. Referred AKI episodes are frequently severe and superimposed on CKD, carrying a relatively high mortality in a patient population developing AKI outside ICU. Early KFR appears strongly associated with a favourable impact upon in-hospital survival.

Ultrasound for Non-invasive Assessment and Monitoring of Quadriceps Muscle Thickness in Critically Ill Patients With Acute Kidney Injury.

Background and aims: Critically ill patients with acute kidney injury (AKI) undergo major muscle wasting in the first few days of ICU stay. An important concern in this clinical setting is the lack of adequate tools for routine bedside evaluation of the skeletal muscle mass, both for the determination of nutritional status at admission, and for monitoring. In this regard, the present study aims to ascertain if ultrasound (US) is able to detect changes in quadriceps muscle thickness of critically ill patients with acute kidney injury (AKI) over short periods of time. Methods: This is a prospective observational study with a follow-up at 5 days. All adult patients with AKI hospitalized at the Renal ICU of the Parma University Hospital over 12 months, with a hospital stay before ICU admission no longer than 72 h, and with a planned ICU stay of at least 5 days, were eligible for the study. An experienced investigator assessed quadriceps rectus femoris and vastus intermedius thickness (QRFT and QVIT) at baseline and after 5 days of ICU stay. Results: We enrolled 30 patients with 74 ± 11 years of age and APACHE II score of 22 ± 5. Muscle thickness decreased by 15 ± 13% within the first 5 days of ICU stay (P < 0.001 for all sites as compared to ICU admission). Patients with more severe muscle loss had lower probability of being discharged home (OR: 0.04, 95%CI: 0.00-0.74; P = 0.031). Conclusions: In critically ill patients with AKI, bedside muscle US identifies patients with accelerated muscle wasting.

Sustained low-efficiency dialysis with regional citrate anticoagulation in critically ill patients with COVID-19 associated AKI: A pilot study.

Acute Kidney Injury (AKI) is a frequent complication in critically ill patients with Coronavirus disease 2019 (COVID-19), and it has been associated with worse clinical outcomes, especially when Kidney Replacement Therapy (KRT) is required. A condition of hypercoagulability has been frequently reported in COVID-19 patients, and this very fact may complicate KRT management. Sustained Low Efficiency Dialysis (SLED) is a hybrid dialysis modality increasingly used in critically ill patients since it allows to maintain acceptable hemodynamic stability and to overcome the increased clotting risk of the extracorporeal circuit, especially when Regional Citrate Anticoagulation (RCA) protocols are applied. Notably, given the mainly diffusive mechanism of solute transport, SLED is associated with lower stress on both hemofilter and blood cells as compared to convective KRT modalities. Finally, RCA, as compared with heparin-based protocols, does not further increase the already high hemorrhagic risk of patients with AKI. Based on these premises, we performed a pilot study on the clinical management of critically ill patients with COVID-19 associated AKI who underwent SLED with a simplified RCA protocol. Low circuit clotting rates were observed, as well as adequate KRT duration was achieved in most cases, without any relevant metabolic complication nor worsening of hemodynamic status.

Prevention of hypomagnesemia in critically ill patients with acute kidney injury on continuous kidney replacement therapy: the role of early supplementation and close monitoring.

Hypomagnesemia is a common electrolyte disorder in critically ill patients and is associated with increased morbidity and mortality risk. Many clinical conditions may contribute to hypomagnesemia through different pathogenetic mechanisms. In patients with acute kidney injury (AKI) the need for continuous or prolonged intermittent kidney replacement therapy (CKRT and PIKRT, respectively) may further add to other causes of hypomagnesemia, especially when regional citrate anticoagulation (RCA) is used. The basic principle of RCA is chelation of ionized calcium by citrate within the extracorporeal circuit, thus blocking the coagulation cascade. Magnesium, a divalent cation, follows the same fate as calcium; the amount lost in the effluent includes both magnesium-citrate complexes and the free fraction directly diffusing through the hemofilter. While increasing the magnesium content of dialysis/replacement solutions may decrease the risk of hypomagnesemia, the optimal concentration for the variable combination of solutions adopted in different KRT protocols has not yet been identified. An alternative and effective approach is based on including early intravenous magnesium supplementation in the KRT protocol, and close monitoring of serum magnesium levels, especially in the setting of RCA. Thus, strategies aimed at precisely tailoring both dialysis prescriptions and the composition of KRT fluids, as well as early magnesium supplementation and close monitoring, could represent a cornerstone in reducing KRT-related hypomagnesemia.

Muscle mass assessment in renal disease: the role of imaging techniques.

Muscle wasting is a frequent finding in patients with chronic kidney disease (CKD), especially in those with end-stage kidney disease (ESKD) on chronic dialysis. Muscle wasting in CKD is a main feature of malnutrition, and results principally from a vast array of metabolic derangements typical of the syndrome, that converge in determining reduced protein synthesis and accelerated protein catabolism. In this clinical setting, muscle wasting is also frequently associated with disability, frailty, infections, depression, worsened quality of life and increased mortality. On these grounds, the evaluation of nutritional status is crucial for an adequate management of renal patients, and consists of a comprehensive assessment allowing for the identification of malnourished patients and patients at nutritional risk. It is based essentially on the assessment of the extent and trend of body weight loss, as well as of spontaneous dietary intake. Another key component of this evaluation is the determination of body composition, which, depending on the selected method among several ones available, can identify accurately patients with decreased muscle mass. The choice will depend on the availability and ease of application of a specific technique in clinical practice based on local experience, staff resources and good repeatability over time. Surrogate methods, such as anthropometry and bioimpedance analysis (BIA), represent the most readily available techniques. Other methods based on imaging modalities [dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), and whole body computed tomography (CT)] are considered to be the "gold standard" reference methods for muscle mass evaluation, but their use is mainly confined to research purposes. New imaging modalities, such as segmental CT scan and muscle ultrasound have been proposed in recent years. Particularly, ultrasound is a promising technique in this field, as it is commonly available for bedside evaluation of renal patients in nephrology wards. However, more data are needed before a routine use of ultrasound for muscle mass evaluation can be recommended in clinical practice.

[Extracorporeal renal replacement therapies in lithium intoxication].

Drug poisoning is a significant source of morbidity, mortality and health care expenditure worldwide. Lithium, methanol, ethylene glycol and salicylates are the most important ones, included in the list of poisons, that may require extracorporeal depuration. Lithium is the cornerstone of treatment for bipolar disorders, but it has a narrow therapeutic window. The therapeutic range is 0.6-1.2 mEq/L and toxicity manifestations begin to appear as soon as serum levels exceed 1.5 mEq/L. Severe toxicity can be observed when plasma levels are more than 3.5 mEq/L. Lithium poisoning can be life threatening and extracorporeal renal replacement therapies can reverse toxic symptoms. Currently, conventional intermittent hemodialysis (IHD) is the preferred extracorporeal treatment modality. Preliminary data with prolonged intermittent renal replacement (PIRRT) therapies - hybrid forms of renal replacement therapy (RRT) such as sustained low efficiency dialysis (SLED) - seem to justify their role as potential alternative to conventional IHD. Indeed, SLED allows rapid and effective lithium removal with resolution of symptoms, also minimizing rebound phenomenon.

Validation by CT scan of quadriceps muscle thickness measurement by ultrasound in acute kidney injury.

BACKGROUND: Accelerated muscle wasting still represents a major issue in critically ill patients. However, a key problem in the intensive care unit is the lack of adequate tools for bedside evaluation of muscle mass. Moreover, when acute kidney injury (AKI) coexists, fluid overload and/or rapid fluid shifts due to renal replacement therapies that frequently occur and may interfere with muscle mass assessment. The purpose of this study is to validate muscle ultrasound (US) by a gold standard (muscle CT scan) for the assessment of quadriceps muscle thickness in critically ill patients with AKI. METHODS: Quadriceps rectus femoris thickness and quadriceps vastus intermedius thickness of critically ill patients with AKI were blindly assessed at the same leg sites by both US and computed tomography (CT) scan. Using bivariate mixed-model linear regression analysis, we estimated, average difference in thickness between measurement sites, agreement (differential and proportional bias) of US compared to CT, and precision of the two methods, and eventually performed Bland-Altman analysis for repeated measurements on pooled results. RESULTS: We analyzed 233 couples of measurements (30 patients). Average muscle thickness ranged between 1.0 and 1.6, depending on the measurement site. When comparing US to CT, both the observed differential bias (between + 0.04 and + 0.26 cm depending on the muscle site) and the proportional bias (between 82 and 98% of the reference values, depending on the muscle site) were not statistically significant. However, precision analysis showed that US scan tended to be slightly less precise in comparison to CT. Bland-Altman analysis on pooled results showed that the 95% limits of agreement between the US and CT were narrow, ranging from - 0.34 to + 0.36 cm. CONCLUSION: In critically ill patients with AKI, quadriceps muscle thickness assessment based on US is unbiased, although it occurs with a minor loss of precision compared to CT.