Refeeding syndrome in a Malaysian intensive care unit: an assessment of incidence, risk factors and outcome

Objective: Refeeding hypophosphataemia (RH) is characterised by acute electrolyte derangement following the start of nutrition. Complications associated with this syndrome include heart failure, respiratory failure, paraesthesia, seizure and death. We aim to assess its incidence, risk factors, and outcome in our local intensive care unit (ICU). Methods: This is a preliminary analysis prospective observational study at the ICU of Hospital Tengku Ampuan Afzan Kuantan. The study was registered under the National Medical Research Register (NMRR-14-803-19813) and has received ethical approval. Inclusion criteria includes adult admission longer than 48 hours who were started on enteral feeding in the ICU. Chronic renal failure patients and those receiving dialysis were excluded. RH was considered if plasma phosphate was less than 0.65 mmol/l within 7 days of ICU admission. Results: A total of 108 patients were recruited into the study. Of this, 51 (47.2%) had RH. Patients with RH had higher SOFA score compared to those without RH (7.1±3.0 vs 5.7±3.4, p=0.02). There were no differences in the APACHE II score (16±6 vs 15±6, p=0.30), and in the NUTRIC score (2.9±1.7 versus 2.7±1.7, p=0.63) between patients with and without RH. Patients with RH had lower albumin concentration compared to those without RH (23 vs 25, p=0.04). There were lower trend of magnesium, calcium and potassium concentration, however these were not statistically significant. All four patients with hypomagnesaemia (less than 0.5 mmol/l) had RH (p=0.04). There were no differences in mortality, length of hospital or ICU stay and duration of mechanical ventilation. Conclusion: Refeeding hypophosphataemia is common, occurring in almost half of ICU admission. Patients with RH had higher organ failure score, and lower albumin level. There were no differences in the NUTRIC score and in short-term outcomes. Further studies could evaluate the association between RH and long-term outcome

025 Estimates of glomerular filtration rate in the critically ill with sepsis

Accurate assessment of glomerular filtration rate (GFR) in ICU patients is very important for institution of supportive therapy, preventive therapy, early renal support, drug dosing modification or avoidance of nephrotoxic drugs. Kinetic estimate of GFR (keGFR) takes into account the changes of creatinine over time, creatinine production rate, and the volume of distribution, hence postulated to be a more accurate estimate of GFR in the acute setting, where there are rapidly changing kidney functions as in the critically ill. We evaluated the association of the keGFR with estimated GFR (eGFR) by conventional method

The utility of biomarker excretion rates in acute kidney injury

INTRODUCTION: The concentration of urinary biomarkers of acute kidney injury (AKI) is influenced by variation in urinary concentration within and between individuals.1 Normalisation to urine creatinine concentration is commonly used to account for this variation.2 The accuracy of this method is compromised by tubular secretion of creatinine, and variations in urine creatinine excretion in non-steady state when glomerular filtration rate (GFR) changes.1 Alternatives to normalisation to creatinine include using the absolute biomarker concentration or quantifying the biomarker excretion rate. Intuitively, the excretion rate may also account for variation in water reabsorption and urine flow rate. In addition, total biomarker excretion in AKI might more accurately reflect the mass of injured tubular cells, a function of both severity and duration, parameters associated with long-term mortality.3 OBJECTIVE: To compare the performance of biomarker excretion rate and the absolute and normalized biomarker concentration in diagnosis of AKI, prediction of AKI, death and the need for renal replacement therapy (RRT) in adult intensive care patients. This will assists in the comparison of biomarkers between trials and guide clinicians on how it should be utilized in clinical practice. METHODS: Urinary concentrations of alkaline phosphatase (AP), γ-glutamyl transpeptidase (GGT), cystatin C (CysC), neutrophil gelatinase-associated-lipocalin (NGAL), kidney-injury molecule-1 (KIM 1), and interleukin-18(IL-18) were measured on ICU admission, at 12 and 24 hours in the EARLYARF trial.4, 5 The average urine flow rate was calculated from 4-hour creatinine clearance measurements obtained at the same time points, which allowed calculation of biomarker excretion rate. The normalised biomarker concentrations were derived by dividing the biomarker concentration by the urinary creatinine concentration. The total excretion over 24 hours for each biomarker (i.e. integration of excretion rate with respect to time) was determined using the trapezoidal rule. The performance of absolute and normalised biomarker concentration, and biomarker excretion rate on admission to the ICU in diagnosis or prediction of outcome was assessed by comparison of the area under the curve (AUC) of receiver-operator characteristic curves (ROC) for each parameter using the DeLong method.6, 7 The association of total biomarker excretion with AKI severity (maximum AKIN stages within 48 hours), and 1-year survival were assessed with one-way ANOVA and Kaplan Meier survival analysis. RESULTS: Of 528 recruited patients, 484 had 4h-creatinine clearance measurements on ICU admission from which urine output volumes could be obtained for the calculation of biomarker excretion rates. For diagnosis of AKI on ICU admission, biomarker concentration performed better than normalised concentration or excretion rate. Normalised concentrations performed best in prediction of 7-day mortality and the need of RRT. Excretion rate did not diagnose or predict outcomes better than absolute or normalised concentration. In the cohort of patients without AKI on ICU admission (n=339), there were no differences in performance between absolute and normalised biomarker concentration in prediction of development of AKI within 48 hours (AKIN48) or sustained AKI within 7 days of admission (RIFLE 24). However, here also the normalised concentrations had higher AUCs than excretion rates (Figure 1). The total biomarker excretion in the first 24 hours increased with severity of injury for all biomarkers except AP. For NGAL alone, post-hoc analysis also demonstrated significant differences between successive AKIN stages of increasing severity AKI (p≤0.02) (Figure 2). Patient survival was assessed according to extent of biomarker excretion ranked by tertiles Only NGAL demonstrated a significant association between total excretion and survival over 365 days (log-rank test, p=0.04). After adjusting for age, gender, sepsis, APACHE II and SOFA scores, patients with higher excretion of NGAL (higher tertile, total excretion >184µg) had a higher 1-year mortality compared to those with a lower tertile of NGAL excretion (total excretion of <40µg) (Hazard ratio of 2.15 (95% CI: 1.23 to 3.73), p=0.007) (Figure 3). . CONCLUSIONS: Normalisation to urine creatinine provides no advantage in diagnosis of AKI, but improves prediction of AKI and outcome. Periodic excretion rates did not improve performance, but total excretion in the first 24hr was strongly associated with AKI severity, and for NGAL with survival. The ideal method for standardizing urinary AKI biomarkers depends on the outcome being assessed

Urine output in diagnosing acute kidney injury and predicting mortality

Background: Urine output is the oldest biomarker of AKI. Clinically it can be the first indication of kidney dysfunction, especially in critical care settings where hourly urine outputs are routinely measured. It has been shown that the ideal urine output threshold for prediction of mortality or dialysis was 0.3 ml/kg/h for moving block of 6 hours. Objectives: We aim to assess this threshold in mortality prediction in our ICU population. Methods: This was a secondary analysis of a single centre, prospective observational study. Admission of less than 48 hours, post-elective surgery and ICU readmission were excluded. A moving average urine output over 6 hours over body weight was calculated for the first 48th hour post ICU admission. AKIuo was defined if urine output less than 0.5 ml/kg/h, and UO0.3 less than 0.3 ml/kg/h. Results: A total of 143 patients were recruited, of these 87 (61%) had AKIuo, and 52 (36%) had UO0.3. The AUC of AKIuo in predicting mortality was 0.62 (0.51 to 0.72), and UO0.3 was 0.66 (0.55 to 0.77). There were lower survival in patients with AKIuo and UO0.3 compared to those without (p=0.01, and 0.001, respectively). However, after adjusting for covariates (age and SOFA score without renal score), only UO0.3 but not AKIuo independently predicted mortality (HR 2.44 (1.15 to 5.18)). AKUuo assessed over 6 hours or longer independently predicted mortality, whereas UO0.3 assessed over 2 hours or longer predicted mortality. Conclusions: A threshold of 6 hourly urine output of 0.3 ml/kg/h but not 0.5 ml/kg/h was independently predictive of mortality. Duration of urine output assessed as low as 2 hours can be used when utilisng the stricker definiton, whereas at 6 hours is needed using the standard criteria. This support previous finding of a more stricker urine output definition in acute kidney injury

Validating a lower urine output criteria in predicting death in critically ill patients

Introduction: Urine output provides a rapid estimate for kidney function, and its use has been incorporated in the diagnosis of acute kidney injury. However, not many studies had validated its use compared to the plasma creatinine. It has been showed that the ideal urine output threshold for prediction of death or the need for dialysis was 0.3 ml/kg/h. We aim to assess this threshold in our local ICU population. Materials and Methods: This was a secondary analysis of an observational study done in critically ill patients. Hourly urine output data was collected, and a moving average of 6-hourly urine output was calculated over the first 48 hours of ICU admission. AKIuo was defined if urine output ≤ 0.5 ml/kg/h, and UO0.3 was defined as urine output ≤ 0.3 ml/kg/h. Results: 143 patients were recruited into the study, of these, 87 (61%) had AKIuo, and 52 (36%) had UO0.3. The AUC of AKIuo in predicting death was 0.62 (0.51 to 0.72), and UO0.3 was 0.66 (0.55 to 0.77). There was lower survival in patients with AKIuo and UO0.3 compared to those without (p=0.01, and 0.001, respectively). However, only UO0.3 but not AKIuo independently predicted death (HR 2.44 (1.15 to 5.18)). Conclusions: A threshold of 6 hourly urine output of 0.3 ml/kg/h but not 0.5 ml/kg/h independently predictive of death. This support previous finding of a lower threshold of urine output criteria for optimal prediction

Derivation of a new bioscore for predicting mortality in sepsis

Introduction: Currently, there is a lack of clinically feasible and reliable method for discriminating outcome in sepsis. We aimed to derive a new bioscore for predicting mortality in critically ill patients with sepsis using a combination of biomarkers and clinical indexes. Materials and Methods: This was a secondary analysis from a prospective study involving 159 patients with sepsis admitted to an intensive care unit (ICU). Data for key variables considered for possible inclusion in the score were collected, which included: age, sex, source of admission, comorbidities, microorganism, bacteraemia, site of infection, septic shock status, baseline Simplified Acute Physiological Score II, Sequential Organ Failure Assessment (SOFA) score (total and organ sub-scores), C-reactive protein, procalcitonin and interleukin-6 (IL-6). Approximate quintiles of each variable were given points as per the strength of their association with 30-day mortality. Results: In accordance with the statistical significance in the logistic regression analysis, the final score utilised candidate variables of age, central nervous system and liver SOFA sub-scores and IL-6. The bioscore predicted 30-day mortality with a very good performance [area under the receiver operating characteristic curve 0.814 (95% confidence interval 0.745-0.871, p <0.0001)] in our sepsis cohort. A bioscore greater than 4 predicted 30-day mortality with 80.4% sensitivity, 69.9% specificity, 2.67 positive likelihood ratio and 0.28 negative likelihood ratio. As the score increased, so did mortality rate. Conclusion: A new bioscore combining age, central nervous system and liver SOFA sub-scores and IL-6 measured on ICU admission potentially improves prediction of mortality in sepsis. Further study is warranted to prospectively validate the clinical utility of this bioscore in risk-stratifying patients with suspected sepsis

Refeeding hypophosphataemia after enteral nutrition in a Malaysian intensive care unit: risk factors and outcome

Background and Objectives: Refeeding hypophosphataemia (RH) is characterized by an acute electrolyte derangement following nutrition therapy. Complications associated include heart failure, respiratory failure, paraesthesia, seizure and death. We aim to assess its incidence, risk factors, and outcome in our local intensive care unit (ICU). Methods and Study Designs: A prospective observational cohort study was conducted at the mixed medical-surgical of a tertiary ICU in Kuantan, Malaysia. The study was registered under the National Medical Research Register (NMRR-14-803-19813) and has received ethical approval. Inclusion criteria include adult admission longer than 48 hours who were started on enteral feeding. Chronic renal failure patients and those receiving dialysis were excluded. RH was defined as plasma phosphate less than 0.65 mmol/L and a drop of more than 0.16 mmol/L following feeding. Results: A total of 109 patients were recruited, of which 44 (42.6%) had RH. Patients with RH had higher SOFA score compared to those without (p=0.04). There were no differences in the APACHE II and NUTRIC scores. Serum albumin was lower in those with RH (p=0.04). After refeeding, patients with RH had lower serum phosphate, magnesium and albumin, and higher supplementation of phosphate, potassium and calcium. There were no differences in mortality, length of hospital or ICU stay. Conclusions: Refeeding hypophosphataemia occurs in almost half of ICU admission. Risk factors for refeeding include high organ failure score and low albumin. Refeeding was associated with imbalances in phosphate, magnesium, potassium and calcium. Future larger study may further investigate these risk factors and long-term outcomes

The impact of fluid balances in the first 48 hours on mortality in the critically ill patients

Introduction: There has been increasing evidence of detrimental effects of cumulative positive fluid balance in critically ill patients. The postulated mechanism of harm is the development of interstitial oedema, with resultant increase morbidity and mortality. We aim to assess the impact of positive fluid balance within the first 48 hours on mortality in our local ICU population. Methods: This was a secondary analysis of a single centre, prospective observational study. All ICU patients more than 18 years were screened for inclusion in the study. Admission of less than 48 hours, post-elective surgery and ICU readmission were excluded. Cumulative fluid balance either as volume or percentage of body weight from admission was calculated over 6, 24 and 48 hour period from ICU admission. Results: A total of 143 patients were recruited, of these 33 died. There were higher cumulative fluid balances at 6, 24 and 48 hours in non- survivors compared to survivors. However, after adjusted for severity of illness, APACHE II Score, they were not predictive of mortality. Sensitivity analysis on sub-cohort of patients with acute kidney injury (AKI) showed only an actual 48-hour cumulative fluid balance was independently predictive of mortality (1.21 (1.03 to 1.42)). Conclusions: Cumulative fluid balance was not independently predictive of mortality in a heterogenous group of critically ill patients. However, in subcohort of patients with AKI, a 48-hour cumulative fluid balance was independently predictive of mortality. An additional tile is thus added to the mosaic of findings on the impact of fluid balance in a hetergenous group of critically ill patients, and in sub- cohort of AKI patients

Sepsis mortality score for the prediction of mortality in septic patients

Purpose: To derive a prediction equation for 30-day mortality in sepsis using a multi-marker approach and compare its performance to the Sequential Organ Failure Assessment (SOFA) score. Methods: This study included 159 septic patients admitted to an intensive care unit. Leukocytes count, procalcitonin (PCT), interleukin-6 (IL-6), and paraoxonase (PON) and arylesterase (ARE) activities of PON-1 were assayed from blood obtained on ICU presentation. Logistic regression was used to derive sepsis mortality score (SMS), a prediction equation describing the relationship between biomarkers and 30-day mortality. Results: The 30-day mortality rate was 28.9%. The SMS was [еlogit(p)/(1 + еlogit(p))] × 100; logit(p) =0.74+ (0.004 × PCT)+(0.001 × IL-6)−(0.025 × ARE)−(0.059 × leukocytes count). The SMC had higher area under the receiver operating characteristic curve (95% Cl) than SOFA score [0.814 (0.736–0.892) vs. 0.767 (0.677–0.857)], but is not statistically significant.When the SMSwas added to the SOFA score, prediction of 30-day mortality improved compared to SOFA score used alone [0.845 (0.777–0.899), p=0.022]. Conclusions: A sepsismortality score using baseline leukocytes count, PCT, IL-6 and ARE was derived, which predicted 30-day mortality with very good performance and added significant prognostic information to SOFA score

Validation of the 28-day mortality prognostic performance of the modified nutrition risk in critically ill score in a Malaysian intensive care unit

Introduction: The mNUTRIC score is a nutritional assessment tool to identify critically ill patients with high nutritional risk who could benefit from nutritional interventions. This study was conducted to validate the 28-day mortality prognostic performance of the mNUTRIC score in a Malaysian intensive care unit (ICU). Methods: This was a retrospective cohort study of adult patients who were consecutively admitted to the ICU from January 2017 to December 2018 for >24 hours. Data were collected on variables required to calculate the mNUTRIC score. Patients with mNUTRIC score ≥5 points were considered to be at high nutritional risk. Main outcome was 28- day mortality from all causes; ICU length of stay (LOS) and prolonged mechanical ventilation (MV) (>2 days) were secondary outcomes. Results: From a total of 432 admissions, 382 (88.4%) patients fulfilled the study criteria. Seventy-seven (20.2%) of these patients were at high nutritional risk. They had longer mean ICU LOS (7.1±7.5 days versus 4.2±4.0 days, p=0.001), greater proportion of prolonged MV (57.1% versus 14.4%, p<0.001) and higher 28-day mortality (44.2% versus 10.2%, p<0.001) compared to patients with low mNUTRIC score (≤4 points). High mNUTRIC score predicted 28-day mortality with area under the curve (AUC) of 0.797 (95% confidence interval: 0.738-0.856). Conclusion: High mNUTRIC score was associated with a higher 28-day mortality. The prognostic performance for 28-day mortality of the mNUTRIC score is clinically valid as indicated by AUC >0.7 and is comparable to the results of other validation studies. In addition, patients with high mNUTRIC score had increased ICU LOS and prolonged MV. Key words: Nutritional status, critically ill, mortalit