Huynh Thi Loan

Fluid Replacement in Dengue Shock Syndrome: A Randomized, Double-Blind Comparison of Four Intravenous-Fluid Regimens

Dengue hemorrhagic fever and dengue shock syndrome (DSS) are major causes of childhood morbidity and mortality in many tropical countries. Increased intravascular permeability leading to shock is the cardinal feature of DSS. Fluid resuscitation to counteract massive plasma leakage is the mainstay of treatment. A double-blind, randomized trial comparing four intravenous-fluid regimens for acute resuscitation of 50 children with DSS was conducted. Colloids (dextran 70 or the protein digest gelafundin 35,000) restored cardiac index and blood pressure and normalized hematocrit more rapidly than crystalloids (Ringers lactate or 0.9%-weight/volume saline). Dextran 70 provided the most rapid normalization of the hematocrit and restoration of the cardiac index, without adverse effects, and may be the preferred solution for acute resuscitation in DSS. Further large-scale double-blind trials are required to provide an evidence-based approach to the management of DSS.

Magnesium sulphate for treatment of severe tetanus: a randomised controlled trial

BACKGROUND The most common cause of death in individuals with severe tetanus in the absence of mechanical ventilation is spasm-related respiratory failure, whereas in ventilated patients it is tetanus-associated autonomic dysfunction. Our aim was to determine whether continuous magnesium sulphate infusion reduces the need for mechanical ventilation and improves control of muscle spasms and autonomic instability. METHODS We did a randomised, double blind, placebo controlled trial in 256 Vietnamese patients over age 15 years with severe tetanus admitted to the Hospital for Tropical Medicine, Ho Chi Minh City, Vietnam. Participants were randomly assigned magnesium sulphate (n=97) or placebo solution (n=98) intravenously for 7 days. The primary outcomes were requirement of assisted ventilation and of drugs to control muscle spasms and cardiovascular instability within the 7-day study period. Analyses were done by intention to treat. This trial is registered as an International Standard Randomised Clinical Trial, number ISRCTN74651862. FINDINGS No patients were lost to follow-up. There was no difference in requirement for mechanical ventilation between individuals treated with magnesium and those receiving placebo (odds ratio 0.71, 95% CI 0.36-1.40; p=0.324); survival was also much the same in the two groups. However, compared with the placebo group, patients receiving magnesium required significantly less midazolam (7.1 mg/kg per day [0.1-47.9] vs 1.4 mg/kg per day [0.0-17.3]; p=0.026) and pipecuronium (2.3 mg/kg per day [0.0-33.0] vs 0.0 mg/kg per day [0.0-14.8]; p=0.005) to control muscle spasms and associated tachycardia. Individuals receiving magnesium were 4.7 (1.4-15.9) times less likely to require verapamil to treat cardiovascular instability than those in the placebo group. The incidence of adverse events was not different between the groups. INTERPRETATION Magnesium infusion does not reduce the need for mechanical ventilation in adults with severe tetanus but does reduce the requirement for other drugs to control muscle spasms and cardiovascular instability.

Emergence of carbapenem-resistant Acinetobacter baumannii as the major cause of ventilator- associated pneumonia in intensive care unit patients at an infectious disease hospital in southern Vietnam

Ventilator-associated pneumonia (VAP) is a serious healthcare-associated infection that affects up to 30 % of intubated and mechanically ventilated patients in intensive care units (ICUs) worldwide. The bacterial aetiology and corresponding antimicrobial susceptibility of VAP is highly variable, and can differ between countries, national provinces and even between different wards in the same hospital. We aimed to understand and document changes in the causative agents of VAP and their antimicrobial susceptibility profiles retrospectively over an 11 year period in a major infectious disease hospital in southern Vietnam. Our analysis outlined a significant shift from Pseudomonas aeruginosa to Acinetobacter spp. as the most prevalent bacteria isolated from quantitative tracheal aspirates in patients with VAP in this setting. Antimicrobial resistance was common across all bacterial species and we found a marked proportional annual increase in carbapenem-resistant Acinetobacter spp. over a 3 year period from 2008 (annual trend; odds ratio 1.656, P = 0.010). We further investigated the possible emergence of a carbapenem-resistant Acinetobacter baumannii clone by multiple-locus variable number tandem repeat analysis, finding a blaOXA-23-positive strain that was associated with an upsurge in the isolation of this pathogen. We additionally identified a single blaNDM-1-positive A. baumannii isolate. This work highlights the emergence of a carbapenem-resistant clone of A. baumannii and a worrying trend of antimicrobial resistance in the ICU of the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.

Effect of magnesium sulphate on urinary catecholamine excretion in severe tetanus.

Severe tetanus is characterised by muscle spasms and autonomic dysfunction. We recently reported the results of a randomised placebo controlled trial of magnesium sulphate infusions for the treatment of severe tetanus which showed magnesium was associated with improved muscle spasm and cardiovascular control. We hypothesised that magnesium controlled autonomic dysfunction by reducing catecholamine release and thus urinary excretion. Urinary adrenaline and noradrenaline concentrations were measured during the first 24 h of therapy in 180 adults with severe tetanus randomised to treatment with magnesium (n = 92) or placebo (n = 88). Magnesium therapy was associated with lower urinary adrenaline excretion and higher urinary noradrenaline excretion. High urinary adrenaline concentrations were associated with documented autonomic dysfunction. Patients given magnesium had significantly less autonomic dysfunction, required less cardiovascular stabilising drugs, and had lower urinary concentrations of adrenaline. These findings suggest adrenaline is important in the pathophysiology of severe tetanus and magnesium controls autonomic dysfunction by reducing adrenaline release.

Semi-recumbent body position fails to prevent healthcare-associated pneumonia in Vietnamese patients with severe tetanus.

Healthcare-associated pneumonia (HCAP) is a common complication in patients with severe tetanus. Nursing tetanus patients in a semi-recumbent body position could reduce the incidence of HCAP. In a randomised controlled trial we compared the occurrence of HCAP in patients with severe tetanus nursed in a semi-recumbent (30°) or supine position. A total of 229 adults and children (aged ≥1 year) with severe tetanus admitted to hospital in Vietnam, were randomly assigned to a supine (n = 112) or semi-recumbent (n = 117) position. For patients maintaining their assigned positions and in hospital for > 48 h there was no significant difference between the two groups in the frequency of clinically suspected pneumonia [22/106 (20.8%) vs 26/104 (25.0%); p = 0.464], pneumonia rate/1000 intensive care unit days (13.9 vs 14.6; p = 0.48) and pneumonia rate/1000 ventilated days (39.2 vs 38.1; p = 0.72). Mortality in the supine patients was 11/112 (9.8%) compared with 17/117 (14.5%) in the semi-recumbent patients (p = 0.277). The overall complication rate [57/112 (50.9%) vs 76/117 (65.0%); p = 0.03] and need for tracheostomy [51/112 (45.5%) vs 69/117 (58.9%); p = 0.04) was greater in semi-recumbent patients. Semi-recumbent body positioning did not prevent the occurrence of HCAP in severe tetanus patients. [Clinical Trials.gov Identifier: NCT01331252]

In vitro activity of colistin in antimicrobial combination against carbapenem-resistant Acinetobacter baumannii isolated from patients with ventilator-associated pneumonia in Vietnam

Acinetobacter baumannii has become one of the major infection threats in intensive care units (ICUs) globally. Since 2008, A. baumannii has been the leading cause of ventilator-associated pneumonia (VAP) in our ICU at an infectious disease hospital in southern Vietnam. The emergence of this pathogen in our setting is consistent with the persistence of a specific clone exhibiting resistance to carbapenems. Antimicrobial combinations may be a strategy to treat infections caused by these carbapenem-resistant A. baumannii. Therefore, we assessed potential antimicrobial combinations against local carbapenem-resistant A. baumannii by measuring in vitro interactions of colistin with four antimicrobials that are locally certified for treating VAP. We first performed antimicrobial susceptibility testing and multilocus variable number tandem repeat analysis (MLVA) genotyping on 74 A. baumannii isolated from quantitative tracheal aspirates from patients with VAP over an 18-month period. These 74 isolates could be subdivided into 21 main clusters by MLVA and >80 % were resistant to carbapenems. We selected 56 representative isolates for in vitro combination synergy testing. Synergy was observed in four (7 %), seven (13 %), 20 (36 %) and 38 (68 %) isolates with combinations of colistin with ceftazidime, ceftriaxone, imipenem and meropenem, respectively. Notably, more carbapenem-resistant A. baumannii isolates (36/43; 84 %) exhibited synergistic activity with a combination of colistin and meropenem than carbapenem-susceptible A. baumannii isolates (2/13; 15 %) (P = 0.023; Fishers exact test). Our findings suggest that combinations of colistin and meropenem should be considered when treating carbapenem-resistant A. baumannii infections in Vietnam, and we advocate clinical trials investigating combination therapy for VAP.

Prognosis of neonatal tetanus in the modern management era: an observational study in 107 Vietnamese infants

Highlights • Large contemporary case-series in a setting of improved critical care facilities.• Analysis of variables, some not analysed in previous studies/meta-analyses.• Age and weight were associated with a poor outcome.• Delay in admission to hospital and leukocytosis were also associated with a poor outcome.

Tetanus in Southern Vietnam: Current Situation

In Vietnam, there are no accurate data on tetanus incidence to allow assessment of disease burden or vaccination program efficacy. We analyzed age structure of 786 tetanus cases admitted to a tertiary referral center in Vietnam for three separate years during an 18-year period to examine the impact of tetanus prevention programs, namely the Expanded Program on Immunization (EPI) and the Maternal and Neonatal Tetanus (MNT) initiative. Most cases were born before the initiation of EPI. Median age increased from 33 (interquartile range: 20–52) in 1994, to 46 (32–63) in 2012 (P < 0.001). Birth-year distribution was unchanged, indicating the same birth cohorts presented with tetanus in 1994, 2003, and 2012. Enzyme-linked immunosorbent assay measurements in 90 men and 90 women covered by MNT but not EPI showed 73.3% (95% confidence interval [CI]: 62.9–82.1%) of women had anti-tetanus antibody compared with 24.4% (95% CI: 15.9–34.7%) of men, indicating continued tetanus vulnerability in older men in Vietnam.

Polymorphisms of the gene coding for copper/zinc superoxide dismutase (SOD1) in patients with Japanese encephalitis

Abstract Japanese encephalitis is the commonest form of encephalitis globally. Most cases develop characteristic encephalitis but some also present with flaccid paralysis. The paralysis is secondary to damage at the alpha motor neurone, the site that is also damaged in amyotrophic lateral sclerosis (ALS). The gene coding for superoxide dismutase 1 (SOD1) is thought to be involved in ALS and may also be linked to susceptibility to Japanese encephalitis. To investigate this possibility, polymorphisms in the SOD1 gene were investigated, in 61 cases of Japanese encephalitis, 61 matched controls and 171 population controls, in Vietnam. Novel polymorphisms, found only in three of the cases and one of the population controls, may be involved with susceptibility to Japanese encephalitis and potentially to other flavivirus infections that lead to damage to the cells of the anterior horn. Further research on this possible association is required.

Continuous versus intermittent endotracheal cuff pressure control for the prevention of ventilator-associated respiratory infections in Vietnam: study protocol for a randomised controlled trial

BackgroundVentilator-associated respiratory infection (VARI) comprises ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). Although their diagnostic criteria vary, together these are the most common hospital-acquired infections in intensive care units (ICUs) worldwide, responsible for a large proportion of antibiotic use within ICUs. Evidence-based strategies for the prevention of VARI in resource-limited settings are lacking. Preventing the leakage of oropharyngeal secretions into the lung using continuous endotracheal cuff pressure control is a promising strategy. The aim of this study is to investigate the efficacy of automated, continuous endotracheal cuff pressure control in preventing the development of VARI and reducing antibiotic use in ICUs in Vietnam.Methods/designThis is an open-label randomised controlled multicentre trial. We will enrol 600 adult patients intubated for ≤ 24 h at the time of enrolment. Eligible patients will be stratified according to admission diagnosis (180 tetanus, 420 non-tetanus) and site and will be randomised in a 1:1 ratio to receive either (1) automated, continuous control of endotracheal cuff pressure or (2) intermittent measurement and control of endotracheal cuff pressure using a manual cuff pressure meter. The primary outcome is the occurrence of VARI, defined as either VAP or VAT during the ICU admission up to a maximum of 90 days after randomisation. Patients in both groups who are at risk for VARI will receive a standardised battery of investigations if their treating physician feels a new infection has occurred, the results of which will be used by an endpoint review committee, blinded to the allocated arm and independent of patient care, to determine the primary outcome. All enrolled patients will be followed for mortality and endotracheal tube cuff-related complications at 28 days and 90 days after randomisation. Other secondary outcomes include antibiotic use; days ventilated, in ICU and in hospital; inpatient mortality; costs of antibiotics in ICU; duration of ICU stay; and duration of hospital stay.DiscussionThis study will provide high-quality evidence concerning the use of continuous endotracheal cuff pressure control as a method to reduce VARI, antibiotic use and hospitalisation costs and to shorten stay.Trial registrationClinicalTrials.gov, NCT02966392. Registered on November 9, 2016. Protocol version: 2.0; issue date March 3, 2017.