Younsuck Koh

Evolution of Mortality over Time in Patients Receiving Mechanical Ventilation

RATIONALE Baseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear. OBJECTIVES To estimate whether mortality in mechanically ventilated patients has changed over time. METHODS Prospective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models. MEASUREMENTS AND MAIN RESULTS We included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied positive end-expiratory pressure (mean 4.2 cm H2O [SD = 3.8] in 1998 to 7.0 cm of H2O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80-0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67-0.92). CONCLUSIONS Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved. Clinical trials registered with www.clinicaltrials.gov (NCT01093482).

Diaphragm dysfunction assessed by ultrasonography: influence on weaning from mechanical ventilation.

Objective:To determine the prevalence of diaphragmatic dysfunction diagnosed by M-mode ultrasonography (vertical excursion <10 mm or paradoxic movements) in medical intensive care unit patients and to assess the influence of diaphragmatic dysfunction on weaning outcome. Design:Prospective, observational study. Setting:Twenty-eight-bed medical intensive care unit in a university-affiliated hospital. Patients:Eighty-eight consecutive patients in the medical intensive care unit who required mechanical ventilation over 48 hrs and met the criteria for a spontaneous breathing trial were assessed. Patients with a history of diaphragmatic or neuromuscular disease or evidence of pneumothorax or pneumomediastinum were excluded. Interventions:During spontaneous breathing trial, each hemidiaphragm was evaluated by M-mode ultrasonography using the liver and spleen as windows with the patient supine. Rapid shallow breathing index was simultaneously calculated at the bedside. Measurements and Main Results:The prevalence of ultrasonographic diaphragmatic dysfunction among the eligible 82 patients was 29% (n = 24). Patients with diaphragmatic dysfunction had longer weaning time (401 [range, 226–612] hrs vs. 90 [range, 24–309] hrs, p < .01) and total ventilation time (576 [range, 374–850] hrs vs. 203 [range, 109–408] hrs, p < .01) than patients without diaphragmatic dysfunction. Patients with diaphragmatic dysfunction also had higher rates of primary (20 of 24 vs. 34 of 58, p < .01) and secondary (ten of 20 vs. ten of 46, p = .01) weaning failures than patients without diaphragmatic dysfunction. The area under the receiver operating characteristics curve of ultrasonographic criteria in predicting weaning failure was similar to that of rapid shallow breathing index. Conclusions:Using M-mode ultrasonography, diaphragmatic dysfunction was found in a substantial number of medical intensive care unit patients without histories of diaphragmatic disease. Patients with such diaphragmatic dysfunction showed frequent early and delayed weaning failures. Ultrasonography of the diaphragm may be useful in identifying patients at high risk of difficulty weaning.

Viral Infection in Patients with Severe Pneumonia Requiring Intensive Care Unit Admission

RATIONALE The role of viruses in pneumonia in adults and the impact of viral infection on mortality have not been elucidated. Previous studies have significant limitations in that they relied predominantly on upper respiratory specimens. OBJECTIVES To investigate the role of viral infection in adult patients with pneumonia requiring intensive care unit (ICU) admission. METHODS A retrospective analysis of a prospective cohort was conducted in a 28-bed medical ICU. Patients with severe community-acquired pneumonia (CAP) or healthcare-associated pneumonia (HCAP) were included in the study. MEASUREMENTS AND MAIN RESULTS A total of 198 patients (64 with CAP, 134 with HCAP) were included for analysis. Of these, 115 patients (58.1%) underwent bronchoscopic bronchoalveolar lavage (BAL), 104 of whom were tested for respiratory viruses by BAL fluid reverse-transcription polymerase chain reaction (RT-PCR). Nasopharyngeal specimen RT-PCR was performed in 159 patients (84.1%). Seventy-one patients (35.9%) had a bacterial infection, and 72 patients (36.4%) had a viral infection. Rhinovirus was the most common identified virus (23.6%), followed by parainfluenza virus (20.8%), human metapneumovirus (18.1%), influenza virus (16.7%), and respiratory syncytial virus (13.9%). Respiratory syncytial virus was significantly more common in the CAP group (CAP, 10.9%; HCAP, 2.2%; P = 0.01). The mortalities of patients with bacterial infections, viral infections, and bacterial-viral coinfections were not significantly different (25.5, 26.5, and 33.3%, respectively; P = 0.82). CONCLUSIONS Viruses are frequently found in the airway of patients with pneumonia requiring ICU admission and may cause severe forms of pneumonia. Patients with viral infection and bacterial infection had comparable mortality rates.

Effect of alveolar recruitment maneuver in early acute respiratory distress syndrome according to antiderecruitment strategy, etiological category of diffuse lung injury, and body position of the patient.

ObjectiveTo assess how the level of positive end-expiratory pressure (PEEP) (antiderecruitment strategy), etiological category of diffuse lung injury, and body position of the patient modify the effect of the alveolar recruitment maneuver (ARM) in acute respiratory distress syndrome (ARDS). DesignProspective clinical trial. SettingMedical intensive care unit at a tertiary hospital. PatientsForty-seven patients with early ARDS, including 19 patients from our preliminary study. InterventionFrom baseline ventilation at a tidal volume of 8 mL/kg and PEEP of 10 cm H2O, the ARM (a stepwise increase in the level of PEEP up to 30 cm H2O with a concomitant decrease in the magnitude of tidal volume down to 2 mL/kg) was given with (ARM + PEEP, n = 20) or without (ARM only, n = 19) subsequent increase of PEEP to 15 cm H2O. In eight other patients, PEEP was increased to 15 cm H2O without a preceding ARM (PEEP only). Measurements and ResultsIn all three groups, Pao2 was increased by the respective intervention (all p < .05). In the ARM-only group, Pao2 at 15 mins after intervention was lower than Pao2 immediate after intervention (p = .046). In the ARM + PEEP group, no such decrease in Pao2 was observed, and Pao2 at 15, 30, 45, and 60 mins after intervention was higher than in the ARM-only group (all p < .05). Compared with the PEEP-only group, Pao2 of the ARM + PEEP group was higher immediately after intervention and at the later time points (all p < .05). Compared with patients with ARDS associated with direct lung injury (pulmonary ARDS), patients with ARDS associated with indirect lung injury (extrapulmonary ARDS) showed a greater increase in Pao2 (27 ± 21% vs. 130 ± 112%;p = .002) and a greater decrease in radiologic scores (1.0 ± 2.4 vs. 3.4 ± 1.5;p = .005) after the ARM. The increase in Pao2 induced by the ARM was greater for patients in the supine position than for patients in the prone position (61 ± 82% vs. 21 ± 14%;p = .028). Consequently, Pao2 immediately after the ARM was similar in the two groups of patients in different positions. ConclusionsAfter the ARM, a sufficient level of PEEP is required as an antiderecruitment strategy. Pulmonary ARDS and extrapulmonary ARDS may be different pathophysiologic entities. An effective ARM may obviate the need for the prone position in ARDS at least in terms of oxygenation.

Corticosteroid treatment in critically ill patients with pandemic influenza A/H1N1 2009 infection: analytic strategy using propensity scores.

RATIONALE Administration of adjuvant corticosteroids to patients with pandemic influenza A/H1N1 2009 (pH1N1) may reduce inflammation and improve outcomes. OBJECTIVES To assess the effect of adjuvant corticosteroid treatment on the outcome of critically ill patients with pH1N1 infection. METHODS All adult patients with confirmed pH1N1 admitted to the intensive care unit of 28 hospitals in South Korea from September 2009 to February 2010 were enrolled. Patients with and without adjuvant corticosteroid treatment were retrospectively compared by two risk stratification models: (1) a retrospective cohort study that used propensity score analysis to adjust for confounding by treatment assignment and (2) a propensity-matched case-control study. MEASUREMENTS AND MAIN RESULTS A total of 245 patients were enrolled in the cohort study, 107 of whom (44%) received adjuvant steroid treatment. In the cohort study, the 90-day mortality rate of patients given steroids (58%, 62 of 107) was significantly higher than that of those not given steroids (27%, 37 of 138) (P < 0.001). The steroid group was more likely to have superinfection such as secondary bacterial pneumonia or invasive fungal infection, and had more prolonged intensive care unit stays than the no-steroid group. Multivariate analysis indicated that steroid treatment was associated with increased 90-day mortality when independent predictors for 90-day mortality and propensity score were considered (adjusted odds ratio, 2.20; 95% confidence interval, 1.03-4.71). In the case-control study, the 90-day mortality rate in the steroid group was 54% (35 of 65) and 31% (20 of 65) in the no-steroid group (McNemar test, P = 0.004). CONCLUSIONS Adjuvant corticosteroids were significantly associated with higher mortality in critically ill patients with pH1N1 infection.

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.

Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study

IntroductionFever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness.MethodsWe designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring > 48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAXICU) and the use of antipyretic treatments with 28-day mortality.ResultsWe recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P = 0.028, acetaminophen: 2.05, P = 0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P = 0.15, acetaminophen: 0.58, P = 0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAXICU 36.5°C to 37.4°C), MAXICU ≥ 39.5°C increased risk of 28-day mortality in septic patients (adjusted odds ratio 8.14, P = 0.01), but not in non-septic patients (adjusted odds ratio 0.47, P = 0.11).ConclusionsIn non-septic patients, high fever (≥ 39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis.Trial registrationClinicalTrials.gov: NCT00940654

Mechanistic scheme and effect of "extended sigh" as a recruitment maneuver in patients with acute respiratory distress syndrome: a preliminary study.

Objective To devise a new form of sigh (“extended sigh”) capable of providing a sufficient recruiting pressure × time, and to test it as a recruitment maneuver in patients with acute respiratory distress syndrome. Design Prospective uncontrolled clinical trial. Setting Medical intensive care unit of a university-affiliated hospital. Patients Twenty consecutive patients diagnosed with acute respiratory distress syndrome (18 men, 2 women, age 59 ± 10 yrs). Interventions From baseline settings of tidal volume (Vt) 8 mL/kg and positive end-expiratory pressure (PEEP) 10 cm H2O on volume control mode with the high pressure limit at 40 cm H2O, the Vt-PEEP values were changed to 6–15, 4–20, and 2–25, each step being 30 secs (inflation phase). After Vt-PEEP 2–25, the mode was switched to continuous positive airway pressure of 30 cm H2O for a duration of 30 secs (pause), after which the baseline setting was resumed following the reverse sequence of inflation (deflation phase). This extended sigh was performed twice with 1 min of baseline ventilation between. Measurements and Results Airway pressures and hemodynamic parameters were traced at each step during the extended sigh. Arterial blood gases and physiologic parameters were determined before the extended sigh (pre-extended sigh), at 5 mins after two extended sighs (post-extended sigh), and then every 15 mins for 1 hr. In our average patient, the recruiting pressure × time of the inflation phase was estimated to be 32.8–35.4 cm H2O × 90 secs. Compared with the inflation phase, inspiratory pause pressure of the deflation phase was lower at Vt-PEEP 6–15 (28.9 ± 2.7 cm H2O vs. 27.3 ± 2.8 cm H2O) and 4–20 (31.8 ± 2.9 cm H2O vs. 31.1 ± 2.9 cm H2O; both p < .05). Compared with pre-extended sigh, Pao2 (81.5 ± 15.3 mm Hg vs. 104.8 ± 25.0 mm Hg;p < .001) and static respiratory compliance both increased post-extended sigh (27.9 ± 7.9 mL/cm H2O vs. 30.2 ± 9.7 mL/cm H2O;p = .009). Improvement in these parameters was sustained above pre-extended sigh for the duration of the study. Major hemodynamic or respiratory complications were not noted during the study. Conclusion We present a new form of sigh (i.e., extended sigh) capable of achieving an augmented recruiting pressure × time through a prolonged inflation on a gradually increased end-expiratory pressure. In view of the sustained effect and absence of major complications in our patients, extended sigh could be a useful recruitment maneuver in acute respiratory distress syndrome.

Characteristics of lung cancer in Korea, 1997

The high proportion of smokers and the incidence of advanced, unresectable lung cancer in Korea were examined to aid the development of a national anti-smoking program and the early detection of lung cancer. Koreans are a single racial group with a high smoking rate among men and a contrastingly low smoking rate among women. This report documents a retrospective investigation conducted by The Korean Academy of Tuberculosis and Respiratory Disease into the characteristics of all lung cancers diagnosed between 1 January 1997 and 31 December 1997 in Korea. Among the 3794 patients included in this study, 76.8% were smokers and, in particular, 89.8% of the males were smokers. Squamous cell carcinoma was the most frequent type of lung cancer encountered (44.7%), followed by adenocarcinoma (27.9%). The smoking rate in the case of adenocarcinoma was significantly lower than that found in both squamous cell carcinoma and small cell cancer. The most common symptom was a cough. Only 7.2% of patients were asymptomatic. Bronchoscopic biopsy has a primary role in the diagnosis of squamous cell carcinoma and small cell cancer, but percutaneous needle biopsy has a more important role in the case of adenocarcinoma. Two-thirds of the nonsmall cell lung cancer patients were detected in the unresectable advanced stages (IIIB and IV). In contrast to other countries, squamous cell carcinoma is still the most frequent type of lung cancer in Korea. The high proportion of smokers and the incidence of advanced, unresectable lung cancer at diagnosis have urged development of a national anti-smoking program to promote the cessation of smoking and the early detection of lung cancer.

Clinical course and lung function change of idiopathic nonspecific interstitial pneumonia

Most studies of idiopathic nonspecific interstitial pneumonia (NSIP) have primarily studied mortality. In order to clarify the detailed outcome and prognostic markers in idiopathic NSIP, the clinical course with initial radiological and clinical features was analysed. The clinical course of 83 patients who were classified with idiopathic NSIP (72 fibrotic, 11 cellular; 27 males and 56 females; mean±sd age 54.4±10.1 yrs) was retrospectively analysed. In fibrotic NSIP, 16 (22%) patients died of NSIP-related causes with a median (range) follow-up of 53 (0.3–181) months. Despite the favourable survival (5-yr 74%), patients with fibrotic NSIP were frequently hospitalised with recurrence rate of 36%. Reduced forced vital capacity at 12 months was a predictor of mortality. On follow-up, lung function was improved or stable in ∼80% of the patients. The extent of consolidation and ground-glass opacity on initial high-resolution computed tomography correlated significantly with serial changes of lung function, and the presence of honeycombing was a predictor of poor prognosis. During follow-up, eight (10%) patients developed collagen vascular disease. In conclusion, the overall prognosis of fibrotic nonspecific interstitial pneumonia was good; however, there were significant recurrences despite initial improvement and a subset of the patients did not respond to therapy. Some patients developed collagen vascular diseases at a later date.