Han-Chung Hu

Prediction of fluid responsiveness in acute respiratory distress syndrome patients ventilated with low tidal volume and high positive end-expiratory pressure*

Objective:Dynamic preload indicators with pulse pressure variation and stroke volume variation are superior to static indicators for predicting fluid responsiveness in mechanically ventilated patients. However, they are influenced by tidal volume and the level of positive end-expiratory pressure. The present study was designed to evaluate the clinical applicability of pulse pressure variation and stroke volume variation in predicting fluid responsiveness on acute respiratory distress syndrome patients ventilated with protective strategy (low tidal volume and high positive end-expiratory pressure). Design:Prospective, observational study. Setting:A 20-bed medical intensive care unit of a tertiary medical center. Patients:Twenty-two sedated and paralyzed early acute respiratory distress syndrome patients. Interventions:After being enrolled, central venous pressure, pulmonary capillary wedge pressure, and cardiac output index were obtained from a pulmonary artery catheter (OptiQ SvO2/CCO catheter), and intrathoracic blood volume, global end-diastolic volume, stroke volume variation, and pulse pressure variation were recorded from a PiCCOplus monitor. The whole set of hemodynamic measurements was performed before and after volume expansion with 500 mL hydroxyethyl starch (10% pentastarch 200/0.5). Measurements and Main Results:Cardiac output index, central venous pressure, pulmonary capillary wedge pressure, global end-diastolic volume, and intrathoracic blood volume significantly increased, and pulse pressure variation and stroke volume variation significantly decreased after volume expansion. Baseline pulse pressure variation significantly correlated with volume expansion-induced absolute changes (r = .62), or percent changes in cardiac output index (r = .75) after volume expansion. The area under the receiver operating characteristic curve was the highest for pulse pressure variation (area under the receiver operating characteristic curve = 0.768) than other indicators. The threshold value for baseline pulse pressure variation greater than 11.8% predicted a significant positive response to volume expansion with a sensitivity of 68% and a specificity of 100%. Conclusions:Baseline pulse pressure variation accurately predicted the fluid responsiveness in early acute respiratory distress syndrome patients. Roughly, a baseline pulse pressure variation greater than the threshold value of 12% is associated with a significant increase in cardiac output index after the end of volume expansion.

Diffuse alveolar damage associated mortality in selected acute respiratory distress syndrome patients with open lung biopsy

IntroductionDiffuse alveolar damage (DAD) is the pathological hallmark of acute respiratory distress syndrome (ARDS), however, the presence of DAD in the clinical criteria of ARDS patients by Berlin definition is little known. This study is designed to investigate the role of DAD in ARDS patients who underwent open lung biopsy.MethodsWe retrospectively reviewed all ARDS patients who met the Berlin definition and underwent open lung biopsy from January 1999 to January 2014 in a referred medical center. DAD is characterized by hyaline membrane formation, lung edema, inflammation, hemorrhage and alveolar epithelial cell injury. Clinical data including baseline characteristics, severity of ARDS, clinical and pathological diagnoses, and survival outcomes were analyzed.ResultsA total of 1838 patients with ARDS were identified and open lung biopsies were performed on 101 patients (5.5 %) during the study period. Of these 101 patients, the severity of ARDS on diagnosis was mild of 16.8 %, moderate of 56.5 % and severe of 26.7 %. The hospital mortality rate was not significant difference between the three groups (64.7 % vs 61.4 % vs 55.6 %, p = 0.81). Of the 101 clinical ARDS patients with open lung biopsies, 56.4 % (57/101) patients had DAD according to biopsy results. The proportion of DAD were 76.5 % (13/17) in mild, 56.1 % (32/57) in moderate and 44.4 % (12/27) in severe ARDS and there is no significant difference between the three groups (p = 0.113). Pathological findings of DAD patients had a higher hospital mortality rate than non-DAD patients (71.9 % vs 45.5 %, p = 0.007). Pathological findings of DAD (odds ratio: 3.554, 95 % CI, 1.385–9.12; p = 0.008) and Sequential Organ Failure Assessment score on the biopsy day (odds ratio: 1.424, 95 % CI, 1.187–1.707; p<0.001) were significantly and independently associated with hospital mortality. The baseline demographics and clinical characteristics were not significantly different between DAD and non-DAD patients.ConclusionsThe correlation of pathological findings of DAD and ARDS diagnosed by Berlin definition is modest. A pathological finding of DAD in ARDS patients is associated with hospital mortality and there are no clinical characteristics that could identify DAD patients before open lung biopsy.

The 23-valent pneumococcal polysaccharide vaccine is effective in elderly adults over 75 years old—Taiwan's PPV vaccination program

BACKGROUND Pneumococcal infection is a serious cause of mortality and morbidity in the elderly. A nationwide pneumococcal polysaccharide vaccine (PPV) program for elderly adults aged 75 years and older was conducted in Taiwan in 2008. The efficacy of the PPV in this very elderly population was evaluated. METHODS The data were analyzed using the Taiwan National Health Insurance Research Database (NHIRD), the cause-of-death registration database and the invasive pneumococcal disease (IPD) notification database of Taiwans Ministry of Health and Welfare. The efficacy of PPV administration in this very elderly population was evaluated using multivariate logistic regression after propensity score matching (PSM). The rates of IPD, death from IPD, pneumonia hospitalization, death from pneumonia, and all-cause mortality were compared for those who did and did not receive the PPV. RESULTS Among the 1078,955 eligible people, 318,257 (29.5%) received the PPV, and 760,698 (70.5%) were not vaccinated. Using PSM to adjust for confounding factors, including age, gender, influenza vaccination status, associated chronic diseases and health care utilization, those who received the PPV had significantly lower odds ratios (ORs) for IPD (OR=0.24, 95% CI=0.123-0.461, p<0.001), death from IPD (OR=0.09, 95% CI=0.011-0.704, p<0.022, p<0.001), pneumonia hospitalization (OR=0.40, 95% CI=0.395-0.415, p<0.001), death from pneumonia (OR=0.07, 95% CI=0.059-0.082, p<0.001), and all-cause mortality (OR=0.07, 95% CI=0.069-0.072, p<0.001) compared with those who were not vaccinated. CONCLUSIONS PPV vaccination in the previous year was associated with a 60% reduction in pneumonia hospitalization, a 76% reduction in IPD, and a greater than 90% reduction in death from pneumonia, IPD and all causes among people over 75 years old in Taiwan. Data from subsequent years in Taiwan and similar populations elsewhere are needed to evaluate the contribution of underlying variations in the mortality rate and the confounding effects of prior disease severity to these findings.

Survival Predictors in Acute Respiratory Distress Syndrome With Extracorporeal Membrane Oxygenation

BACKGROUND Extracorporeal membrane oxygenation (ECMO) can be used as a salvage therapy, but the effectiveness is controversial. The aim of this study was to investigate the predictors of mortality and the influence of organ dysfunction scores in severe acute respiratory distress syndrome (ARDS) patients treated with ECMO. METHODS The records of adult severe ARDS patients receiving ECMO support from May 2006 to December 2011 at Chang Gung Memorial Hospital were retrospectively analyzed. RESULTS The records of 65 patients with severe ARDS who received venovenous ECMO were analyzed. The hospital survival rate was 47.7%. Survivors were younger than nonsurvivors (41.4 ± 15.4 versus 54.1 ± 16.9 years, respectively; p = 0.002) and had shorter duration of mechanical ventilation before ECMO (52.7 ± 51.1 versus 112.1 ± 101.0 hours, respectively; p = 0.01). Before ECMO, Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and Multiple Organ Dysfunction scores were significantly lower for survivors than for nonsurvivors. Mortality rate increased with rising predictive score. During 7 days of ECMO use, organ dysfunction scores were significantly lower for survivors than nonsurvivors. CONCLUSIONS Severe ARDS patients who are younger, have shorter duration of mechanical ventilation, and lower organ dysfunction scores before ECMO initiation have more favorable survival outcome. Early application of ECMO, especially if predictive score is below 2, may improve survival. Organ dysfunction scores before and during ECMO support are correlated with survival.

Molecular evolution and the global reemergence of enterovirus D68 by genome-wide analysis

Abstract Human enterovirus D68 (EV-D68) was first reported in the United States in 1962; thereafter, a few cases were reported from 1970 to 2005, but 2 outbreaks occurred in the Philippines (2008) and the United States (2014). However, little is known regarding the molecular evolution of this globally reemerging virus due to a lack of whole-genome sequences and analyses. Here, all publically available sequences including 147 full and 1248 partial genomes from GenBank were collected and compared at the clade and subclade level; 11 whole genomes isolated in Taiwan (TW) in 2014 were also added to the database. Phylogenetic trees were constructed to identify a new subclade, B3, and represent clade circulations among strains. Nucleotide sequence identities of the VP1 gene were 94% to 95% based on a comparison of subclade B3 to B1 and B2 and 87% to 91% when comparing A, C, and D. The patterns of clade circulation need to be clarified to improve global monitoring of EV-D68, even though this virus showed lower diversity among clades compared with the common enterovirus EV-71. Notably, severe cases isolated from Taiwan and China in 2014 were found in subclade B3. One severe case from Taiwan occurred in a female patient with underlying angioimmunoblastic T-cell lymphoma, from whom a bronchoalveolar lavage specimen was obtained. Although host factors play a key role in disease severity, we cannot exclude the possibility that EV-D68 may trigger clinical symptoms or death. To further investigate the genetic diversity of EV-D68, we reported 34 amino acid (aa) polymorphisms identified by comparing subclade B3 to B1 and B2. Clade D strains had a 1-aa deletion and a 2-aa insertion in the VP1 gene, and 1 of our TW/2014 strains had a shorter deletion in the 5′ untranslated region than a previously reported deletion. In summary, a new subclade, genetic indels, and polymorphisms in global strains were discovered elucidating evolutionary and epidemiological trends of EV-D68, and 11 genomes were added to the database. Virus variants may contribute to disease severity and clinical manifestations, and further studies are needed to investigate the associations between genetic diversity and clinical outcomes.

Delayed Suspicion, Treatment and Isolation of Tuberculosis Patients in Pulmonology/ Infectious Diseases and Non-Pulmonology/ Infectious Diseases Wards

Background/Purpose Delayed diagnosis and isolation increases the risk of nosocomial transmission of tuberculosis (TB). To assess the risk of delayed management of TB, we analyzed the risk factors of prolonged delay in isolation of smear-positive TB patients in pulmonology/infectious diseases and other wards in a tertiary teaching hospital. Methods We enrolled smear-positive TB patients aged > 16 years with delayed respiratory isolation following hospitalization. Medical records were reviewed retrospectively. Time intervals between admission, order of sputum acid-fast staining, initiation of anti-tuberculous treatment and isolation were compared between pulmonology/infectious diseases wards (PIWs) and other wards. Risk factors were analyzed in patients with prolonged isolation delay of > 7 days in individual groups. Results Isolation was delayed in 191 (73.7%) of 259 hospitalized smear-positive TB patients. Median suspicion, treatment and isolation delays were 0, 3 and 4 days in PIWs and 1, 5 and 7 days in other wards. For patients admitted to non-PIWs, atypical chest radiographs, symptoms without dyspnea or not being admitted from the emergency department (ED) were risk factors for prolonged isolation delay exceeding 7 days. The only risk factor for delayed isolation in patients admitted to PIWs was age ≥ 70 years. Conclusion Delays in suspicion, treatment and isolation of TB patients were longer in non-PIWs. Clinicians should be alert to those admitted to non-PIWs with atypical chest radiographs, atypical symptoms, or not admitted from the ED.

Procalcitonin and C-reactive protein cannot differentiate bacterial or viral infection in COPD exacerbation requiring emergency department visits

Background Viral and bacterial infections are the most common causes of chronic obstructive pulmonary disease (COPD) exacerbations. Whether serum inflammatory markers can differentiate bacterial from virus infection in patients with COPD exacerbation requiring emergency department (ED) visits remains controversial. Methods Viral culture and polymerase chain reaction (PCR) were used to identify the viruses in the oropharynx of patients with COPD exacerbations. The bacteria were identified by the semiquantitative culture of the expectorated sputum. The peripheral blood white blood cell (WBC) counts, serum C-reactive protein (CRP), procalcitonin (PCT), and clinical symptoms were compared among patients with different types of infections. Results Viruses were isolated from 16 (22.2%) of the 72 patients enrolled. The most commonly identified viruses were parainfluenza type 3, influenza A, and rhinovirus. A total of 30 (41.7%) patients had positive bacterial cultures, with the most commonly found bacteria being Haemophilus influenzae and Haemophilus parainfluenzae. Five patients (6.9%) had both positive sputum cultures and virus identification. The WBC, CRP, and PCT levels of the bacteria-positive and bacteria-negative groups were not statistically different. Multivariate analysis showed that patients with increased sputum volumes during the COPD exacerbations had higher risks of recurrent exacerbations in the 1-year period following the first exacerbation. Conclusion WBC, CRP, or PCT could not differentiate between bacterial and viral infections in patients with COPD exacerbation requiring ED visits. Those with increased sputum during a COPD exacerbation had higher risks for recurrent exacerbations.

Renal replacement therapy in prolonged mechanical ventilation patients with renal failure in Taiwan

BACKGROUND Renal failure requiring renal replacement therapy (RRT) is associated with a high mortality rate in intensive care unit (ICU) patients. Little information is available on the outcomes of patients having prolonged mechanical ventilation (PMV) in addition to RRT. The purpose of this study was to investigate the impact of RRT in PMV patients. METHODS This was an observational, retrospective study in the 24-bed respiratory care center (RCC) of Chang Gung Memorial Hospital, Taiwan, between May 2001 and April 2007. The end points were weaning rate and survival rate at the RCC. RESULTS Of the 1301 RCC patients, 157 patients (13.7%) underwent RRT. The RRT patients had lower successful weaning rate (39.5% vs 58.4%, P < .001) and RCC survival rate (45.9% vs 71.9%, P < .001) compared with without-RRT patients. The successful weaning rates of end-stage renal disease (ESRD) patients, patients with RRT initiated at the ICU and continued at RCC, and patients whose RRT was initiated at the RCC were 49.2%, 39.1%, and 22.2%, respectively. The RCC survival rates were 50.8%, 47.8%, and 29.6%, respectively. The odds ratios of successful weaning rate and survival rate were 0.295 (95% confidence interval, 0.105-0.833; P = .021) and 0.407 (95% confidence interval, 0.155-1.021; P = .069) for patients whose RRT was initiated at the RCC vs ESRD patients. CONCLUSION The present study demonstrates that the need for RRT had a negative impact on weaning and mortality in PMV patients compared with patients without RRT. Patients who had RRT initiated at the RCC had a significantly lower weaning rate compared with ESRD patients.

Risk Factors of Methicillin-Resistant Staphylococcus aureus Infection and Correlation With Nasal Colonization Based on Molecular Genotyping in Medical Intensive Care Units: A Prospective Observational Study.

AbstractMethicillin-resistant Staphylococcus aureus (MRSA) is a common and important cause of colonization and infection in medical intensive care units (ICU). The aim of this study was to assess association factors between MRSA nasal colonization and subsequent infections in medical ICU patients by clinical investigation and molecular genotyping.A prospective cohort observational analysis of consecutive patients admitted to medical ICUs between November 2008 and May 2010 at a tertiary teaching hospital were included. To detect MRSA colonization, the specimens from the nares were obtained within 3 days of admission to the ICU and again 1 week following admission to the ICU. Genetic relatedness for colonized and clinical isolates from each study patient with MRSA infection were analyzed and compared.A total of 1266 patients were enrolled after excluding 195 patients with already present MRSA infections. Subsequent MRSA infection rates were higher in patients with nasal colonization than in those without (39.1% versus 14.7%, respectively). Multivariate Poisson regression analysis demonstrated that nasal MRSA colonization (relative risk [RR]: 2.50; 95% confidence interval [CI]: 1.90–3.27; P < 0.001) was independent predictors for subsequent MRSA infections. History of tracheostomy, however, was a protective predictor in all patients (RR: 0.38; 95% CI: 0.18–0.79; P = 0.010) and in patients with MRSA nasal colonization (RR: 0.22; 95% CI: 0.55–0.91; P = 0.037). Molecular genetics studies revealed that most MRSA isolates were healthcare-associated clones and that nasal and clinical isolates exhibited up to 75% shared identity.Methicillin-resistant S. aureus nasal colonization was significantly associated with subsequent MRSA infection among medical ICU patients. Previous MRSA infection was associated with subsequent MRSA infections, and history of tracheostomy associated with reducing this risk. Most MRSA isolates were healthcare-associated strains that were significantly correlated between nasal and clinical isolates.

Invasive fungal infection among hematopoietic stem cell transplantation patients with mechanical ventilation in the intensive care unit

BackgroundInvasive fungal infection (IFI) is associated with high morbidity and high mortality in hematopoietic stem cell transplantation (HSCT) patientsThe purpose of this study was to assess the characteristics and outcomes of HSCT patients with IFIs who are undergoing MV at a single institution in Taiwan.MethodsWe performed an observational retrospective analysis of IFIs in HSCT patients undergoing mechanical ventilation (MV) in an intensive care unit (ICU) from the year 2000 to 2009. The characteristics of these HSCT patients and risk factors related to IFIs were evaluated. The status of discharge, length of ICU stay, date of death and cause of death were also recorded.ResultsThere were 326 HSCT patients at the Linkou Chang-Gung Memorial Hospital (Taipei, Taiwan) during the study period. Sixty of these patients (18%) were transferred to the ICU and placed on mechanical ventilators. A total of 20 of these 60 patients (33%) had IFIs. Multivariate analysis indicated that independent risk factors for IFI were admission to an ICU more than 40 days after HSCT, graft versus host disease (GVHD), and high dose corticosteroid (p < 0.01 for all). The overall ICU mortality rate was 88% (53 of 60 patients), and was not significantly different for patients with IFIs (85%) and those without IFIs (90%, p = 0.676).ConclusionThere was a high incidence of IFIs in HSCT patients requiring MV in the ICU in our study cohort. The independent risk factors for IFI are ICU admission more than 40 days after HSCT, GVHD, and use of high-dose corticosteroid.