Mechanical Ventilation Discontinuation Practices in Asia: A Multinational Survey.

Rationale: There are limited data on mechanical discontinuation practices in Asia. Objectives: To document self-reported mechanical discontinuation practices and determine whether there is clinical equipoise regarding protocolized weaning among Asian Intensive Care specialists. Methods: A survey using a validated questionnaire, distributed using a snowball method to Asian Intensive Care specialists. Results: Of the 2,967 invited specialists from 20 territories, 2,074 (69.9%) took part. The majority of respondents (60.5%) were from China. Of the respondents, 42% worked in intensive care units (ICUs) where respiratory therapists were present; 78.9% used a spontaneous breathing trial as the initial weaning step; 44.3% frequently/always used pressure support (PS) alone, 53.4% intermittent spontaneous breathing trials with PS in between, and 19.8% synchronized intermittent mandatory ventilation with PS as a weaning mode. Of the respondents, 56.3% routinely stopped feeds before extubation, 71.5% generally followed a sedation protocol or guideline, and 61.8% worked in an ICU with a weaning protocol. Of these, 78.2% frequently always followed the protocol. A multivariate analysis involving a modified Poisson regression analysis showed that working in an ICU with a weaning protocol and frequently/always following it was positively associated with an upper-middle-income territory, a university-affiliated hospital, or in an ICU that employed respiratory therapists; and negatively with a low-income or lower-middle-income territory or a public hospital. There was no significant association with "in-house" intensivist at night, multidisciplinary ICU, closed ICU, or nurse-patient ratio. There was heterogeneity in agreement/disagreement with the statement, "evidence clearly supports protocolized weaning over nonprotocolized weaning." Conclusions: A substantial minority of Asian Intensive Care specialists do not wean patients in accordance with the best available evidence or current guidelines. There is clinical equipoise regarding the benefit of protocolized weaning.

Dengue Infection Complicated by Hemophagocytic Lymphohistiocytosis: Experiences From 180 Patients With Severe Dengue.

BACKGROUND: Globally, ~500 000 people with severe dengue (SD) require hospitalization yearly; ~12 500 (2.5%) die. Secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially fatal hyperinflammatory condition for which HLH-directed therapy (as etoposide and dexamethasone) can be life-saving. Prompted by the high mortality in SD and the increasing awareness that patients with SD may develop sHLH, our objectives were to (1) determine the frequency of dengue-HLH in SD, (2) describe clinical features of dengue-HLH, (3) assess mortality rate in SD and dengue-HLH, and (4) identify mortality-associated risk factors in SD. METHODS: A 5-year retrospective single-center study in all adult patients with SD admitted to a tertiary intensive care unit in Malaysia. RESULTS: Thirty-nine of 180 (22%) patients with SD died. Twenty-one of 180 (12%) had HLH defined as an HLH probability ≥70% according to histo score (HScore); 9 (43%) died. Similarly, 12 of 31 (39%) fulfilling ≥4 and 7 of 9 (78%) fulfilling ≥5 HLH-2004 diagnostic criteria died. Peak values of aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, and creatinine correlated to fatality (odds ratios [ORs], 2.9, 3.4, 5.8, and 31.9; all P < .0001), as did peak ferritin (OR, 2.5; P = .0028), nadir platelets (OR, 1.9; P = .00068), hepatomegaly (OR, 2.9; P = .012), and increasing age (OR, 1.2; P = .0043). Multivariable logistic regression revealed peak AST (OR, 2.8; P = .0019), peak creatinine (OR, 7.3; P = .0065), and SOFA (Sequential Organ Failure Assessment) score (OR, 1.4; P = .0051) as independent risk factors of death. CONCLUSIONS: Be observant of dengue-HLH due to its high mortality. A prospective study is suggested on prompt HLH-directed therapy in SD patients with hyperinflammation and evolving multiorgan failure at risk of developing dengue-HLH.

Withholding and withdrawal of life-sustaining treatments in low-middle-income versus high-income Asian countries and regions.

PURPOSE: To compare the attitudes of physicians towards withholding and withdrawing life-sustaining treatments in intensive care units (ICUs) in low-middle-income Asian countries and regions with those in high-income ones, and to explore differences in the role of families and surrogates, legal risks, and financial considerations between these countries and regions. METHODS: Questionnaire study conducted in May-December 2012 on 847 physicians from 255 ICUs in 10 low-middle-income countries and regions according to the World Bank's classification, and 618 physicians from 211 ICUs in six high-income countries and regions. RESULTS: After we accounted for personal, ICU, and hospital characteristics on multivariable analyses using generalised linear mixed models, physicians from low-middle-income countries and regions were less likely to limit cardiopulmonary resuscitation, mechanical ventilation, vasopressors and inotropes, tracheostomy and haemodialysis than those from high-income countries and regions. They were more likely to involve families in end-of-life care discussions and to perceive legal risks with limitation of life-sustaining treatments and do-not-resuscitate orders. Nonetheless, they were also more likely to accede to families' requests to withdraw life-sustaining treatments in a patient with an otherwise reasonable chance of survival on financial grounds in a case scenario (adjusted odds ratio 5.05, 95 % confidence interval 2.69-9.51, P < 0.001). CONCLUSIONS: Significant differences in ICU physicians' self-reported practice of limiting life-sustaining treatments, the role of families and surrogates, perception of legal risks and financial considerations exist between low-middle-income and high-income Asian countries and regions.

The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study).

INTRODUCTION: Despite evidence demonstrating the value of performance initiatives, marked differences remain between hospitals in the delivery of care for patients with sepsis. The aims of this study were to improve our understanding of how compliance with the 3-h and 6-h Surviving Sepsis Campaign (SSC) bundles are used in different geographic areas, and how this relates to outcome. METHODS: This was a global, prospective, observational, quality improvement study of compliance with the SSC bundles in patients with either severe sepsis or septic shock. RESULTS: A total of 1794 patients from 62 countries were enrolled in the study with either severe sepsis or septic shock. Overall compliance with all the 3-h bundle metrics was 19%. This was associated with lower hospital mortality than non-compliance (20 vs. 31%, p < 0.001). Overall compliance with all the 6-h bundle metrics was 36%. This was associated with lower hospital mortality than non-compliance (22 vs. 32%, p < 0.001). After adjusting the crude mortality differences for ICU admission, sepsis status (severe sepsis or septic shock), location of diagnosis, APACHE II score and country, compliance remained independently associated with improvements in hospital mortality for both the 3-h bundle (OR = 0.64 (95% CI 0.47-0.87), p = 0.004)) and 6-h bundle (OR = 0.71 (95% CI 0.56-0.90), p = 0.005)). DISCUSSION: Compliance with all of the evidence-based bundle metrics was not high. Patients whose care included compliance with all of these metrics had a 40% reduction in the odds of dying in hospital with the 3-h bundle and 36% for the 6-h bundle.

An External Independent Validation of APACHE IV in a Malaysian Intensive Care Unit.

INTRODUCTION: Intensive care unit (ICU) prognostic models are predominantly used in more developed nations such as the United States, Europe and Australia. These are not that popular in Southeast Asian countries due to costs and technology considerations. The purpose of this study is to evaluate the suitability of the acute physiology and chronic health evaluation (APACHE) IV model in a single centre Malaysian ICU. MATERIALS AND METHODS: A prospective study was conducted at the single centre ICU in Hospital Sultanah Aminah (HSA) Malaysia. External validation of APACHE IV involved a cohort of 916 patients who were admitted in 2009. Model performance was assessed through its calibration and discrimination abilities. A first-level customisation using logistic regression approach was also applied to improve model calibration. RESULTS: APACHE IV exhibited good discrimination, with an area under receiver operating characteristic (ROC) curve of 0.78. However, the model's overall fit was observed to be poor, as indicated by the Hosmer-Lemeshow goodness-of-fit test (C = 113, P <0.001). Predicted in-ICU mortality rate (28.1%) was significantly higher than the actual in-ICU mortality rate (18.8%). Model calibration was improved after applying first-level customisation (C = 6.39, P = 0.78) although discrimination was not affected. CONCLUSION: APACHE IV is not suitable for application in HSA ICU, without further customisation. The model's lack of fit in the Malaysian study is attributed to differences in the baseline characteristics between HSA ICU and APACHE IV datasets. Other possible factors could be due to differences in clinical practice, quality and services of health care systems between Malaysia and the United States.

Withholding and withdrawal of life-sustaining treatments in intensive care units in Asia.

IMPORTANCE: Little data exist on end-of-life care practices in intensive care units (ICUs) in Asia. OBJECTIVE: To describe physicians' attitudes toward withholding and withdrawal of life-sustaining treatments in end-of-life care and to evaluate factors associated with observed attitudes. DESIGN, SETTING, AND PARTICIPANTS: Self-administered structured and scenario-based survey conducted among 1465 physicians (response rate, 59.6%) who manage patients in ICUs (May-December 2012) at 466 ICUs (response rate, 59.4%) in 16 Asian countries and regions. RESULTS: For patients with no real chance of recovering a meaningful life, 1029 respondents (70.2%) reported almost always or often withholding whereas 303 (20.7%) reported almost always or often withdrawing life-sustaining treatments; 1092 respondents (74.5%) deemed withholding and withdrawal ethically different. The majority of respondents reported that vasopressors, hemodialysis, and antibiotics could usually be withheld or withdrawn in end-of-life care, but not enteral feeding, intravenous fluids, and oral suctioning. For severe hypoxic-ischemic encephalopathy after cardiac arrest, 1201 respondents (82.0% [range between countries, 48.4%-100%]) would implement do-not-resuscitate orders, but 788 (53.8% [range, 6.1%-87.2%]) would maintain mechanical ventilation and start antibiotics and vasopressors if indicated. On multivariable analysis, refusal to implement do-not-resuscitate orders was more likely with physicians who did not value families' or surrogates' requests (adjusted odds ratio [AOR], 1.67 [95% CI, 1.16-2.40]; P = .006), who were uncomfortable discussing end-of-life care (AOR, 2.38 [95% CI, 1.62-3.51]; P < .001), who perceived greater legal risk (AOR, 1.92 [95% CI, 1.26-2.94]; P = .002), and in low- to middle-income economies (AOR, 2.73 [95% CI, 1.56-4.76]; P < .001). Nonimplementation was less likely with physicians of Protestant (AOR, 0.36 [95% CI, 0.16-0.80]; P = .01) and Catholic (AOR, 0.22 [95% CI, 0.09-0.58]; P = .002) faiths, and when out-of-pocket health care expenditure increased (AOR, 0.98 per percentage of total health care expenditure [95% CI, 0.97-0.99]; P = .02). CONCLUSIONS AND RELEVANCE: Whereas physicians in ICUs in Asia reported that they often withheld but seldom withdrew life-sustaining treatments at the end of life, attitudes and practice varied widely across countries and regions. Multiple factors related to country or region, including economic, cultural, religious, and legal differences, as well as personal attitudes, were associated with these variations. Initiatives to improve end-of-life care in Asia must begin with a thorough understanding of these factors.

Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study.

PURPOSE: To ascertain the relationship among early (first 48 h) deep sedation, time to extubation, delirium and long-term mortality. METHODS: We conducted a multicentre prospective longitudinal cohort study in 11 Malaysian hospitals including medical/surgical patients (n = 259) who were sedated and ventilated ≥24 h. Patients were followed from ICU admission up to 28 days in ICU with 4-hourly sedation and daily delirium assessments and 180-day mortality. Deep sedation was defined as Richmond Agitation Sedation Score (RASS) ≤-3. RESULTS: The cohort had a mean (SD) age of 53.1 (15.9) years and APACHE II score of 21.3 (8.2) with hospital and 180-day mortality of 82 (31.7%) and 110/237 (46.4%). Patients were followed for 2,657 ICU days and underwent 13,836 RASS assessments. Midazolam prescription was predominant compared to propofol, given to 241 (93%) versus 72 (28%) patients (P < 0.0001) for 966 (39.6%) versus 183 (7.5%) study days respectively. Deep sedation occurred in (182/257) 71% patients at first assessment and in 159 (61%) patients and 1,658 (59%) of all RASS assessments at 48 h. Multivariable Cox proportional hazard regression analysis adjusting for a priori assigned covariates including sedative agents, diagnosis, age, APACHE II score, operative, elective, vasopressors and dialysis showed that early deep sedation was independently associated with longer time to extubation [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.89-0.97, P = 0.003], hospital death (HR 1.11, 95% CI 1.05-1.18, P < 0.001) and 180-day mortality (HR 1.09, 95% CI 1.04-1.15, P = 0.002), but not time to delirium (HR 0.98, P = 0.23). Delirium occurred in 114 (44%) of patients. CONCLUSION: Irrespective of sedative choice, early deep sedation was independently associated with delayed extubation and higher mortality, and thus was a potentially modifiable risk in interventional trials.

Fucosylation is a promising target for cancer diagnosis and therapy.

Oligosaccharides, sequences of carbohydrates conjugated to proteins and lipids, are arguably the most abundant and structurally diverse class of molecules. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. Recent advances in glycomics have identified several types of glyco-biomarkers containing fucosylation that are linked to certain types of cancer. Fucosylated alpha-fetoprotein (AFP) is widely used in the diagnosis of hepatocellular carcinoma because it is more specific than alpha-fetoprotein. High levels of fucosylated haptoglobin have also been found in sera of patients with various carcinomas. We have recently established a simple lectin-antibody ELISA to measure fucosylated haptoglobin and to investigate its clinical use. Cellular fucosylation is dependent upon fucosyltransferase activity and the level of its donor substrate, guanosine diphosphate (GDP)-fucose. GDP-mannose-4,6-dehydratase (GMDS) is a key enzyme involved in the synthesis of GDP-fucose. Mutations of GMDS found in colon cancer cells induced a malignant phenotype, leading to rapid growth in athymic mice resistant to natural killer cells. This review describes the role of fucosylated haptoglobin as a cancer biomarker, and discusses the possible biological role of fucosylation in cancer development.

Management of severe sepsis in patients admitted to Asian intensive care units: prospective cohort study.

OBJECTIVES: To assess the compliance of Asian intensive care units and hospitals to the Surviving Sepsis Campaign's resuscitation and management bundles. Secondary objectives were to evaluate the impact of compliance on mortality and the organisational characteristics of hospitals that were associated with higher compliance. DESIGN: Prospective cohort study. SETTING: 150 intensive care units in 16 Asian countries. PARTICIPANTS: 1285 adult patients with severe sepsis admitted to these intensive care units in July 2009. The organisational characteristics of participating centres, the patients' baseline characteristics, the achievement of targets within the resuscitation and management bundles, and outcome data were recorded. MAIN OUTCOME MEASURE: Compliance with the Surviving Sepsis Campaign's resuscitation (six hours) and management (24 hours) bundles. RESULTS: Hospital mortality was 44.5% (572/1285). Compliance rates for the resuscitation and management bundles were 7.6% (98/1285) and 3.5% (45/1285), respectively. On logistic regression analysis, compliance with the following bundle targets independently predicted decreased mortality: blood cultures (achieved in 803/1285; 62.5%, 95% confidence interval 59.8% to 65.1%), broad spectrum antibiotics (achieved in 821/1285; 63.9%, 61.3% to 66.5%), and central venous pressure (achieved in 345/870; 39.7%, 36.4% to 42.9%). High income countries, university hospitals, intensive care units with an accredited fellowship programme, and surgical intensive care units were more likely to be compliant with the resuscitation bundle. CONCLUSIONS: While mortality from severe sepsis is high, compliance with resuscitation and management bundles is generally poor in much of Asia. As the centres included in this study might not be fully representative, achievement rates reported might overestimate the true degree of compliance with recommended care and should be interpreted with caution. Achievement of targets for blood cultures, antibiotics, and central venous pressure was independently associated with improved survival.