Continuous hemodiafiltration as a rescue therapy for patients with cardiopulmonary failure caused by enterovirus-71: a retrospective observational study in a PICU.

BACKGROUND: Hand, foot and mouth disease (HFMD) remains a burdensome health issue in mainland China. Enterovirus71 (EV-A71) is the main pathogen of severe HFMD. Continuous hemofiltration improves fluid overload, restores kidney function and alleviates inflammatory reactions. The aim of the present study was to evaluate the effects of continuous veno-venous hemodiafiltration (CVVHDF) on severe HFMD caused by EV-A71(EV-A71-HFMD) in a pediatric intensive care unit (PICU). METHODS: A retrospective observational study was performed in a tertiary university PICU from January 2012 to December 2016. Children with severe EV-A71-HFMD complicated by cardiopulmonary failure were included. The patients were divided into a CVVHDF group and a conventional therapy (control) group (non-CVVHDF). The demographics, characteristics, and outcomes between the groups were collected and analyzed. RESULTS: Twenty-nine patients with severe EV-A71-HFMD were enrolled. The 28-day mortality was 17.6% (3/17) in the CVVHDF group and 33.3% (4/12) in the non-CVVHDF group, with no statistical significance between the two groups (P = 0.403). The median interval between CVVHDF initiation and PICU admission was 6 (4,8.5) hrs, and the median duration of CVVHDF was 48 (36, 64) hrs. The left ventricular ejection fraction (LVEF) and cardiac index (CI) in the CVVHDF group were improved after treatment. The plasma levels of catecholamines and renin-angiotensin-aldosterone system (RAAS) substances in the CVVHDF group were significantly decreased after treatment. The decreased catecholamines and RAAS substances included adrenalin (169.8 [145.5, 244.6] vs. 148.0 [109.0, 208.1] ng/L, P = 0.033), dopamine (152.7 [97.0, 191.1] vs. 96.0 [68.0, 160.9] ng/L, P = 0.026), angiotensin II (185.9 [125.2, 800.0] vs. 106.0 [90.8, 232.5] ng/L, P = 0.047), aldosterone (165.7 [94.0, 353.3] vs. 103.3 [84.3, 144.3] ng/L, P = 0.033), and renin (1.12 [0.74, 3.45] vs. 0.79 [0.52, 1.25] µg/L/h, P = 0.029), CONCLUSIONS: CVVHDF reduced the levels of catecholamines and RAAS substances and improved cardiovascular function. Continuous hemodiafiltration may represent a potential therapy in patients with severe EV-A71-HFMD complicated with cardiopulmonary failure.

A Survey of the First-Hour Basic Care Tasks of Severe Sepsis and Septic Shock in Pediatric Patients and an Evaluation of Medical Simulation on Improving the Compliance of the Tasks.

BACKGROUND: Application of the sepsis resuscitation bundle is limited by clinician knowledge, skills, and experience. We used the adjusted first-hour basic care tasks in pediatric patients in three tertiary hospitals in Shanghai, China. OBJECTIVE: The aim of this study is to survey the compliance of the adjusted tasks and to evaluate in situ simulation team training on improving the compliance. METHODS: A prospective observational study was performed with the survey checklists from May 2011 to January 2012 in three pediatric intensive care units. A simulated case scenario was administered to the practitioners in one hospital. RESULTS: Seventy-three patients were enrolled, including 47 patients in one simulation hospital (SH) and 26 patients in two nonsimulation hospitals (NSH). The total compliance of the tasks was 47.9% (35/73). The compliance in the SH was significantly higher compared to that in the NSHs (61.7% [29/47] vs. 23.1% [6/26], p < 0.01). Compared to the SH, the main problems in the NSH were giving intravenous or intraosseous fluid resuscitation in a longer time (35.3 min vs. 19.9 min, p = 0.000), a smaller percentage of measurement of accurate urine output (38.5% vs. 68.1%, p = 0.027), delivering high-flow oxygen (73.1% vs. 93.6%, p = 0.028), and measurement of lactate (69.2% vs. 100%, p = 0.000). CONCLUSIONS: In situ simulation team training is an effective method of teaching the tasks of septic shock care to clinicians and nurses on the front line and of improving the compliance of the tasks.

[A comparison of high versus standard-volume hemofiltration in critically ill children with severe sepsis].

OBJECTIVE: High-volume hemofiltration (HVHF) is an potential therapy for the treatment of sverve sepsis in intensive care unit, but little information is avialible in children. The aim of our study was to evaluate the effects of HVHF compared with standard-volume continuous veno-venous hemofiltration (CVVH) for critically ill children with severe sepsis, and to evaluate the feasibility and tolerance. METHODS: A single-center prospective trial was performed on the data of critically ill children with sverve sepsis, who were treated with 48hours HVHF (effluent rate 50 - 70 ml . kg-1 . h-1) versus more than 48hours CVVH(effluent rate 35 ml . kg-1 . h-1) from May, 2009 to April, 2014 in Shanghai Children's Hospital, Shanghai Jiao Tong University. Biomarkers and clinical outcomes were compared between the HVHF and standard-volume CVVH groups included 28-day mortality, lengths of PICU stays, vasopressor dose reduction and adverse events. RESULTS: A total of 72 critically ill patients with severe sepsis comfirmed less than 72 hours were enrolled. male 42 cases (58. 3%) and female 30 cases (41. 7%) , median age was 56 months(range from 3 to 168 months). Patients were randomized to either HVHF(n =34) at 50 - 70 ml . kg-1 . h-1 or standard-volume CVVH (n = 38). There were no significant difference either PRISM III score or pediatric critical illness score between HVHF and standard-volume CVVH group (P > 0. 05). Death occurred in 24 cases, the total mortality was 33. 3%. Mortality at 28 days was lower than expected but not statistically significant differences HVHF 29.4% comnared with standard-volume CVVH 36.8% (χ2 = 0. 45, P = 0. 50). After blood hemofiltration therapy the dosage of heparin in HVHF group are lower than CVVH group (P <0. 05) . Complications of hypernatremia, alkali imbalance and glucose abnormalities in HVHF group is higher than that of standard-volume CVVH group (P <0. 05 or P <0. 01). CONCLUSIONS: Compared with standard -volume CVVH, HVHF is safe on severe sepsis in children and is trend to reduce the case fatality rate. But still expect the multi-center and larger sample study for evaluation the 28 days mortality in pediatric critically ill with severe sepsis.

Inhibition of microRNA­155 relieves sepsis­induced liver injury through inactivating the JAK/STAT pathway.

The present study aimed to investigate whether the microRNA (miR)­155 inhibitor has an anti­inflammatory effect on sepsis­associated liver injury and whether this effect is associated with the activity of the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. BALB/c mice were randomly divided into three groups (n=40 per group): Control, lipopolysaccharide (LPS) and miR­155 inhibitor plus LPS groups. Liver injury was induced by injection of LPS (20 mg kg­1). In the inhibitor plus LPS group, LPS was administered after injecting the miR­155 inhibitor (80 mg kg­1) for 3 days. Liver tissues were collected at 6, 12, 24 and 48 h after LPS exposure. Hematoxylin and eosin was used to identify the histological changes in the liver. The expression levels of miR­155, suppressor of cytokine signaling 1 (SOCS1) and STAT1 were determined by reverse transcription­quantitative polymerase chain reaction. The protein expression of tumor necrosis factor (TNF)­α and interleukin (IL)­10 were detected by ELISA. miR­155 inhibitor pretreatment alleviated the symptoms of LPS­exposed mice, and reduced LPS­induced mortality and liver injury. Compared with the LPS group, expression of miR­155 was significantly reduced in the miR­155 inhibitor plus LPS group at 6 h (P<0.05). SOCS1 expression was significantly increased in miR­155 inhibitor plus LPS group compared with the control and the LPS group at 12 h (P<0.05). There was a lower level of STAT1 in the miR­155 inhibitor plus LPS group compared with the LPS group (P<0.05). In addition, TNF­α and IL­10 were significantly decreased in the miR­155 inhibitor plus LPS group compared with the LPS group (P<0.05). In conclusion, the miR­155 inhibitor relieves liver injury by enhancing the expression of SOCS1 and inactivating JAK/STAT signaling.

[Central venous-to-arterial carbon dioxide difference in critically ill pediatric patients with septic shock].

OBJECTIVE: To assess the value of central venous-to-arterial carbon dioxide difference [ P( cv-a) CO2] in evaluation of disease severity and prognosis in children with septic shock who already had central venous oxygen saturation (ScvO2) higher than 70% after early resuscitation. METHOD: In this prospective study, 48 septic shock children seen in Shanghai Children's Hospital, Shanghai Jiao Tong University were enrolled from Jun 2012 to May 2014. 36(75.0%) were male, 12 (25.0%) were female, the average age was (31.9 ± 24.5) months. The critically ill patients with septic shock were treated to achieve ScvO2greater than 70% depending on early goal-directed therapy (EGDT). All patients were divided into two groups, based on P(cv-a)CO2, low P(cv-a)CO2group with P(cv-a)CO2< 6 mmHg (1 mmHg = 0.133 kPa) and high P(cv-a)CO2group with P(cv-a)CO2≥ 6 mmHg. The parameters of hemodynamics including mean blood pressure (MAP), heart rate (HR), central venous pressure (CVP), perfusion-related parameters [ScvO2, P(cv-a)CO2, serum lactate (Lac), Lac clearance rate], pediatric critical illness score, PRISMIII score, and 28 days in-hospital mortality were recorded for all patients. RESULT: Of the 48 cases with septic shock whose ScvO2was higher than 70%, 17 patients (35.4%) had high P(cv-a)CO2( ≥ 6 mmHg) and 31 (65.6%) had lower P(cv-a)CO2(<6 mmHg). There were no significant differences between the 2 groups of patients in age, PRISMIII score and PCIS (P > 0.05 ), but Lac and P(cv-a)CO2values were significantly different ( P < 0.05). Low P(cv-a) CO2group patients had lower 28 days mortality than high P(cv-a) CO2group[11/17 vs. 32.3% (10/31), P < 0.05]; 24 h after resuscitation, compared with high P(cv-a) CO2group, low P(cv-a) CO2group patients had lower Lac values [(2.0 ± 1.3) vs.( 2.7 ± 1.2) mmol/L, P < 0.05]. Low P(cv-a) CO2group patients had shorter duration of vasoactive drugs use [(16 ± 14) vs. (44 ± 21)h, P < 0.05], 24 h Lac clearance rate was significantly higher for low P(cv-a) CO2group than for high P(cv-a) CO2group[ (31 ± 10) % vs. (26 ± 6)%, P < 0.05]. CONCLUSION: When ScvO2> 70% was achieved after early resuscitation in septic shock children, P(cv-a) CO2is a sensitive biomarker to assess tissue perfusion, and high P(cv-a) CO2group patients had poor outcome.

[Changes and significance of soluble CD 163 in sepsis and severe sepsis in children].

OBJECTIVE: To investigate the changes of serum soluble CD 163 (sCD 163) level, to assess the severity of critical illness and to evaluate the immune status of sepsis or severe sepsis in children. METHOD: A prospective study was conducted. The sCD 163 was determined in 50 cases with sepsis or severe sepsis in pediatric intensive care unit (PICU) and 23 cases of age- and gender-matched healthy children were enrolled as control during the period from April 2010 to March 2011. Double-antibody sandwich ELISA was used for sCD 163 measurement. The relationship with sCD 163 level and disease severity score (pediatric critical illness score, PCIS; and pediatric risk of mortality III, PRISM III), lymphocyte subsets, C-reactive protein (CRP), tumor necrosis factor α (TNFα) were analyzed. RESULT: The sCD 163 in sepsis/severe sepsis groups (171.04 ± 177.85) mg/L was significantly higher than that in control group (44.19 ± 86.48) mg/L (P < 0.01).sCD 163 in sepsis group [(105.32 ± 145.87) mg/L] was significantly lower than that of severe sepsis group [(233.32 ± 171.78) mg/L] (P < 0.05). sCD 163 level was significantly higher in lower PCIS score patients. (P < 0.01). The sCD 163 levels was higher in PRISM III ≥ 10 than the PRISM III < 10 group. The sCD 163 levels were higher in death group than the survival group. The sCD 163 was negatively correlated with CD4 +, CD4 +/CD8 + (R = -0.820, P < 0.05; R = -0.839, P < 0.01). CONCLUSION: Detection of sCD 163 was helpful in predicting the severity of sepsis and severe sepsis, and sCD 163 may reflect the immune status of critically ill children with sepsis.

[Efficacy of continuous blood purification on rescue therapy of the critically ill children with acute lung injury and acute respiratory distress syndrome].

OBJECTIVE: To investigate the efficacy of continuous blood purification(CBP) in the treatment of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in children. METHODS: One hundred and forty seven cases of ALI/ARDS were hospitalized to our pediatric intensive care unit, and 32 cases were treated with continuous blood purification (CBP) from June, 2006 to May, 2011. The model for CBP was continuous veno-venous hemofiltration dialysis (CVVHDF). CBP treatment persisted for at least 8 hours and replacement + dialysis fluid dose was 35 - 100 ml/(kg·h). The clinical outcome measures included the mortality rate at 28th day, respiratory index (FiO2/PO2), dynamic lung compliance (Cdyn), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), mechanical ventilation parameters, vasoactive drug dose and lung X-ray changes. RESULTS: In totally 147 cases of ALI/ARDS, 89 cases (60.5%) were male and 58 (39.5%) were female, mean age was (43.4 ± 36.7) months. Death occurred in 54 cases, the total mortality was 36.7%. The cause of ALI/ARDS was mainly severe pneumonia, severe sepsis, and leukemia or tumor diseases. There were significant differences in severity of illness between the CBP treatment group and non-CBP treatment group on Pediatric risk of score mortality (PRISM) III score (15.3 vs. 12.7, P < 0.05) and pediatric critical illness score (66.8 ± 19.3 vs. 74.6 ± 17.7, P < 0.05). The average duration of CBP treatment was 52 hours (12 hours to 232 hours). PaO2/FiO2 and Cdyn were improved after 2 hours CBP treatment compared with those before CBP treatment (P < 0.05), mechanical ventilation parameters including fraction of inspired oxygen (FiO2), peak inspiratory pressure (PiP) and positive end expiratory pressure (PEEP) were reduced. The use of vasoactive drugs in patients with MODS and shock gradually declined. The average ventilator-free days of the two groups did not show significant difference (P > 0.05). The mortality on CBP treatment group and non-treatment group were 37.5% and 36.5%, respectively, the difference was not significant (P > 0.05). CONCLUSION: CBP adjuvant treatment for ALI/ ARDS could reduce pulmonary edema, improve PaO2/FiO2 and Cdyn, and improve mechanical ventilation parameters. CBP may be a very promising treatment for ALI/ARDS in children.

Glucocorticoid receptor expression on acute lung injury induced by endotoxin in rats.

BACKGROUND: In cases of severe sepsis and septic shock, a series of pathophysiological changes lead to multiple organ dysfunction syndrome. This study aimed to investigate the expression of glucocorticoid receptor mRNA in the rat lung following endotoxin (LPS) induced shock. METHODS: Totally 56 SD rats were randomly divided into 4 groups: LPS shock group (n=16), LPS+vasoactive intestinal peptide group(VIP) group, (n=16), LPS+VIP+ glucocorticoid (GC) group, (n=16),and control group (n=8). LPS shock was induced by intravenous injection of LPS (10 mg/kg) in rats. Within 15 minutes after LPS injection, rats in the treatment groups received VIP (5 nmol/kg) or VIP and methylprednisolone (3 mg/kg). The control group was given normal saline instead of LPS. The rats of the four groups were sacrificed at 6 hours,24 hours after injection respectively, and the lung tissues were collected. Pathological changes of the lungs were examined by light microscopy and electron microscopy. GRmRNA expression in the lung tissues was evaluated by RT-PCR. RESULTS: In the LPS shock group, lung histopathology demonstrated destruction of the alveolar space,widening of the inter-alveolar space, inflammatory cell infiltration and interstitial edema. However,pathological changes in the LPS+ VIP group and LPS+ VIP+GC group were milder than those in the LPS shock group. Six hours after LPS injection, GR mRNA expression was down-regulated in the LPS group (0.72± 0.24) and LPS+ VIP group (0.88±0.27) (P<0.05) as compared with the control group (1.17±0.22). The LPS shock group showed a more significant down-regualtion than the LPS+VIP group, but the difference was not statistically significant (P>0.05). In contrast, GRmRNA expression in the LPS+ VIP+GC group was significantly up-regulated at 6 hours and further at 24 hours (1.45±0.32 and 1.91±0.46 respectively) (P<0.05). CONCLUSION: GrmRNA expression decreased in LPS induced lung injury in rats. Combined treatment with VIP and GC mitigated lung injury ang inflammation. The mechanism may be related to up-regulation of GR mRNA expression.