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.

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.

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 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.

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.

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.

Performance of Stochastic Targeted Blood Glucose Control Protocol by virtual trials in the Malaysian intensive care unit.

BACKGROUND AND OBJECTIVE: Blood glucose variability is common in healthcare and it is not related or influenced by diabetes mellitus. To minimise the risk of high blood glucose in critically ill patients, Stochastic Targeted Blood Glucose Control Protocol is used in intensive care unit at hospitals worldwide. Thus, this study focuses on the performance of stochastic modelling protocol in comparison to the current blood glucose management protocols in the Malaysian intensive care unit. Also, this study is to assess the effectiveness of Stochastic Targeted Blood Glucose Control Protocol when it is applied to a cohort of diabetic patients. METHODS: Retrospective data from 210 patients were obtained from a general hospital in Malaysia from May 2014 until June 2015, where 123 patients were having comorbid diabetes mellitus. The comparison of blood glucose control protocol performance between both protocol simulations was conducted through blood glucose fitted with physiological modelling on top of virtual trial simulations, mean calculation of simulation error and several graphical comparisons using stochastic modelling. RESULTS: Stochastic Targeted Blood Glucose Control Protocol reduces hyperglycaemia by 16% in diabetic and 9% in nondiabetic cohorts. The protocol helps to control blood glucose level in the targeted range of 4.0-10.0 mmol/L for 71.8% in diabetic and 82.7% in nondiabetic cohorts, besides minimising the treatment hour up to 71 h for 123 diabetic patients and 39 h for 87 nondiabetic patients. CONCLUSION: It is concluded that Stochastic Targeted Blood Glucose Control Protocol is good in reducing hyperglycaemia as compared to the current blood glucose management protocol in the Malaysian intensive care unit. Hence, the current Malaysian intensive care unit protocols need to be modified to enhance their performance, especially in the integration of insulin and nutrition intervention in decreasing the hyperglycaemia incidences. Improvement in Stochastic Targeted Blood Glucose Control Protocol in terms of uen model is also a must to adapt with the diabetic cohort.

The diagnostic ability of procalcitonin and interleukin-6 to differentiate infectious from noninfectious systemic inflammatory response syndrome and to predict mortality.

PURPOSE: The purpose of the study was to quantify the ability of procalcitonin (PCT) and interleukin-6 (IL-6) to differentiate noninfectious systemic inflammatory response syndrome (SIRS) and sepsis and to predict hospital mortality. MATERIALS: We recruited consecutively adult patients with SIRS admitted to an intensive care unit. They were divided into sepsis and noninfectious SIRS based on clinical assessment with or without positive cultures. Concentrations of PCT and IL-6 were measured daily over the first 3 days. RESULTS: A total of 239 patients were recruited, 164 (68.6%) had sepsis, and 68 (28.5%) died in hospital. The PCT levels were higher in sepsis compared with noninfectious SIRS throughout the 3-day period (P < .0001). On admission, PCT concentration was diagnostic of sepsis (area under the curve of 0.63 [0.55-0.71]), and IL-6 was predictive of mortality, (area under the curve of 0.70 [0.62-0.78]). Peak IL-6 concentration improved the risk assessment of Sequential Organ Failure Assessment (SOFA) score for prediction of mortality among those who went on to die by an average of 5% and who did not die by 2% CONCLUSIONS: Procalcitonin measured on intensive care unit admission was diagnostic of sepsis, and IL-6 was predictive of mortality. Addition of IL-6 concentration to SOFA score improved risk assessment for prediction of mortality. Future studies should include clinical indices, for example, SOFA score, for prognostic evaluation of biomarkers.

Acute kidney injury in a Malaysian intensive care unit: Assessment of incidence, risk factors, and outcome.

PURPOSE: Acute kidney injury (AKI) is common and carries a high mortality rate. Most epidemiological studies were retrospective and were done in Western populations. We aim to assess its incidence using both urine output and creatinine criteria and its association with risk factors and outcome. MATERIAL AND METHODS: This was a single-center, prospective, observational study. All intensive care unit (ICU) patients older than 18 years were screened for inclusion in the study. Admission of less than 48 hours, postelective surgery, and ICU readmission were excluded. RESULTS: A total of 143 patients were recruited, of these, 65% had AKI, of which 18 (19%) were stage 1; 23 (25%), stage 2; and 52 (56%), stage 3. Independent risk factors for AKI include high Acute Physiology and Chronic Health Evaluation II score and septic shock (odds ratio of 1.20 [1.09-1.33] and 8.41 [1.49-47.6], respectively). Thirty-eight percent were classified as AKI based on creatinine and 61% as AKI based on urine output criteria, and, in 34%, both AKI based on creatinine and AKI based on urine output criteria were present. Acute kidney injury was an independent risk factor for mortality (hazard ratio of, 2.61 [1.06-6.42]). CONCLUSIONS: Acute kidney injury is common in our ICU, and almost half are of highest severity stage. Patients with high severity of illness and septic shock were at risk for AKI. The presence of AKI independently predicted mortality.

Procalcitonin clearance for early prediction of survival in critically ill patients with severe sepsis.

Introduction. Serum procalcitonin (PCT) diagnosed sepsis in critically ill patients; however, its prediction for survival is not well established. We evaluated the prognostic value of dynamic changes of PCT in sepsis patients. Methods. A prospective observational study was conducted in adult ICU. Patients with systemic inflammatory response syndrome (SIRS) were recruited. Daily PCT were measured for 3 days. 48 h PCT clearance (PCTc-48) was defined as percentage of baseline PCT minus 48 h PCT over baseline PCT. Results. 95 SIRS patients were enrolled (67 sepsis and 28 noninfectious SIRS). 40% patients in the sepsis group died in hospital. Day 1-PCT was associated with diagnosis of sepsis (AUC 0.65 (95% CI, 0.55 to 0.76)) but was not predictive of mortality. In sepsis patients, PCTc-48 was associated with prediction of survival (AUC 0.69 (95% CI, 0.53 to 0.84)). Patients with PCTc-48 > 30% were independently associated with survival (HR 2.90 (95% CI 1.22 to 6.90)). Conclusions. PCTc-48 is associated with prediction of survival in critically ill patients with sepsis. This could assist clinicians in risk stratification; however, the small sample size, and a single-centre study, may limit the generalisability of the finding. This would benefit from replication in future multicentre study.