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Management of dengue haemorrhagic fever/dengue shock syndrome

Lum LC

Malays J Pathol, 1993 Jun;15(1):29-33.
PMID: 8277786
Paediatric intensive care in Kuala Lumpur, Malaysia: a developing subspecialty

Goh AY, Lum LC, Chan PW

J Trop Pediatr, 1999 Dec;45(6):362-4.
PMID: 10667007

Paediatric intensive care in Malaysia is a developing subspecialty with an increasing number of specialists with a paediatric background being involved in the care of critically ill children. A part prospective and part retrospective review of 118 consecutive non-neonatal ventilated patients in University Hospital, Kuala Lumpur was carried out from 1 June 1995 to 31 December 1996 to study the clinical epidemiology and outcome in our paediatric intensive case unit (PICU). The mean age of the patients was 33.9 +/- 6.0 months (median 16 months). The main mode of admission was emergency (96.6 per cent) with an overall mortality rate of 42 per cent (50/118). The mean paediatric risk of mortality (PRISM) score was 20 +/- 0.98 SEM, with 53 per cent of patients having a score of over 30 per cent. Multiorgan dysfunction (MODS) was identified in 71 per cent of patients. Admission efficiency (mortality risk > 1 per cent) was 97 per cent. Standardized mortality rate using PRISM was an acceptable 1.06. The main diagnostic categories were respiratory (32 per cent), neurology (22 per cent), haematology-oncology (18 per cent); the aetiology of dysfunction was mainly infective. Non-survivors were older (29.5 vs. 13.8 months, p < 0.0001), had more severe illness (mean PRISM score 30 vs. 14, p < 0.0001), were more likely to develop MODS (96 vs. 53 per cent, p < 0.0001) and required more intervention and monitoring. Paediatric intensive care in Malaysia differs widely from that in developed countries in patient characteristics, severity of illness, and care modalities provided.
Fulltext Low-dose inhaled nitric oxide in term and near-term infants with hypoxic respiratory failure: a Malaysian experience

Goh AY, Lum LC, Roziah M

Med J Malaysia, 2001 Sep;56(3):336-40.
PMID: 11732080

Inhaled nitric oxide (iNO) improves oxygenation in term and near-term infants with persistent pulmonary hypertension of the newborn (PPHN) and decreases the need for treatment with extracorporeal membrane oxygenation (ECMO). This mode of treatment is currently being introduced in Malaysia. We report our preliminary experience using low dose inhaled nitric oxide (20 parts per million) in three newborn infants (meconium aspiration syndrome, primary PPHN and congenital diaphragmatic hernia) with severe PPHN who fulfilled criteria for ECMO with a mean oxygenation index (OI) of 40. Two of the infants showed rapid and sustained improvement in oxygenation with a reduction in oxygenation index (OI) over 24 hours. The infant with diaphragmatic hernia showed an initial improvement in OI, which was unsustained and subsequently died. All three infants did not show significant elevation of methemoglobin or nitrogen dioxide (NO2). Inhaled nitric oxide is an effective and safe treatment for severe PPHN that can be used in a developing country like Malaysia.
Severe bronchiolitis in Malaysian children

Chan PW, Goh AY, Lum LC

J Trop Pediatr, 2000 Aug;46(4):234-6.
PMID: 10996986

Twenty-two (42 per cent) out of 52 patients admitted with severe bronchiolitis to our Paediatric Intensive Care Unit required ventilation. Risk factors associated with ventilation included a younger mean age, female sex, low birthweight, failure to thrive and the presence of an underlying illness. Ventilated patients were also more likely to have a higher respiratory distress assessment index (RDAI) score, pneumonic infiltration on chest X-ray, lower serum sodium and a positive respiratory syncytial virus isolation in the tracheal secretion.
Fulltext Fulminant hepatitis in dengue infection

Lum LC, Lam SK, George R, Devi S

Southeast Asian J. Trop. Med. Public Health, 1993 Sep;24(3):467-71.
PMID: 8160054

Eight cases of liver failure and encephalopathy were observed among twenty cases of grade 3 and grade 4 dengue hemorrhagic fever/dengue shock syndrome admitted to the Department of Pediatrics, University Hospital, Kuala Lumpur from January 1990 to December 1991. All patients with deterioriation in mental status showed a marked increase in liver enzymes (aspartate and alanine aminotransaminases) and severe coagulopathy. Six patients needed cerebral protection, including ventilation, intravenous sedation and muscle relaxants. There was one death during the period of study and one case of residual hemiparesis in a boy who had, in addition, intracerebral hemorrhage. All other survivors had complete recovery of liver and neurological function.
Fulltext Classifying dengue: a review of the difficulties in using the WHO case classification for dengue haemorrhagic fever

Bandyopadhyay S, Lum LC, Kroeger A

Trop Med Int Health, 2006 Aug;11(8):1238-55.
PMID: 16903887 DOI: 10.1111/j.1365-3156.2006.01678.x

BACKGROUND: The current World Health Organisation (WHO) classification of dengue includes two distinct entities: dengue fever (DF) and dengue haemorrhagic fever (DHF)/dengue shock syndrome; it is largely based on pediatric cases in Southeast Asia. Dengue has extended to different tropical areas and older age groups. Variations from the original description of dengue manifestations are being reported.
OBJECTIVES: To analyse the experience of clinicians in using the dengue case classification and identify challenges in applying the criteria in routine clinical practice.
METHOD: Systematic literature review of post-1975 English-language publications on dengue classification.
RESULTS: Thirty-seven papers were reviewed. Several studies had strictly applied all four WHO criteria in DHF cases; however, most clinicians reported difficulties in meeting all four criteria and used a modified classification. The positive tourniquet test representing the minimum requirement of a haemorrhagic manifestation did not distinguish between DHF and DF. In cases of DHF thrombocytopenia was observed in 8.6-96%, plasma leakage in 6-95% and haemorrhagic manifestations in 22-93%. The low sensitivity of classifying DHF could be due to failure to repeat the tests or physical examinations at the appropriate time, early intravenous fluid therapy, and lack of adequate resources in an epidemic situation and perhaps a considerable overlap of clinical manifestations in the different dengue entities.
CONCLUSION: A prospective multi-centre study across dengue endemic regions, age groups and the health care system is required which describes the clinical presentation of dengue including simple laboratory parameters in order to review and if necessary modify the current dengue classification.
Fulltext A review of dengue research in Malaysia

Cheah WK, Ng KS, Marzilawati AR, Lum LC

Med J Malaysia, 2014 Aug;69 Suppl A:59-67.
PMID: 25417953 MyJurnal

Dengue infection is a major cause of morbidity and mortality in Malaysia. To date, much research on dengue infection conducted in Malaysia have been published. One hundred and sixty six articles related to dengue in Malaysia were found from a search through a database dedicated to indexing all original data relevant to medicine published between the years 2000-2013. Ninety articles with clinical relevance and future research implications were selected and reviewed. These papers showed evidence of an exponential increase in the disease epidemic and a varying pattern of prevalent dengue serotypes at different times. The early febrile phase of dengue infection consist of an undifferentiated fever. Clinical suspicion and ability to identify patients at risk of severe dengue infection is important. Treatment of dengue infection involves judicious use of volume expander and supportive care. Potential future research areas are discussed to narrow our current knowledge gaps on dengue infection.
Hemophagocytosis in dengue: comprehensive report of six cases

Tan LH, Lum LC, Omar SF, Kan FK

J Clin Virol, 2012 Sep;55(1):79-82.
PMID: 22789140 DOI: 10.1016/j.jcv.2012.06.005

Hemophagocytic syndrome is a potentially fatal disorder. It is being increasingly reported but remained under-recognized in dengue. Most reported cases were in association with plasma leakage and shock but multi-organ impairment was also observed. We describe the time-lines of 6 cases of confirmed dengue with varying severities of hemophagocytosis. All had persistent fever, cytopenia and elevated transaminases with markedly elevated ferritin levels during and beyond the plasma leakage phase. Acute renal failure and central nervous system manifestation were observed in two patients. Morphological hemophagocytosis was demonstrated in three patients. All survivors showed clinical and biochemical resolution of hemophagocytosis indicating its transient nature. Persistence of fever and cytopenia together with multi-organ dysfunction, out of proportion to and beyond the plasma leakage phase should prompt clinicians to consider this phenomenon.
Mycoplasma Pneumoniae infection in Malaysian children admitted with community acquired pneumonia

Chan PW, Lum LC, Ngeow YF, Yasim MY

Southeast Asian J. Trop. Med. Public Health, 2001 Jun;32(2):397-401.
PMID: 11556595

Mycoplasma pneumoniae is increasingly recognized as an important cause of community acquired pneumonia (CAP) in children. We determined the importance of M. pneumoniae as a causative agent in 170 children aged 1 month to 15 years who were hospitalized with CAP over a 6-month period. The diagnosis of M. pneumoniae infection was based on serological evidence obtained by a particle agglutination test (SERODIA-MYCO II). A positive serological diagnosis was made if the acute phase serum titer was more than 1:160 or paired samples taken 2-4 weeks apart showed a four-fold or greater rise in the serum titer. M. pneumoniae was identified as the causative agent in 40 (23.5%) children. Children with M. pneumoniae infection were more likely to be older than 3 years (OR 4.0 95%CI 1.8-9.1, p<0.001), Chinese (OR 4.3 95%CI 2.0-8.9, p<0.001), have a duration of illness longer than 7 days prior to admission (OR 6.0 95%CI 2.7-13.5, p<0.001) and have perihilar interstitial changes on chest X-ray (OR 4.6 95%CI 2.2-9.9, p<0.001). A significant number of hospital admissions for CAP in Malaysian children can be attributed to M. pneumoniae. It is important to identify these children so as to administer the most appropriate antibiotic treatment.
Impact of 24 hour critical care physician staffing on case-mix adjusted mortality in paediatric intensive care

Goh AY, Lum LC, Abdel-Latif ME

Lancet, 2001 Feb 10;357(9254):445-6.
PMID: 11273070

The 24 h availability of intensive care consultants (intensivists) has been shown to improve outcomes in adult intensive care units (ICU) in the UK. We tested whether such availability would improve standardised mortality ratios when compared to out-of-hours cover by general paediatricians in the paediatric ICU setting of a medium-income developing country. The standardised mortality ratio (SMR) improved significantly from 1.57 (95%CI 1.25-1.95) with non-specialist care to 0.88 (95%CI 0.63-1.19) with intensivist care (rate ratio 0.56, 95% CI 0.47-0.67). Mortality odds ratio decreased by 0.234, 0.246 and 0.266 in the low, moderate and high-risk patients. 24 h availability of intensivists was associated with improved outcomes and use of resources in paediatric intensive care in a developing country.
Withdrawal and limitation of life support in paediatric intensive care

Goh AY, Lum LC, Chan PW, Bakar F, Chong BO

Arch Dis Child, 1999 May;80(5):424-8.
PMID: 10208946

OBJECTIVES: To compare the modes of death and factors leading to withdrawal or limitation of life support in a paediatric intensive care unit (PICU) in a developing country.
METHODS: Retrospective analysis of all children (< 12 years) dying in the PICU from January 1995 to December 1995 and January 1997 to June 1998 (n = 148).
RESULTS: The main mode of death was by limitation of treatment in 68 of 148 patients, failure of active treatment including cardiopulmonary resuscitation in 61, brain death in 12, and withdrawal of life support with removal of endotracheal tube in seven. There was no significant variation in the proportion of limitation of treatment, failure of active treatment, and brain death between the two periods; however, there was an increase in withdrawal of life support from 0% in 1995 to 8% in 1997-98. Justification for limitation was based predominantly on expectation of imminent death (71 of 75). Ethnic variability was noted among the 14 of 21 patients who refused withdrawal. Discussions for care restrictions were initiated almost exclusively by paediatricians (70 of 75). Diagnostic uncertainty (36% v 4.6%) and presentation as an acute illness were associated with the use of active treatment.
CONCLUSIONS: Limitation of treatment is the most common mode of death in a developing country's PICU and active withdrawal is still not widely practised. Paediatricians in developing countries are becoming more proactive in managing death and dying but have to consider sociocultural and religious factors when making such decisions.
Dengue encephalitis: a true entity?

Lum LC, Lam SK, Choy YS, George R, Harun F

Am J Trop Med Hyg, 1996 Mar;54(3):256-9.
PMID: 8600761 DOI: 10.4269/ajtmh.1996.54.256

Involvement of the central nervous system in dengue fever and dengue hemorrhagic fever has always been thought to be secondary to vasculitis with resultant fluid extravasation, cerebral edema, hypoperfusion, hyponatremia, liver failure, and/or renal failure. Thus, the condition has been referred to as dengue encephalopathy. Encephalitis or direct involvement of the brain by the virus was thought to be unlikely. This paper reports on six children who were seen over a period of two years presenting on the second or third day of illness with dengue encephalitis. The diagnosis was based upon a clinical picture of encephalitis and confirmed by cerebrospinal fluid (CSF) microscopy and electroencephalography changes. All six cases were confirmed dengue infections. Dengue 3 virus was isolated from the CSF of four cases and in one case, dengue 2 was detected by the polymerase chain reaction in both the CSF and blood. In the sixth case, virologic evidence was negative but dengue immunoglobulin M was detected in the CSF and blood. Since the onset of encephalitis appears early in the course of illness coinciding with the viremic phase, we postulate that the virus crosses the blood-brain barrier and directly invades the brain causing encephalitis. This study provides strong evidence that dengue 2 and 3 viruses have neurovirulent properties and behave similarly to other members of the Flaviviridae.
Incidence of acute respiratory distress syndrome: a comparison of two definitions

Goh AY, Chan PW, Lum LC, Roziah M

Arch Dis Child, 1998 Sep;79(3):256-9.
PMID: 9875023

OBJECTIVES: To determine the incidence and outcome of acute respiratory distress syndrome (ARDS) in children by comparing two commonly used definitions: the lung injury score and the American-European Consensus Conference definition. The causes and risk for developing ARDS were also studied.
METHODS: Part prospective and retrospective analysis of 8100 consecutive hospital admissions from 1 June 1995 to 1 April 1997.
RESULTS: Twenty one patients fulfilled the criteria for ARDS. Both definitions identified the same group of patients. The incidence was 2.8/1000 hospital admissions or 4.2% of paediatric intensive care unit admissions. The main causes were sepsis and pneumonia. Mortality was 13 of 21. Factors predicting death were a high admission paediatric risk of mortality (PRISM) score (30.38 v 18.75) and the presence of multiple organ dysfunction syndrome (92% v 25%).
CONCLUSION: Both definitions identified similar groups of patients. The incidence in this population was higher than that reported elsewhere, but mortality and cause were similar to those in developed countries. Poor outcome was associated with sepsis, a high admission PRISM score, and simultaneous occurrence of other organ dysfunction.
Dengue-associated adult respiratory distress syndrome

Lum LC, Thong MK, Cheah YK, Lam SK

Ann Trop Paediatr, 1995 Dec;15(4):335-9.
PMID: 8687212 DOI: 10.1080/02724936.1995.11747794

In dengue shock syndrome, an acute increase in capillary permeability results in leakage of plasma into the interstitial space. Pleural effusion is commonly seen in dengue shock syndrome. We report three cases of dengue-associated adult respiratory distress syndrome (ARDS) in children, in all of whom dengue haemorrhagic fever, presenting with grade 3 or grade 4 dengue shock syndrome with disseminated intravascular coagulopathy, was confirmed. The criteria for the diagnosis of ARDS were based on the expanded definition of ARDS by Murray et al. Treatment consisted of fluid resuscitation, correction of coagulopathy and mechanical ventilation. All three children had multi-organ impairment, but it was more severe in the two who died. The one survivor was well at discharge.
Fulltext Regular paracetamol in severe dengue: a lethal combination?

Gan CS, Chong SY, Lum LC, Lee WS

Singapore Med J, 2013 Feb;54(2):e35-7.
PMID: 23462840

An eight-month-old female infant with severe dengue disease, who was repeatedly given therapeutic paracetamol for severe dengue, developed fulminant liver failure with encephalopathy, gastrointestinal haemorrhage and severe coagulopathy. She responded to supportive measures and N-acetylcysteine infusion. This case highlights the potential danger of administering repeated therapeutic doses of paracetamol in childhood severe dengue disease with hepatitis.
Fulltext Cytokine factors present in dengue patient sera induces alterations of junctional proteins in human endothelial cells

Appanna R, Wang SM, Ponnampalavanar SA, Lum LC, Sekaran SD

Am J Trop Med Hyg, 2012 Nov;87(5):936-42.
PMID: 22987650 DOI: 10.4269/ajtmh.2012.11-0606

Plasma leakage in severe dengue has been postulated to be associated with skewed cytokine immune responses. In this study, the association of cytokines with vascular permeability in dengue patients was investigated. Human serum samples collected from 48 persons (13 with dengue fever, 29 with dengue hemorrhagic fever, and 6 healthy) were subjected to cytokines analysis by using Luminex Multiplex Technology. Selected serum samples from patients with dengue hemorrhagic fever sera and recombinant human cytokines were then tested for roles on inducing vascular permeability by treatment of human umbilical vein endothelial cells. Confocal immunofluorescence staining indicated morphologic alteration of human umbilical vein endothelial cells treated with serum samples from patients with dengue hemorrhagic fever compared with serum samples from healthy persons. The findings suggest that cytokines produced during dengue hemorrhagic infections could induce alterations in the vascular endothelium, which may play a fundamental role in the pathophysiology of dengue.
Noninvasive ventilation in a tertiary pediatric intensive care unit in a middle-income country

Lum LC, Abdel-Latif ME, de Bruyne JA, Nathan AM, Gan CS

Pediatr Crit Care Med, 2011 Jan;12(1):e7-13.
PMID: 20190672 DOI: 10.1097/PCC.0b013e3181d505f4

To determine the factors that predict outcome of noninvasive ventilation (NIV) in critically ill children.
Fulltext Quality of life of dengue patients

Lum LC, Suaya JA, Tan LH, Sah BK, Shepard DS

Am J Trop Med Hyg, 2008 Jun;78(6):862-7.
PMID: 18541760

Although the disease burden of dengue is increasing, the impact on the quality of life (QoL) has not been investigated. A study to determine the QoL of confirmed dengue patients using the EuroQol visual thermometer scale was carried out at the University Malaya Medical Center. Of the 207 participants, 40% were ambulatory and 60% were hospitalized. Of eight health domains, 6.2 and 5.0 domains were affected in the hospitalized and ambulatory cohorts, respectively (P < 0.001), with cognition and interpersonal activities affected most. All patients experienced a drastic decrease in their QoL from the onset of symptoms. The QoL deteriorated to the lowest point (40% of healthy status) between the third and seventh days of illness. The duration of impaired QoL (9 days for ambulatory or 13 days for hospitalized patients) was longer than the duration of fever (5 and 7 days, respectively). Symptomatic dengue has major effects on patients' health.

Study site: e outpatient or inpatient care at the University Malaya Medical
Center.
Clinicians' diagnostic practice of dengue infections

Ng CF, Lum LC, Ismail NA, Tan LH, Tan CP

J Clin Virol, 2007 Nov;40(3):202-6.
PMID: 17928264 DOI: 10.1016/j.jcv.2007.08.017

BACKGROUND: Difficulties in the classification of dengue infection have been documented. Such difficulties could be due to the low awareness of the World Health Organization diagnostic guidelines among clinicians.
OBJECTIVE: To study the diagnostic practices of clinicians in classifying patients as dengue fever (DF) or dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS) at the time of discharge during an outbreak.
METHODS: A prospective descriptive study of clinical features and disease classification in adult and pediatric dengue patients in the University of Malaya Medical Centre.
RESULTS: Five hundred and twenty adult and 191 pediatric patients were enrolled. Thrombocytopenia and evidence of plasma leakage were present in 8% of adult and 19% of pediatric patients. Of these, 93% and 49%, respectively, were given the discharge diagnoses of DF instead of DHF/DSS. Hemoconcentration, serous effusion and thrombocytopenia were not recognized in clinicians' discharge diagnosis of DHF/DSS for adult patients. The receiver operating characteristic (ROC) curve suggested a lack of consistency in the use of WHO guidelines in establishing DHF/DSS in adult patients, while implying otherwise for pediatric patients.
CONCLUSION: DHF/DSS is an under-recognized condition by clinicians managing these patients. This can affect the case fatality rate of DHF/DSS and the economic burden of the disease. The lack of awareness in disease manifestations especially plasma leakage, can lead to delayed recognition of DHF/DSS.
Study site: Outpatient department and inpatients, adult medical and pediatric wards, University Malaya Medical Center (UMMC), Kuala Lumpur, Malaysia
Fulltext Cohorting Dengue Patients Improves the Quality of Care and Clinical Outcome

Lum LC, Syed Omar SF, Sri La Sri Ponnampalavanar S, Tan LH, Sekaran SD, Kamarulzaman A

PLoS Negl Trop Dis, 2015 Jun;9(6):e0003836.
PMID: 26047325 DOI: 10.1371/journal.pntd.0003836

INTRODUCTION: The increasing incidence of dengue among adults in Malaysia and other countries has important implications for health services. Before 2004, in order to cope with the surge in adult dengue admissions, each of the six medical wards in a university hospital took turns daily to admit and manage patients with dengue. Despite regular in-house training, the implementation of the WHO 1997 dengue case management guidelines by the multiple medical teams was piecemeal and resulted in high variability of care. A restructuring of adult dengue inpatient service in 2004 resulted in all patients being admitted to one ward under the care of the infectious disease unit. Hospital and Intensive Care Unit admission criteria, discharge criteria and clinical laboratory testing were maintained unchanged throughout the study period.
OBJECTIVES: To evaluate the impact of cohorting adult dengue patients on the quality of care and the clinical outcome in a university hospital in Malaysia.
METHODS: A pre (2003) and post-intervention (2005-6) retrospective study was undertaken.
INTERVENTION: Cohorting all dengue patients under the care of the Infectious Disease team in a designated ward in 2004.
RESULTS: The number of patients enrolled was 352 in 2003, 785 in 2005 and 1158 in 2006. The evaluation and detection of haemorrhage remained high (>90%) and unchanged throughout the study period. The evaluation of plasma leakage increased from 35.4% pre-intervention to 78.8% post-intervention (p = <0.001) while its detection increased from 11.4% to 41.6% (p = <0.001). Examination for peripheral perfusion was undertaken in only 13.1% of patients pre-intervention, with a significant increase post-intervention, 18.6% and 34.2% respectively, p = <0.001. Pre-intervention, more patients had hypotension (21.5%) than detected peripheral hypoperfusion (11.4%), indicating that clinicians recognised shock only when patients developed hypotension. In contrast, post-intervention, clinicians recognised peripheral hypoperfusion as an early sign of shock. The highest haematocrit was significantly higher post-intervention but the lowest total white cell counts and platelet counts remained unchanged. A significant and progressive reduction in the use of platelet transfusions occurred, from 21.7% pre-intervention to 14.6% in 2005 and 5.2% in 2006 post-intervention, p<0.001. Likewise, the use of plasma transfusion decreased significantly from 6.1% pre-intervention to 4.0% and 1.6% in the post-intervention years of 2005 and 2006 respectively, p<0.001. The duration of intravenous fluid therapy decreased from 3 days pre-intervention to 2.5 days (p<0.001) post-intervention; the length of hospital stay reduced from 4 days pre- to 3 days (p<0.001) post-intervention and the rate of intensive care admission from 5.8% pre to 2.6% and 2.5% post-intervention, p = 0.005.
CONCLUSION: Cohorting adult dengue patients under a dedicated and trained team of doctors and nurses led to a substantial improvement in quality of care and clinical outcome.

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