4.  Brief description of the proposal –

Background and Brief review of literature:

Justification for study: To observe the changes in serum sodium that can happen in critically ill patients subjected to slow low efficiency dialysis (SLED), with pre-existing with abnormal serum sodium (Na) values (dysnatremia) before  SLED and evaluate their mortality. 

Methodology describing the potential risks & benefits and outcome measures:  

Prospective cohort study

Adult patients (age>18 years) with acute kidney injury (AKI) or acute on chronic kidney disease (CKD) who will be undergoing renal replacement therapy (RRT) as decided by the physician will be included in the study after obtaining the consent. Patient demographics (age, sex, ideal body weight, co-morbidities) and clinical data (hemodynamic and ventilatory support, severity illness scores like SOFA, APACHE II) will be noted. Once decisioned to receive SLED was made by the treating physician, a vascular access via right femoral (13 Fr/15 cm) or right internal jugular (13 Fr/ 15 cm) double lumen haemodialysis catheter will be inserted in all the patients. The standard haemodialysis prescription for SLED by institute protocol includes duration of 8-12 hours, use of 35ºC-37 ºC dialysate, ultrafiltration (UF) of 100-200ml/hour, blood flow rate of 150 -250 ml/minute and dialysate flow rate 200-300 ml/minute. The dialysate composition with regard to dialysate potassium (2 mEq/L), calcium (3.5 mEq/L) and bicarbonate (32 mEq/L) will be kept constant to all the study participants. All the dialysis sessions will be performed on Fresenius 5008 S with FX60 dialyzers made of polysulfone with surface area of 1.3 m² and ultrafiltration co-efficient (K_UF) of 13 ml/min/mm Hg.

The patients pre-dialysis sodium will be noted five minutes before the onset of SLED along with the dialysate sodium set by the physician on the machine followed by post dialysis sodium five minutes after the termination of SLED. The difference between Pre and post (Pre-post Na) and Pre and set dialysate (Pre-set Na) will be noted down. All the sodium measurements will be done through laboratory using ion selective electrodes in well calibrated machines. Online Kt/V displayed on the machine will be noted at the start and the end of RRT. All the diagnostic tests are done as part of patient management in the ICU.

The patient outcome (30 day mortality) will be assessed in different aspects:

1. Δ Pre-post dialysis Na difference
2. Severity of dysnatremia at the onset of SLED and its relation to mortality –

Mild hyponatremia :130-135 mmol/L

Moderate hyponatremia: 125-129 mmol/L

Severe hyponatremia:<125 mmol/L

Mild hypernatremia :145–150 mmol/L

Moderate hypernatremia (151–160 mmol/L)

Severe hypernatremia: >160 mmol/L

3. Pre and set dialysate (Pre-set Na) difference on SLED and mortality
4. Further analysis based on change in Na: Δ Pre-post  SLED Na difference  and their association with mortality

Change in Na <10 mmol/L:

Change in Na >10 mmol/L:

Aim(s) & objectives :

Primary Objective: 30 day all cause mortality after starting SLED in patients with dysnatremia

Secondary Objective:

To correlate the change in Na (Pre-post) dialysis to 30 day mortality

To correlate the severity of dysnatremia with 30 day mortality

Factors associated with 30 day mortality  

Inclusion criteria:

1.Patients with age > 18 years with acute kidney injury (AKI) stage 2 and 3 as defined by KDIGO or Acute on Chronic Kidney disease for whom SLED was prescribed  by the treating physician 

2. Serum Na less than 135 mmol/L OR more than 145 mmol/L will be screened to be included in the study.

3. Patients with dysnatremia who undergo one session of SLED will be included only once in the study  

Exclusion criteria :

1.     The patients whose pre dialysis Na is between 135-145 mmol/L

2.     The patients who could not complete the SLED session scheduled for 8-10 hours

3.     Patients who were end stage renal disease and received dialysis before enrolment

Sample size & Statistical analysis: For the calculation of sample size, proportion of 30-day mortality was assumed as 57.5% [10], relative precision as 20%, alpha error as 5%, and beta error as 20%. Final sample size came out to be 98 which was rounded off to 100.

Categorical variables will be presented as proportions or percentages. Continuous variables will be presented as mean (SD) or median (IQR) as appropriate. Normality of data will be assessed using Shapiro-Wilk test. Difference in proportions between two or more groups will be compared using Chi-square test. To compare means between two groups, t-test will be used and to compare medians, Mann-Whitney U test will be used. To identify the independent predictors of cardiac output, linear regression will be done. Survival curves will be drawn by Kaplan-Meir method and to compare survival curves between groups, the log-rank test will be done. Odds ratio and 95% confidence interval (CIs) for 30 day mortality will be calculated based on logistic regression method. p-value of less than 0.05 will be considered as significant.

Refereneces:

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[2]      Güçyetmez B, Ayyildiz AC, Ogan A, Guder BY, ÖzçobanoÄŸlu S, Ayyildiz A, et al. Dysnatremia on intensive care unit admission is a stronger risk factor when associated with organ dysfunction. Minerva Anestesiol 2014;80:1096–104.

[3]      Lindner G. Dysnatremias in the ICU: prospective intervention studies needed. Minerva Anestesiol 2014;80:1074–5.

[4]      Darmon M, Diconne E, Souweine B, Ruckly S, Adrie C, Azoulay E, et al. Prognostic consequences of borderline dysnatremia: pay attention to minimal serum sodium change. Crit Care 2013;17:R12. https://doi.org/10.1186/cc11937.

[5]      Sundar S, Korula S, Balakrishnan S, Paul V, Balagopal A. Acute kidney injury-incidence, prognostic factors, and outcome of patients in an Intensive Care Unit in a tertiary center: A prospective observational study. Indian J Crit Care Med 2016;20:332–6. https://doi.org/10.4103/0972-5229.183904.

[6]      Katsiampoura A, Toumpanakis D, Konsta K, Varkaris A, Vassilakopoulos T. Prediction of dysnatremias in critically ill patients based on the law of conservation of mass. Comparison of existing formulae. PLoS One 2018;13:e0207603. https://doi.org/10.1371/journal.pone.0207603.

[7]      Claure R, Bouchard J. Acid-Base and Electrolyte Abnormalities during Renal Support for Acute Kidney Injury: Recognition and Management. Blood Purif 2012;34:186–93. https://doi.org/10.1159/000341723.

[8]      Hwang KS, Choi EY, Park J-S, Lee CH, Kang CM, Kim G-H. Postdialysis serum sodium changes and systolic blood pressure in patients undergoing online hemodiafiltration and high-flux hemodialysis. Kidney Res Clin Pract 2013;32:62–5. https://doi.org/10.1016/j.krcp.2013.04.007.

[9]      Douvris A, Malhi G, Hiremath S, McIntyre L, Silver SA, Bagshaw SM, et al. Interventions to prevent hemodynamic instability during renal replacement therapy in critically ill patients: a systematic review. Crit Care 2018;22:41. https://doi.org/10.1186/s13054-018-1965-5.

[10]    Han SS, Bae E, Kim DK, Kim YS, Han JS, Joo KW. Dysnatremia, its correction, and mortality in patients undergoing continuous renal replacement therapy: a prospective observational study. BMC Nephrol 2016;17:2. https://doi.org/10.1186/s12882-015-0215-1.