Wing-Wa Yan

Delayed Clearance of Viral Load and Marked Cytokine Activation in Severe Cases of Pandemic H1N1 2009 Influenza Virus Infection

Abstract Background. Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological profile of different clinical severity are lacking. Methods. We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-without-ARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. Results. Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. Conclusions. The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death.

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.

Over 8 years experience on severe acute poisoning requiring intensive care in Hong Kong, China

In order to obtain up-to-date information on the pattern of severe acute poisoning and the characteristics and outcomes of these patients, 265 consecutive patients admitted to an intensive care unit in Hong Kong for acute poisoning from January 2000 to May 2008 were studied retrospectively. Benzodiazepine (25.3%), alcohol (23%), tricyclic antidepressant (17.4%), and carbon monoxide (15.1%) were the four commonest poisons encountered. Impaired consciousness was common and intubation was required in 67.9% of admissions, with a median duration of mechanical ventilation of less than 1 day. The overall mortality was 3.0%. Among the 257 survivors, the median lengths of stay in the intensive care unit and acute hospital (excluding days spent in psychiatric ward and convalescent hospital) were less than 1 day and 3 days, respectively. Factors associated with a longer length of stay included age of 65 or older, presence of comorbidity, Acute Physiology and Chronic Health Evaluation II score of 25 or greater, and development of shock, rhabdomyolysis, and aspiration pneumonia, while alcohol intoxication was associated with a shorter stay. This is the largest study of its kind in the Chinese population and provided information on the pattern of severe acute poisoning requiring intensive care admission and the outcomes of the patients concerned.

Regional citrate anticoagulation in predilution continuous venovenous hemofiltration using prismocitrate 10/2 solution.

Regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) is associated with a longer filter life and fewer bleeding events. Complexity of the regimen is the major hurdle preventing widespread application. This study describes a simple predilution continuous venovenous hemofiltration (CVVH) protocol utilizing a commercially prepared replacement solution containing citrate (Prismocitrate 10/2). Ten patients with acute renal failure were evaluated. The Prismaflex system was used for predilution CVVH, with Prismocitrate 10/2 running at 2500 mL/h as the main predilution replacement. An 8.4% sodium bicarbonate solution was infused at 50 mL/h in the first 2 h followed by 30 mL/h; 10% calcium gluconate was given to achieve an ionized calcium (iCa) level of 1–1.2 mmol/L. The circuit was run for 72 h unless there was filter clotting, transportation was required, or the patient did not require further CRRT. Total treatment duration was 504.5 h. The post‐dilution equivalent ultrafiltration rate was 32.9 mL/kg/h (interquartile range [IQR] 31.6–38.2) and the median circuit life was 50.3 h (IQR 25.5–72.0). None of the circuit was changed due to circuit clotting. The median systemic iCa was 0.98 mmol/L (IQR 0.91–1.08). The total calcium‐to‐iCa ratio was 2.33 (IQR 2.21–2.45). None of the patients developed hypernatremia (Na ≥ 150 mmol/L) or citrate toxicity (total Ca‐to‐iCa ratio > 2.5 plus increasing metabolic acidosis), and metabolic alkalosis (pH ≥ 7.5) occurred in one patient. This simple RCA CVVH protocol using commercially‐prepared solution could be a feasible, relatively safe, and effective alternative to the conventional regimen for patients with a body weight up to 80 kg.

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.

A Retrospective Review of the Use of Regional Citrate Anticoagulation in Continuous Venovenous Hemofiltration for Critically Ill Patients

Background. The emergence of a commercially prepared citrate solution has revolutionized the use of RCA in the intensive care unit (ICU). The aim of this study was to evaluate the safety profile of a commercially prepared citrate solution. Method. Predilution continuous venovenous hemofiltration (CVVH) was performed using Prismocitrate 10/2 at 2500 mL/h and a blood flow rate of 150 mL/min. Calcium chloride solution was infused to maintain ionized calcium within 1.0–1.2 mmol/L. An 8.4% sodium bicarbonate solution was infused separately. Treatment was stopped when the predefined clinical target was reached or the filter clotted. Result. 58 sessions of citrate RCA were analyzed. The median circuit lifetime was 26.0 h (interquartile range IQR 21.2–44.3). The percentage of circuits lasting more than 12 h, 24 h, and 48 h was 94.6%, 58.9%, and 16.1%, respectively. There was no incidence of hypernatremia and median pH was <7.5. Hypomagnesemia and hypophosphatemia were detected in 41.6% and 17.6% of blood samples taken, respectively. Although 16 episodes had a total calcium/ionized calcium (total Ca/iCa) >2.5, only four patients had evidence of citrate accumulation. Conclusion. The commercially prepared citrate solution could be used safely in critically ill patients who required CVVH with no major adverse events.

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

Abstract 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.

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

To determine whether critically ill patients receiving extended‐infusion (EI) piperacillin/tazobactam would have improved clinical outcomes compared with patients receiving intermittent infusions.

Prevention of ventilator-associated pneumonia.

Ventilator-associated pneumonia is the commonest, yet mostly preventable, infection in mechanically ventilated patients. Successful control of ventilator-associated pneumonia can save hospitalisation cost, and is possible by using a multidisciplinary clinical and administrative approach. The ventilator-associated pneumonia rate should be expressed as the number of ventilator-associated pneumonia days per 1000 ventilator days to take into account the device-utilisation duration for meaningful comparison. Various strategies address the issue, including general infection control measures, body positioning, intubation and mechanical ventilation, oral and gastro-intestinal tract, endotracheal tube, airway pressure, cuff pressure, selective digestive and/or oropharyngeal decontamination, and probiotic or early antibiotic treatment, as well as overall administration at a policy level. The rationale and controversy of these approaches are discussed in this article. The authors suggest that all units treating mechanically ventilated patients should have a ventilator-associated pneumonia prevention protocol in place, and ventilator-associated pneumonia should be seriously considered as a key performance indicator in local intensive care units.

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.