Early Treatment of High-Risk Hospitalized Coronavirus Disease 2019 (COVID-19) Patients With a Combination of Interferon Beta-1b and Remdesivir: A Phase 2 Open-label Randomized Controlled Trial.

BACKGROUND: Early antiviral therapy was effective in the treatment of coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients. METHODS: We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200 mg loading on day 1 followed by 100 mg daily on day 2 to 5 (combination group), or to remdesivir only of similar regimen (control group) (1:1). The primary endpoint was the time to complete alleviation of symptoms (NEWS2 = 0). RESULTS: Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom onset was 3 days. The median age was 65 years, and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary endpoint, the combination group was significantly quicker to NEWS2 = 0 (4 vs 6.5 days; hazard ratio [HR], 6.59; 95% confidence interval [CI], 6.1-7.09; P < .0001) when compared to the control group. For the secondary endpoints, the combination group was quicker to negative nasopharyngeal swab (NPS) viral load (VL) (6 vs 8 days; HR, 8.16; 95% CI, 7.79-8.52; P < .0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98-11.58; P < .0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9-8.6, P < .0001) was the most significant independent factor associated with NEWS2 = 0 on day 4. CONCLUSIONS: Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, and in shortening viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients. CLINICAL TRIALS REGISTRATION: NCT04647695.

NLR, MLR, PLR and RDW to predict outcome and differentiate between viral and bacterial pneumonia in the intensive care unit.

The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and red cell distribution width (RDW) are emerging biomarkers to predict outcomes in general ward patients. However, their role in the prognostication of critically ill patients with pneumonia is unclear. A total of 216 adult patients were enrolled over 2 years. They were classified into viral and bacterial pneumonia groups, as represented by influenza A virus and Streptococcus pneumoniae, respectively. Demographics, outcomes, and laboratory parameters were analysed. The prognostic power of blood parameters was determined by the respective area under the receiver operating characteristic curve (AUROC). Performance was compared using the APACHE IV score. Discriminant ability in differentiating viral and bacterial aetiologies was examined. Viral and bacterial pneumonia were identified in 111 and 105 patients, respectively. In predicting hospital mortality, the APACHE IV score was the best prognostic score compared with all blood parameters studied (AUC 0.769, 95% CI 0.705-0.833). In classification tree analysis, the most significant predictor of hospital mortality was the APACHE IV score (adjusted P = 0.000, χ2 = 35.591). Mechanical ventilation was associated with higher hospital mortality in patients with low APACHE IV scores ≤ 70 (adjusted P = 0.014, χ2 = 5.999). In patients with high APACHE IV scores > 90, age > 78 (adjusted P = 0.007, χ2 = 11.221) and thrombocytopaenia (platelet count ≤ 128, adjusted P = 0.004, χ2 = 12.316) were predictive of higher hospital mortality. The APACHE IV score is superior to all blood parameters studied in predicting hospital mortality. The single inflammatory marker with comparable prognostic performance to the APACHE IV score is platelet count at 48 h. However, there is no ideal biomarker for differentiating between viral and bacterial pneumonia.

An External Validation of Scoring Systems in Mortality Prediction in Veno-Venous Extracorporeal Membrane Oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) offers the last resort in the treatment of acute respiratory distress syndrome (ARDS). Various scoring systems have been established, yet external validation of these scoring systems in the Asian population remains scarce. We aim to identify factors associated with hospital mortality and to validate various scoring systems in the prediction of hospital mortality. A retrospective analysis of adults admitted to Pamela Youde Nethersole Eastern Hospital intensive care unit who received VV ECMO from January 1, 2010 to June 30, 2019 was performed. Demographics, ventilation strategies, rescue therapies, and clinical outcomes were compared. The primary outcome was hospital mortality and secondary outcomes were intensive care unit (ICU) mortality, ICU, and hospital length of stay. There were 122 VV ECMO performed for ARDS, of which 78 survived and 44 died. VV ECMO performed for viral pneumonitis was significantly associated with better survival (55.1% vs. 25%, p = 0.001) compared with other causes. As for prediction scores, the PREdiction of Survival on ECMO Therapy-Score had the highest area under receiver operator curve of 0.733 (95% confidence interval [CI]: 0.643-0.823), whereas that of PRedicting dEath for SEvere ARDS on VV ECMO score was 0.662 (95% CI: 0.561-0.764), Respiratory Extracorporeal Membrane Oxygenation Survival Prediction score was 0.657 (95% CI: 0.553-0.761), Sequential Organ Failure Assessment score was 0.652 (95% CI: 0.547-0.757), and VV ECMO mortality score was 0.637 (95% CI: 0.532-0.742). In our cohort, VV ECMO performed for viral pneumonitis was associated with a higher hospital survival. Prediction scores are helpful in our population and provide a useful reference to hospital mortality.

Effect of the underlying malignancy on critically ill septic patient's outcome.

BACKGROUND: Sepsis is an important cause of mortality and morbidity among critically ill patients with underlying malignancy. METHODS: Patients with sepsis admitted to the intensive care unit (ICU) of the Pamela Youde Nethersole Eastern Hospital from January 1, 2010 to April 30, 2019 were recruited. Demographics, laboratory parameter, and outcome were analyzed. Those with underlying malignancy were matched with those without malignancy based on their severity of organ failure (defined by the sequential organ failure assessment [SOFA] score) and septic source. RESULTS: Two hundred sixty-three patients with underlying active malignancy were matched with 259 patients without malignancy. Those with malignancy had higher APACHE IV score (89 vs. 83), lower albumin (22.1 vs. 24.4), neutrophil count (6.0 vs. 9.3), hemoglobin (8.0 vs. 9.8), platelet count (113 vs. 133), less use of mechanical ventilation (35.7% vs. 45.9%), renal replacement therapy (22.1% vs. 28.2%) and vasopressor (66.2% vs. 74.9%), higher 30-day (34.2% vs. 24.3%) ICU (22.4% vs. 18.9%), and 1-year (62.4% vs. 36.7%) mortality compared with those without malignancy. A higher APACHE IV score and pulmonary sepsis were predictors of 30-day mortality by Cox regression analysis. CONCLUSION: Disease severity and pulmonary sepsis, but not underlying malignancy, predicted short-term mortality among critically ill septic patients.

Critically ill patients with COVID-19 in Hong Kong: a multicentre retrospective observational cohort study

Objective: To report the first eight cases of critically ill patients with coronavirus disease 2019 (COVID-19) in Hong Kong, describing the treatments and supportive care they received and their 28-day outcomes. Design: Multicentre retrospective observational cohort study. Setting: Three multidisciplinary intensive care units (ICUs) in Hong Kong. Participants: All adult critically ill patients with confirmed COVID-19 admitted to ICUs in Hong Kong between 22 January and 11 February 2020. Main outcome measure: 28-day mortality. Results: Eight out of 49 patients with COVID-19 (16%) were admitted to Hong Kong ICUs during the study period. The median age was 64.5 years (range, 42­70) with a median admission Sequential Organ Failure Assessment (SOFA) score of 6 (IQR, 4­7). Six patients (75%) required mechanical ventilation, six patients (75%) required vasopressors and two (25%) required renal replacement therapy. None of the patients required prone ventilation, nitric oxide or extracorporeal membrane oxygenation. The median times to shock reversal and extubation were 9 and 11 days respectively. At 28 days, one patient (12%) had died and the remaining seven (88%) all survived to ICU discharge. Only one of the survivors (14%) still required oxygen at 28 days. Conclusion: Critically ill patients with COVID-19 often require a moderate duration of mechanical ventilation and vasopressor support. Most of these patients recover and survive to ICU discharge with supportive care using lung protective ventilation strategies, avoiding excess fluids, screening and treating bacterial co-infection, and timely intubation. Lower rather than upper respiratory tract viral burden correlates with clinical severity of illness.

Impact of Hyperoxia and Hypocapnia on Neurological Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage: A Retrospective Study.

In recent decades, there is increasing evidence suggesting that hyperoxia and hypocapnia are associated with poor outcomes in critically ill patients with cardiac arrest or traumatic brain injury. Yet, the impact of hyperoxia and hypocapnia on neurological outcome in patients with subarachnoid hemorrhage (SAH) has not been well studied. In the present study, we evaluated the impact of hyperoxia and hypocapnia on neurological outcomes in patients with aneurysmal SAH (aSAH). Patients with aSAH who were admitted to the intensive care unit (ICU) of a tertiary hospital in Hong Kong between January 2011 and December 2016 were retrospectively recruited. Patients' demographics, comorbidities, radiological findings, clinical grades of SAH, PO2, and PCO2 within 24 hours of ICU admission, and Glasgow Outcome Scale (GOS) at 3 months after admission were recorded. Patients with a GOS score of 3 or less were considered having poor neurological outcomes. Among the 244 patients with aSAH, 122 of them (50%) had poor neurological outcomes at 3 months. Early hyperoxia (PO2 > 200 mmHg) and hypercapnia (PCO2 > 45 mmHg) were more common among patients with poor neurological outcomes. Logistic regression analysis indicated that hyperoxia independently predicted poor neurological outcomes (OR 3.788, 95% CI 1.131-12.690, P=0.031). Classification tree analysis revealed that hypocapnia was associated with poor neurological outcomes in patients who were less critically ill (APACHE < 50) and without concomitant intracranial hemorrhage (ICH) or intraventricular hemorrhage (IVH) (adjusted P=0.006, χ 2 = 7.452). These findings suggested that hyperoxia and hypocapnia may be associated with poor neurological outcomes in patients with aSAH.

A nurse-led critical care outreach program to reduce readmission to the intensive care unit: A quasi-experimental study with a historical control group.

INTRODUCTION: Various critical care outreach services have been developed and evaluated worldwide; however, the conflicting findings indicate the need to strengthen the outreach service research. This study aimed to evaluate the effects of a nurse-led critical care follow-up program on intensive care unit (ICU) readmission and hospital mortality in patients with respiratory problems discharged from the ICU in Hong Kong. METHODS: A quasi-experimental study design, with a historical control and a prospective intervention for 13 months, was used. The intervention group received a nurse-led, multidisciplinary ICU follow-up program in addition to the usual care. The outcome measures included ICU readmission within 72 h after ICU discharge, all ICU readmission (ICU readmission irrespective of the time frame after ICU discharge), hospital mortality, and 90-day mortality rate. Logistic regression analysis was used to determine the predictors for ICU readmission within 72 h. RESULTS: A total of 369 participants (the intervention group: 185; the control group: 184) were recruited. A significant reduction in ICU readmission within 72 h was observed in the intervention group compared to the control group (p = 0.001), even after controlling for confounders (odds ratio: 0.158, p = 0.007). The intervention group also demonstrated a significant reduction in all ICU readmission (p < 0.001) and hospital mortality (p = 0.042), but not on 90-day mortality (p = 0.081), when compared with the control group. This nurse-led ICU follow-up program was shown to be cost-effective, saving an estimated US$ 145,614 for a period of 13 months. CONCLUSION: The findings demonstrated that a nurse-led multidisciplinary ICU follow-up program was a beneficial and cost-saving strategy to avert ICU readmission in patients with respiratory problems after ICU discharge. It also highlighted the competent role of ICU nurses in planning and leading the implementation of a multidisciplinary program. The results contributed to the database of an innovative follow-up program to inform the practice worldwide.

A Case of Lemierre's Syndrome in Intensive Care Unit.

We report a 21-year-old young male with Lemierre's syndrome presented as tonsillitis and Fusobacterium septicemia with respiratory failure and required intensive care. Lemierre's syndrome is the septic embolic complication of recent pharyngeal illness. Fusobacterium spp. accounts for the majority of cases. High index of suspicion is needed and prolonged antibiotic is advised. It is seldom seen in intensive care but should never be forgotten.

Impact of renal replacement therapy on survival in patients with KDIGO stage 3 acute kidney injury: A propensity score matched analysis.

AIM: To investigate the impact of renal replacement therapy (RRT) on 90-day mortality in critically ill patients suffering from KDIGO stage 3 acute kidney injury (AKI) with or without life-threatening complications using propensity score matching analysis. METHODS: We conducted a retrospective analysis of critically ill adult patients with KDIGO Stage 3 AKI with or without RRT during ICU stay between 1/1/2011-31/12/2013. Cox regression analysis and propensity score matching methods were used to determine predictors for 90-day mortality. RESULTS: Among 661 patients, 50.5% received RRT. The unadjusted 90-day mortality rate was 42.5% and 54.1% in patients who had or had not received RRT, respectively. After adjustment with propensity score based on the probability of receiving RRT, the cox regression analysis showed that RRT was associated with a lower 90-day mortality (p<0.001). Among 322 propensity-matched pairs, RRT was associated with lower ICU (23.6% vs. 39.8%, p=0.002), hospital (33.5% vs. 55.9%, p<0.001) and 90-day mortality (34.2% vs. 58.4%, p<0.001), and a higher 90-day renal recovery rate (57.8% vs. 45.3% full recovery, p=0.026) compared with no RRT. When an alternate propensity model was used, the benefits associated with RRT were very similar, except 90-day renal recovery became insignificant. CONCLUSION: Our observational study found that in critically ill patients with KDIGO Stage 3 AKI, RRT may be associated with lower 90-day mortality. The benefit of RRT on renal recovery was less prominent. Medical futility and practice variations may complicate study interpretation. To avoid these limitations, large-scale multicenter, non-observational study is recommended.

Visualization of the inferoposterior thoracic wall (VIP) and boomerang signs-novel sonographic signs of right pleural effusion.

OBJECTIVES: This study is to present the diagnostic values of the novel sonographic visualization of the inferoposterior thoracic wall (VIP) and boomerang signs in detecting right pleural effusion by sonologists with little to no experience in ultrasound. METHODS: A prospective analysis of a convenience sample of patients who were assessed by junior intensive care physicians was performed. The patients all underwent computed tomography (CT) of the chest or abdomen with lung bases as part of their care regardless of indication; the results were interpreted by radiologists and were considered the gold standard. Sonography was performed to assess for the presence of the VIP and boomerang signs. Sonographic and chest radiographic findings were compared against CT results. RESULTS: 73 patients were enrolled. The sensitivity and specificity for the VIP sign were 0.85 (95% confidence interval [CI], 0.67-0.94) and 0.86 (95% CI, 0.70-0.95). The sensitivity and specificity for the boomerang sign were 0.78 (95% CI, 0.60-0.90) and 0.87 (95% CI, 0.71-0.95). However, the sensitivity and specificity for the traditional approach of detecting an anechoic collection above the diaphragm to indicate pleural effusion were only 0.54 (95% CI, 0.37-0.71) and 0.86 (95% CI, 0.80-0.99). CONCLUSIONS: Despite inexperience in sonography, the novel VIP and boomerang signs show high diagnostic values in detecting right pleural effusion compared to the traditional methods.

Treatment of Acute Kidney Injury Complicating Septic Shock with EMiC2 High-cutoff Hemofilter: Case Series.

INTRODUCTION: Extracorporeal blood purification therapies have been proposed to improve outcomes of patients with severe sepsis, with or without accompanying acute kidney injury (AKI), by removal of excessive inflammatory mediators. MATERIALS AND METHODS: We report our experience with EMiC2 high-cutoff continuous venovenous hemofiltration/hemodialysis (HCO-CVVH/HD) in seven patients with AKI complicating septic shock. RESULTS: The median treatment duration was 71 h, and the procedure was well tolerated. Trough serum albumin level of 20 g/L was observed after 2 h of treatment and none of the patients required albumin supplement. The hospital mortality rate was 29%, which appeared more favorable than the predicted mortality of 60%-78% based on disease severity scores. Circulating levels of interleukin-6 (IL-6), IL-10, and tumor necrosis factor-alpha improved over time. CONCLUSION: This case series shows that HCO-CVVH/CVVHD using EMiC2 hemofilter may provide good cytokine modulation, when used along with good quality standard sepsis therapy. A further large-scale prospective randomized controlled trial is recommended.

Clinical Outcomes of Extended Versus Intermittent Infusion of Piperacillin/Tazobactam in Critically Ill Patients: A Prospective Clinical Trial.

STUDY OBJECTIVE: To determine whether critically ill patients receiving extended-infusion (EI) piperacillin/tazobactam would have improved clinical outcomes compared with patients receiving intermittent infusions. DESIGN: Single-center, open-label, prospective study. SETTING: Twenty-two-bed intensive care unit (ICU) in a regional hospital in Hong Kong. PATIENTS: A total of 367 adults who had a diagnosis of either bacterial infection or neutropenic fever and had received treatment with piperacillin/tazobactam for at least 48 hours between December 1, 2013, and August 31, 2015. INTERVENTION: Patients were assigned to receive piperacillin/tazobactam as either a 4-hour EI (182 patients [EI group]) or a 30-minute intermittent infusion (185 patients [non-extended infusion (NEI) group]). MEASUREMENTS AND MAIN RESULTS: All patients were followed for at least 14 days after treatment assignment. The primary outcome was the 14-day mortality rate after initiation of piperacillin/tazobactam. Secondary outcomes included in-hospital mortality rate, time to defervescence, duration of mechanical ventilatory support, length of ICU stay, and duration of hospital stay. Both groups demonstrated similar 14-day mortality (11.5% in the EI group vs 15.7% in the NEI group, p=0.29). The mean time to defervescence was significantly reduced in the EI group (4 days in the EI group vs 6 days in the NEI group, p=0.01); no significant differences between groups were noted in the other secondary outcomes. An Acute Physiology and Chronic Health Evaluation II score of 29.5 or higher was found to strongly predict 14-day mortality (p=0.03) by Classification and Regression Tree analysis. In the post hoc analyses, a 14-day mortality benefit was demonstrated in patients in the EI group in whom infectious organisms were identified (mortality rate 9.3% in the EI group vs 22.4% in the NEI group, p=0.01) and in whom respiratory tract infection was diagnosed (mortality rate 8.9% in the EI group vs 18.7% in the NEI group, p=0.02). CONCLUSION: Both the EI and NEI groups demonstrated similar 14-day mortality. Post hoc subgroup analysis revealed a mortality benefit in patients in the EI group who had infectious organisms identified or were diagnosed with respiratory tract infections.

Preoperative red cell distribution width: Not a useful prognostic indicator for 30-day mortality in patients who undergo major- or ultra-major noncardiac surgery.

BACKGROUND: Red cell distribution width (RDW) has been shown to be associated with mortality in cardiac surgical patients. This study investigates the association of RDW with the 30-day mortality for those patients who undergo major- or ultra-major noncardiac surgery. METHODS: Patients who received major- or ultra-major noncardiac surgery between July 2012 and May 2013 were included in the study and patients those with preoperative hemoglobin <10 g/day were excluded from the study. Patients were followed till day 30 from the date of surgery or death, whichever occurred earlier. RESULTS: The overall 30-day mortality for major- and ultra-major surgery was 11.4%. The mean RDW of the 30-day survivors was 13.6 ± 1.6 and that of nonsurvivors was 14.2 ± 2.1 (P < 0.001). Other factors that were significantly different (P < 0.05) between survivors and nonsurvivors included age, sex, preoperative pulse rate, current or ex-alcoholic, the American Society of Anesthesiologists score, diabetes mellitus, use of antihypertensives, sepsis with 48 h before surgery, preoperative hemoglobin, white cell count, sodium, urea, creatinine, albumin, international normalized ratio (INR), pH, base excess, estimated blood loss, and emergency surgery. Logistic regression revealed that preoperative RDW > 13.35% (P = 0.025, odds ratio [OR]: 1.52), INR (P = 0.008, OR: 4.49), albumin level (P < 0.001, OR: 1.10), use of antihypertensives (P = 0.001, OR: 1.82), and preoperative pulse rate (P = 0.006, OR: 1.02) independently predicted the 30-day mortality. However, the area under receiver operating characteristic curve for the prediction of 30-day mortality using RDW was only 0.614. CONCLUSIONS: Although preoperative RDW independently predicted 30-day mortality in patients who underwent major- or ultra-major noncardiac surgery, it may not serve as an influential prognostic indicator in view of its low sensitivity and specificity.

Septic acute kidney injury in critically ill patients - a single-center study on its incidence, clinical characteristics, and outcome predictors.

Purpose The objective of this study is to examine the incidence, clinical characteristics, and outcome (90-day mortality) of critically ill Chinese patients with septic AKI. Methods Patients admitted to the ICU of a regional hospital from 1 January 2011 to 31 December 2013 were included, excluding those on chronic renal replacement therapy. AKI was defined using KDIGO criteria. Patients were followed till 90 days from ICU admission or death, whichever occurred earlier. Demographics, diagnosis, clinical characteristics, and outcome were analyzed. Results In total, 3687 patients were included and 54.7% patients developed AKI. Sepsis was the most common cause of AKI (49.2%). Compared to those without AKI, AKI patients had higher disease severity, more physiological and biochemical disturbance, and carried significant co-morbidities. Ninety-day mortality increased with severity of AKI (16.7, 27.5, and 48.3% for KDIGO stage 1, 2, and 3 AKI, p < 0.001). Full renal recovery was achieved in 71.6% of AKI patients. Compared with non-septic AKI, septic AKI was associated with higher disease severity and required more aggressive support. Non-recovery of renal function occurred in 2.5% of patients with septic AKI, compared with 6.4% in non-septic AKI (p < 0.001). Cox regression analysis showed that age, emergency ICU admission, post-operative cases, admission diagnosis, etiology of AKI, disease severity score, mechanical ventilation, vasopressor support, and blood parameters (like albumin, potassium and pH) independently predicted 90-day mortality. Conclusions AKI, especially septic AKI is common in critically ill Chinese patients and is associated with poor patient outcome. Etiology of AKI has a significant impact on 90-day mortality and may affect renal outcome.

Recent knowledge on the pathophysiology of septic acute kidney injury: A narrative review.

Sepsis is the commonest cause of acute kidney injury in critically ill patients. Its pathophysiology is complex and not well understood. Until recently, it was believed that kidney hypoperfusion is the major contributor of septic acute kidney injury. However, recent publications have improved our understanding on this topic. We now know that its mechanisms included the following: (1) renal macrocirculatory and microcirculatory disturbance, (2) surge of inflammatory markers and oxidative stress, (3) coagulation cascade activation, and (4) bioenergetics adaptive response with controlled cell-cycle arrest aiming to prevent cell death. Uncovering these complicated mechanisms may facilitate the development of more appropriate therapeutic measures in the future.

Predictive value of plasma neutrophil gelatinase-associated lipocalin for acute kidney injury in intensive care unit patients after major non-cardiac surgery.

AIM: The performance of plasma neutrophil gelatinase-associated lipocalin (pNGAL) for prediction of acute kidney injury (AKI) in non-cardiac surgical patients has not been well described. This study investigates the use of pNGAL for early detection of AKI in patients admitted to an intensive care unit (ICU) after major or ultra-major non-cardiac surgery. METHODS: A total of 151 patients were recruited. Blood samples at 0 h and 6 h post-ICU admission were collected. Primary outcome was occurrence of AKI within 48 h of ICU admission defined using Acute Kidney Injury Network (AKIN) classification. RESULTS: Forty-five (29.8%) patients developed AKI within 48 h of ICU admission. Among them, 22, 14, and nine were classified as AKIN Stage 1, 2, and 3 respectively. pNGAL levels at 0 h and 6 h were significantly related to AKI severity. The AUROC for pNGAL at 0 h and 6 h increased with AKI severity (AKIN stage ≥1 0.671 ± 0.048 and 0.691 ± 0.047; stage ≥2 0.737 ± 0.055 and 0.796 ± 0.048; stage 3 0.829 ± 0.072 and 0.860 ± 0.065, respectively) and requirement of renal replacement therapy (0.880 ± 0.059 & 0.837 ± 0.088). Change of pNGAL from 0 h to 6 h showed no advantage in predictive power compared with pNGAL level at 0 h or 6 h alone. The addition of pNGAL into clinical AKI prediction model could only provide marginal benefit. CONCLUSION: pNGAL correlated with severity of AKI and requirement of renal replacement therapy in ICU patients who received major or ultra-major non-cardiac surgery. However, the benefit of adding pNGAL into clinical AKI prediction model is marginal.

Alteco endotoxin hemoadsorption in Gram-negative septic shock patients.

BACKGROUND AND AIMS: Severe sepsis and septic shock are common causes of mortality and morbidity in an intensive care unit setting. Endotoxin, derived from the outer membranes of Gram-negative bacteria, is considered a major factor in the pathogenesis of sepsis. This study investigated the effect of Alteco endotoxin hemoadsorption device on Gram-negative septic shock patients. MATERIALS AND METHODS: An open, controlled, prospective, randomized, single-center trial was conducted between February 2010 and June 2012. Patients with septic shock due to intra-abdominal sepsis were randomized to either conventional therapy (n = 8) or conventional therapy plus two 2-hourly sessions of Alteco endotoxin hemoadsorption (n = 7). Primary endpoint was the Sequential Organ Failure Assessment (SOFA) score changes from 0 to 72 h. Secondary end points included vasopressor requirement, PaO2/FiO2 ratio (PFR), length of stay (LOS), and 28-day mortality. RESULTS: This study was terminated early as interim analysis showed a low probability of significant findings. No significant difference was noted between the two groups with respect to change in SOFA score, vasopressor score, PFR, LOS, and 28-day mortality. Side-effect was minimal. CONCLUSIONS: We could not identify any clinical benefit on the addition of Alteco endotoxin hemoadsorption to conventional therapy in patients who suffered from intra-abdominal sepsis with shock. The side effect profile of this novel device was acceptable.

The use of regional citrate anticoagulation continuous venovenous hemofiltration in extracorporeal membrane oxygenation.

Patients on extracorporeal membrane oxygenation (ECMO) frequently requires continuous renal replacement therapy (CRRT). Additional anticoagulation for the CRRT circuit is usually not employed, but this may increases the risk of clot embolization, which shortens oxygenator lifespan and increases patient's risk. We report our experience on the use of regional citrate anticoagulation continuous venovenous hemofiltration (RCA-CVVH) connected to an ECMO circuit, which could be useful during low heparin or heparin-free ECMO situations. Regional citrate anticoagulation continuous venovenous hemofiltration was performed using AK200US machine with a blood flow of 150 ml/min, Acid Citrate Dextrose Solution prefilter infusion at 240 ml/hr, ultrafiltration rate of 2,040 ml/hr, and postdilutional online generated replacement fluid infused as appropriate. The circuit was aimed to run for 30 hrs. From May 2009 to May 2013, 63 patients received ECMO and 29 received RCA-CVVH. The median total CVVH time was 131 hrs (interquartile range [IQR]: 61-224 hrs), and hemofilter life was 27.2 hrs (IQR: 25.7-28.5 hrs). No hemofilter or oxygenator was changed because of clotting. Their hospital mortality was 27.6%. There were eight patients, who were judged to be too sick for anticoagulation, received predilution CRRT during the same period. Their hospital mortality was 75%. In conclusion, online postdilutional RCA-CVVH connected to an ECMO circuit is a feasible, safe, and effective CRRT technique.

Timing for initiation of continuous renal replacement therapy in patients with septic shock and acute kidney injury.

The optimal timing for renal replacement therapy initiation in septic acute kidney injury (AKI) remains controversial. This study investigates the impact of early versus late initiation of continuous renal replacement therapy (CRRT) on organ dysfunction among patients with septic shock and AKI. Patients were dichotomized into "early" (simplified RIFLE Risk) or "late" (simplified RIFLE Injury or Failure) CRRT initiation. Patients with chronic kidney disease stage 5 or those on long-term dialysis were excluded. Organ dysfunction was quantified by Sequential Organ Failure Assessment (SOFA) score. From January 2008 to June 2011, 120 patients fulfilled the inclusion criteria. Thirty-one (26%) underwent "early" while 89 (74%) had "late" CRRT. No significant difference was noted between groups on improvement of total SOFA/non-renal SOFA score or noradrenaline equivalent in the first 24 and 48 h after CRRT initiation. Dialysis requirement and mortality (at 28 days, 3 months and 6 months) did not differ. In conclusion, improvement of non-renal SOFA score 48 h after CRRT correlated with SOFA score on CRRT initiation (P = 0.040) and APACHE IV risk of death (P = 0.000), but not estimated glomerular filtration rate on CRRT initiation (P = 0.377). Improvement of non-renal SOFA score correlated with SOFA score on CRRT initiation and APACHE IV risk of death. However, this retrospective review cannot identify any significant clinical benefit of early CRRT initiation in patients presenting with septic shock and AKI.

Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection.

BACKGROUND: Experience from influenza pandemics suggested that convalescent plasma treatment given within 4 to 5 days of symptom onset might be beneficial. However, robust treatment data are lacking. METHODS: This is a multicenter, prospective, double-blind, randomized controlled trial. Convalescent plasma from patients who recovered from the 2009 pandemic influenza A(H1N1) (A[H1N1]) infection was fractionated to hyperimmune IV immunoglobulin (H-IVIG) by CSL Biotherapies (now BioCSL). Patients with severe A(H1N1) infection on standard antiviral treatment requiring intensive care and ventilatory support were randomized to receive H-IVIG or normal IV immunoglobulin manufactured before 2009 as control. Clinical outcome and adverse effects were compared. RESULTS: Between 2010 and 2011, 35 patients were randomized to receive H-IVIG (17 patients) or IV immunoglobulin (18 patients). One defaulted patient was excluded from analysis. No adverse events related to treatment were reported. Baseline demographics and viral load before treatment were similar between the two groups. Serial respiratory viral load demonstrated that H-IVIG treatment was associated with significantly lower day 5 and 7 posttreatment viral load when compared with the control (P = .04 and P = .02, respectively). The initial serum cytokine level was significantly higher in the H-IVIG group but fell to a similar level 3 days after treatment. Subgroup multivariate analysis of the 22 patients who received treatment within 5 days of symptom onset demonstrated that H-IVIG treatment was the only factor that independently reduced mortality (OR, 0.14; 95% CI, 0.02-0.92; P = .04). CONCLUSIONS: Treatment of severe A(H1N1) infection with H-IVIG within 5 days of symptom onset was associated with a lower viral load and reduced mortality. TRIAL REGISTRY: ClinialTrials.gov; No.: NCT01617317; URL: www.clinicaltrials.gov.