Sepsis and Its Impact on Outcomes in Elderly Patients Admitted to a Malaysian Intensive Care Unit.

Sepsis is an important cause of morbidity and mortality in elderly patients, but there is a scarcity of data on sepsis in this specific cohort. We performed this study to review the impact of sepsis on outcomes in elderly patients admitted to our local intensive care unit (ICU). This was a secondary analysis of prospectively collected data of 159 consecutive adult patients with sepsis admitted to an ICU of a tertiary hospital in Malaysia over a three-year period. Of the 159 patients analysed, elderly patients constituted 18.9% of the cohort. Fifty percent of the older patients died within 30 days, compared to 24% of younger patients (P = 0.005). On multivariate analysis, old age was found to be independently predictive of 30-day mortality with an adjusted odds ratio (OR) of 2.5 (95% confidence interval [CI]: 1.05, 6.01) compared to younger patients (P = 0.021). In a Kaplan-Meier analysis, survival probability was significantly lower in patients of an older age compared to younger patients (P = 0.015). In conclusion, mortality from sepsis is considerably higher in elderly patients, with age as an independent risk factor for mortality.

Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.

RATIONALE & OBJECTIVE: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction. STUDY DESIGN: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines. SETTING & STUDY POPULATIONS: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms. SELECTION CRITERIA FOR STUDIES: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI. DATA EXTRACTION: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis. ANALYTICAL APPROACH: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses. RESULTS: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively. LIMITATIONS: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies. CONCLUSIONS: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.

Acute Kidney Injury in Malaysian Intensive Care Setting: Incidences, Risk Factors, and Outcome.

INTRODUCTION: Acute kidney injury (AKI) is common in the intensive care unit (ICU) with a high risk of morbidity and mortality. The high incidence of AKI in our population may be attributed to sepsis. We investigated the incidence, risk factors, and outcome of AKI in four tertiary Malaysian ICUs. We also evaluated its association with sepsis. MATERIALS AND METHODS: This retrospective cohort study extracted de-identified data from the Malaysian Registry of Intensive Care in four Malaysian tertiary ICUs between January 2010 and December 2014. The study was registered under the NMRR and approved by the ethics committee. AKI was defined as twice the baseline creatinine or urine output <0.5 ml/kg/h for 12 h. RESULTS: Of 26,663 patients, 24.2% had AKI within 24 h of admission. Patients with AKI were older and had higher severity of illness compared to those without AKI. AKI patients had a longer duration of mechanical ventilation, length of ICU, and hospital stay. Age, Simplified Acute Physiological II Score, and the presence of sepsis and preexisting hypertension, chronic cardiovascular disease independently associated with AKI. About 32.3% had sepsis. Patients with both AKI and sepsis had the highest risk of mortality (relative risk 3.43 [3.34-3.53]). CONCLUSIONS: AKI is common in our ICU, with higher morbidity and mortality. Independent risk factors of AKI include age, the severity of illness, sepsis and preexisting hypertension, and chronic cardiovascular disease. AKI independently contributes to mortality. The presence of AKI and sepsis increased the risk of mortality by three times.

Levels and Diagnostic Value of Model-based Insulin Sensitivity in Sepsis: A Preliminary Study.

BACKGROUND AND AIMS: Currently, there is a lack of real-time metric with high sensitivity and specificity to diagnose sepsis. Insulin sensitivity (SI) may be determined in real-time using mathematical glucose-insulin models; however, its effectiveness as a diagnostic test of sepsis is unknown. Our aims were to determine the levels and diagnostic value of model-based SI for identification of sepsis in critically ill patients. MATERIALS AND METHODS: In this retrospective, cohort study, we analyzed SI levels in septic (n = 18) and nonseptic (n = 20) patients at 1 (baseline), 4, 8, 12, 16, 20, and 24 h of their Intensive Care Unit admission. Patients with diabetes mellitus Type I or Type II were excluded from the study. The SI levels were derived by fitting the blood glucose levels, insulin infusion and glucose input rates into the Intensive Control of Insulin-Nutrition-Glucose model. RESULTS: The median SI levels were significantly lower in the sepsis than in the nonsepsis at all follow-up time points. The areas under the receiver operating characteristic curve of the model-based SI at baseline for discriminating sepsis from nonsepsis was 0.814 (95% confidence interval, 0.675-0.953). The optimal cutoff point of the SI test was 1.573 × 10-4 L/mu/min. At this cutoff point, the sensitivity was 77.8%, specificity was 75%, positive predictive value was 73.7%, and negative predictive value was 78.9%. CONCLUSIONS: Model-based SI ruled in and ruled out sepsis with fairly high sensitivity and specificity in our critically ill nondiabetic patients. These findings can be used as a foundation for further, prospective investigation in this area.

Plasma Neutrophil Gelatinase-Associated Lipocalin diagnosed acute kidney injury in patients with systemic inflammatory disease and sepsis.

AIM: Sepsis is the leading cause of intensive care unit (ICU) admission. Plasma Neutrophil Gelatinase Associated-Lipocalin (NGAL) is a promising biomarker for acute kidney injury (AKI) detection; however, it is also increased with inflammation and few studies have been conducted in non-Caucasian populations and/or in developing economies. Therefore, we evaluated plasma NGAL's diagnostic performance in the presence of sepsis and systemic inflammatory response syndrome (SIRS) in a Malaysian ICU cohort. METHODS: This is a prospective observational study on patients with SIRS. Plasma creatinine (pCr) and NGAL were measured on ICU admission. Patients were classified according to the occurrence of AKI and sepsis. RESULTS: Of 225 patients recruited, 129 (57%) had sepsis of whom 67 (52%) also had AKI. 96 patients (43%) had non-infectious SIRS, of whom 20 (21%) also had AKI. NGAL concentrations were higher in AKI patients within both the sepsis and non-infectious SIRS cohorts (both P < 0.0001). The diagnostic area under curve for AKI was 0.81 (95%CI: 0.74 to 0.87). The optimal cut-off was higher in sepsis compared to non-infectious SIRS patients (454 versus 176 ng/mL). Addition of NGAL to a clinical model comprising age, pCr, medical admission category and SAPS II score increased the mean risk of those with AKI by 4% and reduced the mean risk of those without AKI by 3%. CONCLUSIONS: Acute kidney injury is more common with sepsis than non-infectious SIRS. Plasma NGAL was diagnostic of AKI in both subgroups. The optimal cut-off for diagnosing AKI was higher in sepsis than in non-infectious SIRS. Addition of plasma NGAL improved the clinical model used to diagnose AKI.

Dynamic Changes of Plasma Neutrophil Gelatinase-Associated Lipocalin Predicted Mortality in Critically Ill Patients with Systemic Inflammatory Response Syndrome.

BACKGROUND AND AIMS: About 50% of patients admitted to the Intensive Care Unit have systemic inflammatory response syndrome (SIRS), and about 10%-20% of them died. Early risk stratification is important to reduce mortality. Plasma neutrophil gelatinase-associated lipocalin (NGAL) is increased by inflammation and infection. Its ability to predict mortality in SIRS patients is of interest. We evaluated the ability of serial measurement of NGAL for the prediction of mortality in critically ill patients with SIRS. MATERIALS AND METHODS: This is a secondary analysis of a single-center, prospective, observational study. Patients who fulfill the SIRS criteria were recruited in the study. Delta NGAL at 24 and 48 h (ΔNGAL-24 and ΔNGAL-48) was defined as 24 and 48 h NGAL minus day 1 NGAL; NGAL clearance (NGALc) was defined as percentage of ΔNGAL over day 1 NGAL. The primary outcome of the study is in-hospital mortality. RESULTS: A total of 151 patients were analyzed, of which 53 (35%) died. Nonsurvivors were older (51 vs. 45, P = 0.03) and had higher Sequential Organ Failure Assessment (9 ± 7 vs. 7 ± 4, P = 0.02) and Simplified Acute Physiology Score II (47 ± 15 vs. 40 ± 15, P = 0.01) scores as compared to survivors. NGAL concentrations over 3 days were higher in nonsurvivors compared to survivors (repeated measures analysis of variance, P = 0.02). Day 1 NGAL, ΔNGAL-24, and NGALc-24 were not independently predictive of mortality. However, day 3 NGAL, ΔNGAL-48, and NGALc-48 were predictive after adjusted for age and severity of illness (odds ratio 9.1 [1.97-41.7]). CONCLUSIONS: NGAL dynamics over 48 h independently predicted mortality in critically ill patients with SIRS. This could assist clinicians in risk stratification of this group of high-risk patients.

High frequency oscillatory ventilation in leptospirosis pulmonary hemorrhage syndrome: A case series study.

Hypoxemia in severe leptospirosis-associated pulmonary hemorrhage syndrome (LPHS) is a challenging clinical scenario not usually responsive to maximal support on mechanical ventilation. We described the efficacy and safety of high frequency oscillatory ventilation (HFOV) as rescue therapy in acute respiratory failure secondary to LPHS. This is a retrospective case study of five patients with diagnosis of severe LPHS, who were admitted to Intensive Care Unit from October 2014 to January 2015. They developed refractory hypoxemia on conventional mechanical ventilation and rescue therapy was indicated. All patients responded rapidly by showing improvements in oxygen index and PaO2/FiO2 ratio within first 72 h of therapy. Despite severity of illness evidenced by high Simplified Acute Physiological II and Sequential Organ Failure Assessment scores, all patients were discharged from hospital alive. In view of the rapid onset and extent of hemorrhage which may culminate quickly into asphyxiation and death, HFOV may indeed be lifesaving in severe LPHS.

The clinical utility window for acute kidney injury biomarkers in the critically ill.

INTRODUCTION: Acute Kidney Injury (AKI) biomarker utility depends on sample timing after the onset of renal injury. We compared biomarker performance on arrival in the emergency department (ED) with subsequent performance in the intensive care unit (ICU). METHODS: Urinary and plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL), and urinary Cystatin C (CysC), alkaline phosphatase, γ-Glutamyl Transpeptidase (GGT), α- and π-Glutathione S-Transferase (GST), and albumin were measured on ED presentation, and at 0, 4, 8, and 16 hours, and days 2, 4 and 7 in the ICU in patients after cardiac arrest, sustained or profound hypotension or ruptured abdominal aortic aneurysm. AKI was defined as plasma creatinine increase ≥ 26.5 µmol/l within 48 hours or ≥ 50% within 7 days. RESULTS: In total, 45 of 77 patients developed AKI. Most AKI patients had elevated urinary NGAL, and plasma NGAL and CysC in the period 6 to 24 hours post presentation. Biomarker performance in the ICU was similar or better than when measured earlier in the ED. Plasma NGAL diagnosed AKI at all sampling times, urinary NGAL, plasma and urinary CysC up to 48 hours, GGT 4 to 12 hours, and π-GST 8 to 12 hours post insult. Thirty-one patients died or required dialysis. Peak 24-hour urinary NGAL and albumin independently predicted 30-day mortality and dialysis; odds ratios 2.87 (1.32 to 6.26), and 2.72 (1.14 to 6.48), respectively. Urinary NGAL improved risk prediction by 11% (IDI event of 0.06 (0.002 to 0.19) and IDI non-event of 0.04 (0.002 to 0.12)). CONCLUSION: Early measurement in the ED has utility, but not better AKI diagnostic performance than later ICU measurement. Plasma NGAL diagnosed AKI at all time points. Urinary NGAL best predicted mortality or dialysis compared to other biomarkers. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12610001012066. Registered 12 February 2010.

Combining creatinine and volume kinetics identifies missed cases of acute kidney injury following cardiac arrest.

INTRODUCTION: Fluid resuscitation in the critically ill often results in a positive fluid balance, potentially diluting the serum creatinine concentration and delaying diagnosis of acute kidney injury (AKI). METHODS: Dilution during AKI was quantified by combining creatinine and volume kinetics to account for fluid type, and rates of fluid infusion and urine output. The model was refined using simulated patients receiving crystalloids or colloids under four glomerular filtration rate (GFR) change scenarios and then applied to a cohort of critically ill patients following cardiac arrest. RESULTS: The creatinine concentration decreased during six hours of fluid infusion at 1 litre-per-hour in simulated patients, irrespective of fluid type or extent of change in GFR (from 0% to 67% reduction). This delayed diagnosis of AKI by 2 to 9 hours. Crystalloids reduced creatinine concentration by 11 to 19% whereas colloids reduced concentration by 36 to 43%. The greatest reduction was at the end of the infusion period. Fluid dilution alone could not explain the rapid reduction of plasma creatinine concentration observed in 39 of 49 patients after cardiac arrest. Additional loss of creatinine production could account for those changes. AKI was suggested in six patients demonstrating little change in creatinine, since a 52 ± 13% reduction in GFR was required after accounting for fluid dilution and reduced creatinine production. Increased injury biomarkers within a few hours of cardiac arrest, including urinary cystatin C and plasma and urinary Neutrophil-Gelatinase-Associated-Lipocalin (biomarker-positive, creatinine-negative patients) also indicated AKI in these patients. CONCLUSIONS: Creatinine and volume kinetics combined to quantify GFR loss, even in the absence of an increase in creatinine. The model improved disease severity estimation, and demonstrated that diagnostic delays due to dilution are minimally affected by fluid type. Creatinine sampling should be delayed at least one hour following a large fluid bolus to avoid dilution. Unchanged plasma creatinine post cardiac arrest signifies renal injury and loss of function. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12610001012066.

The urine output definition of acute kidney injury is too liberal.

INTRODUCTION: The urine output criterion of 0.5 ml/kg/hour for 6 hours for acute kidney injury (AKI) has not been prospectively validated. Urine output criteria for AKI (AKIUO) as predictors of in-hospital mortality or dialysis need were compared. METHODS: All admissions to a general ICU were prospectively screened for 12 months and hourly urine output analysed in collection intervals between 1 and 12 hours. Prediction of the composite of mortality or dialysis by urine output was analysed in increments of 0.1 ml/kg/hour from 0.1 to 1 ml/kg/hour and the optimal threshold for each collection interval determined. AKICr was defined as an increase in plasma creatinine≥26.5 µmol/l within 48 hours or ≥50% from baseline. RESULTS: Of 725 admissions, 72% had either AKICr or AKIUO or both. AKIUO (33.7%) alone was more frequent than AKICr (11.0%) alone (P<0.0001). A 6-hour urine output collection threshold of 0.3 ml/kg/hour was associated with a stepped increase in in-hospital mortality or dialysis (from 10% above to 30% less than 0.3 ml/kg/hour). Hazard ratios for in-hospital mortality and 1-year mortality were 2.25 (1.40 to 3.61) and 2.15 (1.47 to 3.15) respectively after adjustment for age, body weight, severity of illness, fluid balance, and vasopressor use. In contrast, after adjustment AKIUO was not associated with in-hospital mortality or 1-year mortality. The optimal urine output threshold was linearly related to duration of urine collection (r2=0.93). CONCLUSIONS: A 6-hour urine output threshold of 0.3 ml/kg/hour best associated with mortality and dialysis, and was independently predictive of both hospital mortality and 1-year mortality. This suggests that the current AKI urine output definition is too liberally defined. Shorter urine collection intervals may be used to define AKI using lower urine output thresholds.

High-dose intravenous epoetin does not increase blood pressure in critically ill patients with acute kidney injury.

AIMS: Treatment of renal anemia with erythropoietic stimulating agents sometimes increases blood pressure. It is uncertain whether this is due to direct vasoconstriction and/or increased red blood cell mass. MATERIALS AND METHODS: We conducted a post-hoc analysis of 160 critically ill patients in the EARLYARF trial with elevated urinary γ-glutamyltranspeptidase and alkaline phosphatase, indicating acute kidney injury. Patients received 2 doses of intravenous (i.v.) epoetin (500 U/kg), 24 hours apart, or placebo, in a randomized, double-blind study design. Hourly intra-arterial mean arterial pressure (MAP), and norepinephrine equivalent dose (NED: determined using equipotency conversion factors for doses of epinephrine, vasopressin, phenlyephrine, or dopamine) were extracted from clinical records. The differences between baseline and maximum MAP and NED (ΔMAP and ΔNED) over 4, 24, 72-hour, and 30-day periods following study drug administration were compared between groups. RESULTS: At baseline, MAP was 78 ± 14 mmHg in the epoetin group and 81 ± 15 mmHg in the placebo group (p = 0.22). There were no differences between groups in ΔMAP (6 ± 14 versus 7 ± 14 mmHg; p = 0.53), in ΔNED, or in ΔMAP adjusted for ΔNED at 4 hours, or at any time points. A subgroup analysis of only those patients not requiring vasopressor support (n = 71) also showed no differences between epoetin and placebo for all outcomes. CONCLUSION: We concluded that intravenous high dose epoetin does not acutely increase blood pressure, suggesting no acute vasoconstrictor effect in this setting.

Test characteristics of urinary biomarkers depend on quantitation method in acute kidney injury.

The concentration of urine influences the concentration of urinary biomarkers of AKI. Whether normalization to urinary creatinine concentration, as commonly performed to quantitate albuminuria, is the best method to account for variations in urinary biomarker concentration among patients in the intensive care unit is unknown. Here, we compared the diagnostic and prognostic performance of three methods of biomarker quantitation: absolute concentration, biomarker normalized to urinary creatinine concentration, and biomarker excretion rate. We measured urinary concentrations of alkaline phosphatase, γ-glutamyl transpeptidase, cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and IL-18 in 528 patients on admission and after 12 and 24 hours. Absolute concentration best diagnosed AKI on admission, but normalized concentrations best predicted death, dialysis, or subsequent development of AKI. Excretion rate on admission did not diagnose or predict outcomes better than either absolute or normalized concentration. Estimated 24-hour biomarker excretion associated with AKI severity, and for neutrophil gelatinase-associated lipocalin and cystatin C, with poorer survival. In summary, normalization to urinary creatinine concentration improves the prediction of incipient AKI and outcome but provides no advantage in diagnosing established AKI. The ideal method for quantitating biomarkers of urinary AKI depends on the outcome of interest.

The Utility of the Creatinine Excretion to Production Ratio and the Plasma Creatinine and Cystatin C Based Kinetic Estimates of Glomerular Filtration Rates in Critically Ill Patients with Sepsis.

Introduction: Creatinine kinetics denotes that under steady-state conditions, creatinine production (G) will equal creatinine excretion rate (E). The glomerular filtration (GFR) is impaired when excretion is less than production. The kinetic estimate of GFR (keGFR) and E/G ratio were proposed as a more accurate estimate of GFR in acute settings with rapidly changing kidney function. We evaluated keGFR and E/G to diagnose AKI, predict recovery, death or dialysis. Methods: This is a prospective observational study of critically ill patients. Inclusion criteria were patients >18 years old with sepsis, defined as clinical infection with an increase in SOFA score >2, and plasma procalcitonin >0.5 ng/mL. Plasma creatinine and Cystatin C were measured on ICU admission and 4 h later, and their keGFR was calculated. Urine creatinine and urine output were measured over 4 h to calculate the E/G ratio. Results: A total of 70 patients were recruited, of which 49 (70%) had AKI. Of these, 33 recovered within 3 days, and 15 had a composite outcome of death or dialysis. Day 1 keGFRCr and keGFRCysC discriminated AKI from non-AKI with AUCs of 0.85 (95% Confidence interval: 0.74-0.96), and 0.86 (0.76-0.97), respectively. The E/G ratio predicted AKI recovery (AUC: 0.81 (0.69-0.97)). The keGFRs were not predictive of death or dialysis, whereas E/G was predictive (AUC: 0.76 (0.63-0.89). Conclusion: keGFR was strongly diagnostic of AKI. The E/G ratio predicted AKI recovery and a composite outcome of death and dialysis.

Development and Validation of Creatinine-Based Estimates of the Glomerular Filtration Rate Equation from 99mTc-DTPA Imaging in the Malaysian Setting.

INTRODUCTION: Accurate assessment of glomerular filtration rate (GFR) is very important for diagnostic and therapeutic intervention. Clinically, GFR is estimated from plasma creatinine using equations such as Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations. However, these were developed in the Western population. To the best of our knowledge, there was no equation that has been developed specifically in our population. OBJECTIVES: We developed a new equation based on the gold standard of 99mTc-DTPA imaging measured GFR. We then performed an internal validation by comparing the bias, precision, and accuracy of the new equation and the other equations with the gold standard of 99mTc-DTPA imaging measured GFR. METHODS: This was a cross-sectional study using the existing record of patients who were referred for 99mTc-DTPA imaging at the Nuclear Medicine Centre, International Islamic University Malaysia. As this is a retrospective study utilising routinely collected data from the existing pool of data, the ethical committee has waived the need for informed consent. RESULTS: Data of 187 patients were analysed from January 2016 to March 2021. Of these, 94 were randomised to the development cohort and 93 to the validation cohort. A new equation of eGFR was determined as 16.637 ∗ 0.9935Age ∗ (SCr/23.473)-0.45159. In the validation cohort, both CKD-EPI and the new equation had the highest correlation to 99mTc-DTPA with a correlation coefficient of 0.81 (p < 0.0001). However, the new equation had the least bias and was the most precise (mean bias of -3.58 ± 12.01) and accurate (P30 of 64.5% and P50 of 84.9%) compared to the other equations. CONCLUSION: The new equation which was developed specifically using our local data population was the most accurate and precise, with less bias compared to the other equations. Further study validating this equation in the perioperative and intensive care patients is needed.

Patient asynchrony modelling during controlled mechanical ventilation therapy.

BACKGROUND AND OBJECTIVE: Mechanical ventilation therapy of respiratory failure patients can be guided by monitoring patient-specific respiratory mechanics. However, the patient's spontaneous breathing effort during controlled ventilation changes airway pressure waveform and thus affects the model-based identification of patient-specific respiratory mechanics parameters. This study develops a model to estimate respiratory mechanics in the presence of patient effort. METHODS: Gaussian effort model (GEM) is a derivative of the single-compartment model with basis function. GEM model uses a linear combination of basis functions to model the nonlinear pressure waveform of spontaneous breathing patients. The GEM model estimates respiratory mechanics such as Elastance and Resistance along with the magnitudes of basis functions, which accounts for patient inspiratory effort. RESULTS AND DISCUSSION: The GEM model was tested using both simulated data and a retrospective observational clinical trial patient data. GEM model fitting to the original airway pressure waveform is better than any existing models when reverse triggering asynchrony is present. The fitting error of GEM model was less than 10% for both simulated data and clinical trial patient data. CONCLUSION: GEM can capture the respiratory mechanics in the presence of patient effect in volume control ventilation mode and also can be used to assess patient-ventilator interaction. This model determines basis functions magnitudes, which can be used to simulate any waveform of patient effort pressure for future studies. The estimation of parameter identification GEM model can further be improved by constraining the parameters within a physiologically plausible range during least-square nonlinear regression.

Assessment of Glycemic Control Protocol (STAR) Through Compliance Analysis Amongst Malaysian ICU Patients.

PURPOSE: This paper presents an assessment of an automated and personalized stochastic targeted (STAR) glycemic control protocol compliance in Malaysian intensive care unit (ICU) patients to ensure an optimized usage. PATIENTS AND METHODS: STAR proposes 1-3 hours treatment based on individual insulin sensitivity variation and history of blood glucose, insulin, and nutrition. A total of 136 patients recorded data from STAR pilot trial in Malaysia (2017-quarter of 2019*) were used in the study to identify the gap between chosen administered insulin and nutrition intervention as recommended by STAR, and the real intervention performed. RESULTS: The results show the percentage of insulin compliance increased from 2017 to first quarter of 2019* and fluctuated in feed administrations. Overall compliance amounted to 98.8% and 97.7% for administered insulin and feed, respectively. There was higher average of 17 blood glucose measurements per day than in other centres that have been using STAR, but longer intervals were selected when recommended. Control safety and performance were similar for all periods showing no obvious correlation to compliance. CONCLUSION: The results indicate that STAR, an automated model-based protocol is positively accepted among the Malaysian ICU clinicians to automate glycemic control and the usage can be extended to other hospitals already. Performance could be improved with several propositions.

Model-based glycemic control in a Malaysian intensive care unit: performance and safety study.

Background: Stress-induced hyperglycemia is common in critically ill patients. A few forms of model-based glycemic control have been introduced to reduce this phenomena and among them is the automated STAR protocol which has been used in the Christchurch and Gyulá hospitals' intensive care units (ICUs) since 2010. Methods: This article presents the pilot trial assessment of STAR protocol which has been implemented in the International Islamic University Malaysia Medical Centre (IIUMMC) Hospital ICU since December 2017. One hundred and forty-two patients who received STAR treatment for more than 20 hours were used in the assessment. The initial results are presented to discuss the ability to adopt and adapt the model-based control framework in a Malaysian environment by analyzing its performance and safety. Results: Overall, 60.7% of blood glucose measurements were in the target band. Only 0.78% and 0.02% of cohort measurements were below 4.0 mmol/L and 2.2 mmol/L (the limitsfor mild and severe hypoglycemia, respectively). Treatment preference-wise, the clinical staff were favorable of longer intervention options when available. However, 1 hourly treatments were still used in 73.7% of cases. Conclusion: The protocol succeeded in achieving patient-specific glycemic control while maintaining safety and was trusted by nurses to reduce workload. Its lower performance results, however, give the indication for modification in some of the control settings to better fit the Malaysian environment.

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 DESIGN: 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.

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 SMS was 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 sepsis mortality 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.

Assessing mechanical ventilation asynchrony through iterative airway pressure reconstruction.

BACKGROUND AND OBJECTIVE: Respiratory mechanics estimation can be used to guide mechanical ventilation (MV) but is severely compromised when asynchronous breathing occurs. In addition, asynchrony during MV is often not monitored and little is known about the impact or magnitude of asynchronous breathing towards recovery. Thus, it is important to monitor and quantify asynchronous breathing over every breath in an automated fashion, enabling the ability to overcome the limitations of model-based respiratory mechanics estimation during asynchronous breathing ventilation. METHODS: An iterative airway pressure reconstruction (IPR) method is used to reconstruct asynchronous airway pressure waveforms to better match passive breathing airway waveforms using a single compartment model. The reconstructed pressure enables estimation of respiratory mechanics of airway pressure waveform essentially free from asynchrony. Reconstruction enables real-time breath-to-breath monitoring and quantification of the magnitude of the asynchrony (MAsyn). RESULTS AND DISCUSSION: Over 100,000 breathing cycles from MV patients with known asynchronous breathing were analyzed. The IPR was able to reconstruct different types of asynchronous breathing. The resulting respiratory mechanics estimated using pressure reconstruction were more consistent with smaller interquartile range (IQR) compared to respiratory mechanics estimated using asynchronous pressure. Comparing reconstructed pressure with asynchronous pressure waveforms quantifies the magnitude of asynchronous breathing, which has a median value MAsyn for the entire dataset of 3.8%. CONCLUSION: The iterative pressure reconstruction method is capable of identifying asynchronous breaths and improving respiratory mechanics estimation consistency compared to conventional model-based methods. It provides an opportunity to automate real-time quantification of asynchronous breathing frequency and magnitude that was previously limited to invasively method only.