Liberation from Mechanical Ventilation in Critically Ill Patients: Korean Society of Critical Care Medicine Clinical Practice Guidelines.

BACKGROUND: Successful liberation from mechanical ventilation is one of the most crucial processes in critical care because it is the first step by which a respiratory failure patient begins to transition out of the intensive care unit and return to their own life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider not only the individual experiences of healthcare professionals, but also scientific and systematic approaches. Recently, numerous studies have investigated methods and tools for identifying when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians about liberation from the ventilator. METHOD: Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. Those evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved recommendations. RESULT: Recommendations for nine population, intervention, comparator, outcome (PICO) questions about ventilator liberation are presented in this document. This guideline includes seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation. CONCLUSIONS: We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation.

Liberation from mechanical ventilation in critically ill patients: Korean Society of Critical Care Medicine Clinical Practice Guidelines.

BACKGROUND: Successful liberation from mechanical ventilation is one of the most crucial processes in critical care because it is the first step by which a respiratory failure patient begins to transition out of the intensive care unit and return to their own life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider not only the individual experiences of healthcare professionals, but also scientific and systematic approaches. Recently, numerous studies have investigated methods and tools for identifying when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians about liberation from the ventilator. METHODS: Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. Those evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved recommendations. RESULTS: Recommendations for nine PICO (population, intervention, comparator, and outcome) questions about ventilator liberation are presented in this document. This guideline includes seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation. CONCLUSIONS: We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation.

The effects of environmental interventions for delirium in critically ill surgical patients.

BACKGROUND: Delirium occurs at high rates among patients in intensive care units and increases the risk of morbidity and mortality. The purpose of this study was to investigate the effects of environmental interventions on delirium. METHODS: This prospective cohort study enrolled 192 patients admitted to the surgical intensive care unit (SICU) during the pre-intervention (June 2013 to October 2013) and post-intervention (June 2014 to October 2014) periods. Environmental interventions involved a cognitive assessment, an orientation, and a comfortable environment including proper sleep conditions. The primary outcomes were the prevalence, duration, and onset of delirium. RESULTS: There were no statistically significant differences in incidence rate, time of delirium onset, general characteristics, and mortality between the pre-intervention and post-intervention groups. The durations of delirium were 14.4±19.1 and 7.7±7.3 days in the pre-intervention and post-intervention groups, respectively, a significant reduction (P=0.027). The lengths of SICU stay were 20.0±22.9 and 12.6±8.7 days for the pre-intervention and post-intervention groups, respectively, also a significant reduction (P=0.030). CONCLUSIONS: The implementation of an environmental intervention program reduced the duration of delirium and length of stay in the SICU for critically ill surgical patients.

Current status of laparoscopic emergency surgery in Korea: multicenter restrospective cohort study.

Purpose: Laparoscopic surgery is a choice in several emergency settings. However, there has been no nationwide study or survey that has compared the clinical use of laparoscopic emergency surgery (LES) versus open abdominal emergency surgery (OES) in Korea. Therefore, we examined the state of LES across multiple centers in Korea and further compared this data with the global state based on published reports. Methods: Data of 2,122 patients who received abdominal emergency surgery between 2014 and 2019 in three hospitals in Korea were collected and retrospectively analyzed. Several clinical factors were investigated and analyzed. Results: Of the patients, 1,280 (60.3%) were in the OES group and 842 (39.7%) were in the LES group. The most commonly operated organ in OES was the small bowel (25.8%), whereas that for LES was the appendix. In appendectomy and cholecystectomy, 93.7% and 88.0% were in the LES group. In small bowel surgery, gastric surgery, and large bowel surgery, 89.4%, 92.0%, and 79.1% were in the OES group. The severity-related factors of patient status demonstrated statistically significant limiting factors of selection between LES and OES. Conclusion: Although our study has several limitations, compared to the LES data from other countries, the general LES state was similar in appendectomies, cholecystectomies, and small bowel surgeries. However, in gastric and colorectal surgeries, the LES state was different from those of other countries. This study demonstrated the LES state and limiting factors of selection between LES and OES in various operated organs. Further studies are required to analyze these differences and the various limiting factors.

Risk factors for Pneumocystis pneumonia with acute respiratory failure among kidney transplant recipients.

PURPOSE: One of the rare life-threatening fungal infections is pneumocystis pneumonia (PCP). Immunocompromised patients are the main vulnerable population. We investigate the risk factors associated with the development of severe PCP infection with acute respiratory failure after kidney transplantation. MATERIALS AND METHODS: This is a retrospective, single-center, case-control study. PCP patients who are kidney transplant recipients and required high-flow oxygen support or mechanical ventilation between March 2009 and February 2017 were included in the study. The comparison was conducted between the non-severe and severe PCP groups. To identify associated risk factors, we performed univariate and multivariate logistic regression. RESULTS: Among the total 2,330 kidney transplant recipients, 50 patients (2.1%) were diagnosed with PCP. Of these, 27 patients (54.0%) had severe PCP and 7 patients (14.0%) died, all of them were severe PCP patients. In the severe PCP group, the time from transplantation to PCP diagnosis (23.4 ± 24.9 months vs. 13.7 ± 9.9 months, p = 0.090) was insignificantly faster than in the non-severe PCP group. According to multiple logistic regression analysis, the significant risk factors associated with severe PCP were as follows, age (odds ratios (OR) 1.07; 95% confidence intervals (CI): 1.01-1.13; p = 0.027), time from transplantation to PCP diagnosis (odds ratios (OR) 0.92; 95% confidence intervals (CI): 0.86-0.99; p = 0.024), lymphopenia (OR 6.48; 95% CI: 1.05-40.09; p = 0.044), and history of acute rejection within 1 year (OR 8.28; 95% CI: 1.29-53.20; p = 0.026). CONCLUSION: Patients who have lymphopenia at the time of hospital admission or have been recently treated with acute rejection are more likely to progress to severe PCP, requiring intensive monitoring and aggressive treatment.

Clinical outcomes and prognostic factors of patients with sepsis caused by intra-abdominal infection in the intensive care unit: a post-hoc analysis of a prospective cohort study in Korea.

BACKGROUND: Sepsis is the most common cause of death in hospitals, and intra-abdominal infection (IAI) accounts for a large portion of the causes of sepsis. We investigated the clinical outcomes and factors influencing mortality of patients with sepsis due to IAI. METHODS: This post-hoc analysis of a prospective cohort study included 2126 patients with sepsis who visited 16 tertiary care hospitals in Korea (September 2019-February 2020). The analysis included 219 patients aged > 19 years who were admitted to intensive care units owing to sepsis caused by IAI. RESULTS: The incidence of septic shock was 47% and was significantly higher in the non-survivor group (58.7% vs 42.3%, p = 0.028). The overall 28-day mortality was 28.8%. In multivariable logistic regression, after adjusting for age, sex, Charlson Comorbidity Index, and lactic acid, only coagulation dysfunction (odds ratio: 2.78 [1.47-5.23], p = 0.001) was independently associated, and after adjusting for each risk factor, only simplified acute physiology score III (SAPS 3) (p < 0.001) and continuous renal replacement therapy (CRRT) (p < 0.001) were independently associated with higher 28-day mortality. CONCLUSIONS: The SAPS 3 score and acute kidney injury with CRRT were independently associated with increased 28-day mortality. Additional support may be needed in patients with coagulopathy than in those with other organ dysfunctions due to IAI because patients with coagulopathy had worse prognosis.

Clinical Effect of Preoperative 25-OH-Vitamin D3 Level in Liver Transplant Recipients.

BACKGROUND: Vitamin D deficiency is common in patients with chronic liver disease and is associated with increased risk of infection and mortality. This study evaluated the effects of preoperative vitamin D levels on clinical outcomes after liver transplant. METHODS: This single-center retrospective study included liver transplant recipients from June to November 2017 who had preoperative 25-OH-vitamin D3 (25-OH-D3) data. Severe vitamin D deficiency, insufficiency, and normal levels were defined as serum 25-OH-D3 concentrations of < 10 ng/mL, 10 to 20 ng/mL, and ≥ 20 ng/mL, respectively. The primary outcome was length of hospital stay; secondary outcomes included the duration of normalization of inflammatory markers after liver transplant, new infection rates, rejection rates, length of intensive care unit stay, and mortality according to preoperative 25-OH-D3 levels. RESULTS: Among 219 liver transplant recipients, 67.6% were vitamin D-deficient. The mean (standard deviation) 25-OH-D3 concentration was 17.8 (13.2) ng/mL, and 65 (29.7%) patients had levels < 10 ng/mL. Patients with lower mean 25-OH-D3 levels had significantly longer intensive care unit (13.8 [21.9] days vs 5.9 [12.3] days vs 2.7 [4.6] days, P < .001) and hospital (59.0 [66.0] days vs 42.0 [67.4] days vs 27.2 [17.1] days, P = .001) stays. The incidence of new infections was higher in the vitamin D deficiency group. (46.2% vs 28.9% vs 14.1%, P < .001). A higher Nutritional Risk Screening 2002 score (adjusted odds ratio, 1.77; 95% confidence interval [CI], 1.24-2.56; P = .002) and severe vitamin D deficiency (adjusted odds ratio, 3.43; 95% CI, 1.57-7.57; P = .002) were significant risk factors for poor outcome among patients who had been in the hospital for more than 43 days. CONCLUSIONS: Vitamin D deficiency before liver transplant was associated with increased intensive care unit and hospital lengths of stay. Although several factors may influence the clinical outcomes of patients with liver transplant, low vitamin D3 was an independent risk factor.

2021 KSCCM clinical practice guidelines for pain, agitation, delirium, immobility, and sleep disturbance in the intensive care unit.

We revised and expanded the "2010 Guideline for the Use of Sedatives and Analgesics in the Adult Intensive Care Unit (ICU)." We revised the 2010 Guideline based mainly on the 2018 "Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption (PADIS) in Adult Patients in the ICU," which was an updated 2013 pain, agitation, and delirium guideline with the inclusion of two additional topics (rehabilitation/mobility and sleep). Since it was not possible to hold face-to-face meetings of panels due to the coronavirus disease 2019 (COVID-19) pandemic, all discussions took place via virtual conference platforms and e-mail with the participation of all panelists. All authors drafted the recommendations, and all panelists discussed and revised the recommendations several times. The quality of evidence for each recommendation was classified as high (level A), moderate (level B), or low/very low (level C), and all panelists voted on the quality level of each recommendation. The participating panelists had no conflicts of interest on related topics. The development of this guideline was independent of any industry funding. The Pain, Agitation/Sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep Disturbance panels issued 42 recommendations (level A, 6; level B, 18; and level C, 18). The 2021 clinical practice guideline provides up-to-date information on how to prevent and manage pain, agitation/sedation, delirium, immobility, and sleep disturbance in adult ICU patients. We believe that these guidelines can provide an integrated method for clinicians to manage PADIS in adult ICU patients.

Development of a new pharmacokinetic model for target-concentration controlled infusion of vancomycin in critically ill patients.

The aim of this prospective study was to construct a new pharmacokinetic model of vancomycin for target-concentration controlled infusion (TCI). As the first loading dose, 25 mg/kg of vancomycin was administered during 60-90 min. Arterial blood samples were obtained at pre-set intervals to measure the serum concentrations of vancomycin. Population pharmacokinetic analysis was performed using the NONMEM software (ICON Development Solutions). In total, 197 serum concentration measurements from 22 patients were used to characterise the pharmacokinetics of vancomycin. A three-compartment mammillary model best described the pharmacokinetics of vancomycin in critically ill patients. The ideal body weight was a significant covariate for the central and slow peripheral volume of distribution. The weight and age converted to categorical variables at a cut-off of 65 years were a significant covariate for the clearance. Based on the results of stochastic simulation, the TCI method maintained the therapeutic concentration range for the longest duration. In addition, assuming that vancomycin was administered by the TCI method for 7 days, the dose was reduced by about 15% compared with the standard administration methods. The daily area under the curve values were maintained between 500 mg·h/L and 600 mg·h/L. TCI has the potential to become a new infusion method for patient-tailored dosing in critically ill patients. To administer vancomycin via TCI in clinical practice, the newly constructed pharmacokinetic model should undergo proper external validation.

Impact of an Acute Care Surgery Model on the Management of Acute Appendicitis in South Korea: A Retrospective Cohort Study.

BACKGROUND: The acute care surgery (ACS) system is a new model for the prompt management of diseases that require rapid treatment in patients with acute abdomen. This study compared the outcomes and characteristics of the ACS system and traditional on-call system (TROS) for acute appendicitis in South Korea. METHODS: This single-center, retrospective study included all patients (aged ≥18 years) who underwent surgery for acute appendicitis in 2016 and 2018. The TROS and ACS system were used for the 2016 and 2018 groups, respectively. We retrospectively obtained data on each patient from the electrical medical records. The independent samples t-test and Mann-Whitney U-test were used for continuous and nonnormally distributed data, respectively. RESULTS: In total, 126 patients were included. The time taken to get from the emergency room admission to the operating room, operation times, and postoperative complication rates were similar between both groups. However, the length of the hospital stay was shorter in the ACS group than in the TROS group (4.3 ± 3.2 days vs. 7.2 ± 9.6 days, p=0.039). CONCLUSIONS: Since the introduction of the ACS system, the length of hospital stay for surgical patients has decreased. This may be due to the application of an integrated medical procedure, such as a new clinical pathway, rather than differences in the surgical techniques.

Comparison of Measured Energy Expenditure Using Indirect Calorimetry vs Predictive Equations for Liver Transplant Recipients.

BACKGROUND: To assess the appropriate energy expenditure requirement for liver transplant (LT) recipients in South Korea, 4 commonly used predictive equations were compared with indirect calorimetry (IC). METHODS: A prospective observational study was conducted in the surgical intensive care unit (ICU) of an academic tertiary hospital between December 2017 and September 2018. The study population comprised LT recipients expected to remain in the ICU >48 hours postoperatively. Resting energy expenditure (REE) was measured 48 hours after ICU admission using open-circuit IC. Theoretical REE was estimated using 4 predictive equations (simple weight-based equation [25 kcal/kg/day], Harris-Benedict, Ireton-Jones [ventilated], and Penn State 1988). Derived and measured REE values were compared using an intraclass correlation coefficient (ICC) and Bland-Altman plots. RESULTS: Of 50 patients screened, 46 were enrolled, were measured, and completed the study. The Penn State equation showed 65.0% agreement with IC (ICC, 0.65); the simple weight-based (25 kcal/kg/day), Harris-Benedict, and Ireton-Jones equations showed 62.0%, 56.0% and 39.0% agreement, respectively. Bland-Altman analysis showed that all 4 predictive equations had fixed bias, although the simple weight-based equation (25 kcal/kg/day) showed the least. CONCLUSION: Although predicted REE calculated using the Penn State method agreed with the measured REE, all 4 equations showed fixed bias and appeared to be inaccurate for predicting REE in LT recipients. Precise measurement using IC may be necessary when treating LT recipients to avoid underestimating or overestimating their metabolic needs.

Simplified Diagnosis of Critical Illness Polyneuropathy in Patients with Prolonged Mechanical Ventilation: A Prospective Observational Cohort Study.

BACKGROUND: Although early identification of critical illness polyneuropathy (CIP) is necessary, the established diagnostic criteria have several limitations in the intensive care unit (ICU) setting. The purpose of this study was to define simplified diagnostic criteria of CIP that best predict clinical outcomes. METHODS: This prospective, single-center study included 41 ICU patients with prolonged mechanical ventilation (≥21 days). We applied three different sets of diagnostic criteria (combining the results of the Medical Research Council (MRC) sum score and nerve conduction studies (NCS)) for CIP in order to identify the criteria with the best predictive power for clinical outcomes. RESULTS: The simplified diagnosis of CIP meeting the criteria, i.e., that the MRC sum score < 48 and amplitudes of the tibial and sural nerve < 80% of the lower limit of normal, showed the strongest association with 0 ventilator-free days at day 60 (odds ratio, 6.222; p = 0.029). CONCLUSIONS: The diagnostic criteria combining the MRC sum score and the tibial and the sural NCS were identified as the simplified criteria of CIP that best predicted the clinical outcomes. The implementation of these simplified criteria may allow for early identification of CIP in the ICU, thereby contributing to prompt interventions for patients with a poor prognosis.

Risk Factors of Bacteremia following Multiple Traumas.

BACKGROUND: Bacteremia is a major nosocomial infection that frequently occurs in trauma patients, increasing morbidity and mortality. The aim of this study was to identify risk factors and to describe epidemiological patterns for early onset (EOB) and late onset (LOB) bacteremia after trauma. METHODS: We retrospectively reviewed medical records of all trauma patients admitted to the surgical intensive care unit and general ward between January 2011 and December 2015. The information was collected for each patient and recorded in a computer database: early onset bacteremia (EOB) was defined as when onset occurred within 7 days after trauma, and late onset bacteremia (LOB) was defined as when onset occurred after 7 days from trauma. RESULTS: Thirty-four patients of 859 (4%) developed bacteremia during their hospital stay: 4 (11.8%) developed EOB, 26 (76.4%) LOB, and 4 (11.8%) patients developed both of them. Sixty events of bacteremia happened to these patients: 9 (15.0%) EOB and 51 (85.0%) LOB. Gram-positive cocci were isolated more frequently than Gram-negative bacilli in both groups. Gram-positive cocci were more frequently isolated in EOB than in LOB; otherwise, there was no statistical significance (77.8% vs. 64.7%, p=0.683). Central line-associated blood stream infection (CLABSI) and surgical site infection (SSI) were the most common identified source for LOB. Presence of liver (OR: 2.66, p=0.035) and pelvic injury (OR: 2.25, p=0.038), gastrointestinal tract perforation (OR: 5.48, p=0.002), and massive transfusion (OR: 3.36, p=0.006) represented risk factors for bacteremia. CONCLUSIONS: Presence of pelvic and liver injury on arrival in emergency department, gastrointestinal tract perforation, and massive transfusion within the first 24 hours after trauma appears to be significant risk factors for bacteremia.

The size of pelvic hematoma can be a predictive factor for angioembolization in hemodynamically unstable pelvic trauma.

PURPOSE: Unstable pelvic fracture with bleeding can be fatal, with a mortality rate of up to 40%. Therefore, early detection and treatment are important in unstable pelvic trauma. We investigated the early predictive factors for possible embolization in patients with hemodynamically unstable pelvic trauma. METHODS: From January 2011 to December 2013, 46 patients with shock arrived at a single hospital within 24 hours after injury. Of them, 44 patients underwent CT scan after initial resuscitation, except for 2 who were dead on arrival. Nine patients with other organ injuries were excluded. Seventeen patients underwent embolization. A single radiologist measured the width (longest length in axial view) and length (longest length in coronal view) of pelvic hematoma on CT scans. Demographic, clinical, and radiological data were reviewed retrospectively. RESULTS: Among 35 patients with hemodynamically unstable pelvic fracture, 22 (62.9%) were men. Width (P = 0.002) and length (P = 0.006) of hematoma on CT scans were significantly different between the embolization and nonembolization groups. The predictors of embolization were width of pelvic hematoma (odds ratio [OR], 1.07; P = 0.028) and female sex (OR, 10.83; P = 0.031). The cutoff value was 3.35 cm. More embolization was performed (OR, 12.00; P = 0.003) and higher mortality was observed in patients with hematoma width >3.35 cm (OR, 4.96; P = 0.048). CONCLUSION: Patients with hemodynamically unstable pelvic trauma have a high mortality rate. CT is useful for the initial identification of the need for embolization among these patients. The width of pelvic hematoma can predict possible embolization in patients with unstable pelvic trauma.

In vitro inhibition of Toxoplasma gondii by the anti-malarial candidate, 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol.

An anti-malarial candidate, 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251), was studied to characterize its potential as a novel anti-Toxoplasma gondii drug. In the present study, IC50 and LC50 of N-251 on host cells and T. gondii were compared to those of artemisinin and sulfadiazine. The IC50 on Huh-7 cells was 10.19µg/ml, 67.69µg/ml and 310.17µg/ml for N-251, artemisinin, and sulfadiazine, respectively. The LC50 for anti-T. gondii effect was shown to be 1.11µg/ml, 5.79µg/ml, and 5.45µg/ml for N-251, artemisinin and sulfadiazine, respectively. N-251 concentration causing complete parasiticidal effect with minimal cytotoxicity on host cells was determined to be 5µg/ml. Additionally, the anti-T. gondii effect of N-251 was confirmed by ultrastructural changes, loss of organelles, degenerated morphology and the increase of amylopectin as detected by transmission electron microscope (TEM). Accordingly, the present study suggests that the anti-malarial synthetic endoperoxide, N-251, is an emerging drug candidate more effective than artemisinin and sulfadiazine.

Depth profiling analysis of CuIn1-xGa(x)Se2 absorber layer by laser induced breakdown spectroscopy in atmospheric conditions.

This work reports the capability of depth profile analysis of thin CuIn1-xGa(x)Se2 (CIGS) absorber layer (1.89 µm) with a sub-hundred nanometer resolution by laser induced breakdown spectroscopy (LIBS). The LIBS analysis was carried out with a commercial CIGS solar cell on flexible substrate by using a pulsed Nd:YAG laser (λ = 532 nm, τ = 5 ns, top-hat profile) and an intensified charge-coupled device spectrometer in atmospheric conditions. The measured LIBS elemental profiles across the CIGS layer agreed closely to those measured by secondary ion mass spectrometry. The resolution of depth profile analysis was about 88 nm. Owing to the short measurement time of LIBS and the capability of in-air measurement, it is expected that LIBS can be applied for in situ analysis of elemental composition and their distribution across the film thickness during development and manufacturing of CIGS solar cells.