The epidemiology of acute respiratory distress syndrome in pediatric intensive care units in China.

OBJECTIVE: To assess the incidence of, predisposing factors for, and the rates and relative risks of mortality from acute respiratory distress syndrome (ARDS) in pediatric patients. DESIGN: A prospective study in 12 consecutive months from 2004 to 2005 in 25 pediatric intensive care units (PICUs). PATIENTS AND SETTING: ARDS was diagnosed according to the 1994 American-European Consensus Conference definitions, applied to all severely ill admissions between 1 month and 14 years of age. The PICUs were in major municipalities and provincial cities, and half were university affiliated. MEASUREMENTS AND RESULTS: From a total of 12,018 admissions, 7,269 were severely ill. One hundred and five (1.44%) patients developed ARDS and 64 (61.0%) died, which accounts for 13.2%, of the total ICU death (n = 485, 6.7%) or a nine times relative risk of dying. The median age at onset of ARDS was 24 months and 40% were less than 12 month old. Median time from PICU admission to the onset of ARDS was 16 h, and in 63% <24 h. Pneumonia (55.2%) and sepsis (22.9%) were the major predisposing factors for ARDS. These were respectively 14 and 5 times as high a death rate as those of the severely ill patients without ARDS. CONCLUSIONS: ARDS has a high mortality in these Chinese PICUs, especially in those with pneumonia and sepsis, and adequate management including lung protective ventilation strategy is required.

[Prospective, multicenter study of mortality and risk factors in children with acute respiratory distress syndrome in 25 pediatric intensive care units in China].

OBJECTIVE: To investigate the mortality and predictors of outcome of children with acute respiratory distress syndrome (ARDS) in pediatric intensive care unit (PICU). METHODS: ARDS cases were selected from the 12 018 patients admitted in 25 pediatric intensive care units in China from January 1 to December 31, 2004, aged 29 days to 14 years, using the Chinese Pediatric Critical Index of Severity (PCIS) and American Guidelines for Admission and Discharge Policies for PICU. ARDS was diagnosed according to the 1994 American-European Consensus Conference criteria. RESULTS: 105 of the 12 018 patients (1.44%) were diagnosed as with ARDS. The overall mortality of ARDS was 61.0% (64/105), 9 times as high as that of the 7269 severe cases in PICU. Logistic regression analysis showed that infiltration shadows in 2 - 3 quadrants, pediatric critical illness score (PCIS), and partial pressure of carbon dioxide (PaCO2) at the onset of ARDS were independently associated with the mortality. CONCLUSION: ARDS has a high risk of death, and the infiltration shadows in 2-3 quadrants, PCIS, and PaCO2 are independently associated with mortality.

[Effects of hydrocortisone on circulating and intramyocardial inflammatory mediators in severe septic rats with myocardial injury induced by Escherichia coli].

OBJECTIVE: Severe sepsis and septic shock remain the most common cause of death in intensive care units. The main causes of death in sepsis are the cardiac dysfunction and hypotension resistant to cateolamines. The prevalence of relative adrenal insufficiency in severe sepsis and septic shock was estimated at about 32%-51%. Several meta-analysis demonstrated that high-dose glucocorticoids decreased survival during sepsis, while stress doses of corticosteroids may benefit these patients. The exact reason for such widely divergent outcome produced by different doses of corticosteroid is still not understood. Therefore, the study was undertaken to observe the effects of different doses of hydrocortisone (HC) on circulating and intramyocardial inflammatory mediators in severe septic rats with myocardial injury induced by Escherichia coli (E. coli). METHODS: The model was established by two injections of inactivated E. coli Forty male Wistar rats were randomly divided into five groups: high-dose of HC group (150 mg/kg), medium-dose group (20 mg/kg), low-dose group (6 mg/kg), model group (NS substituted for HC), and control group (NS for E. coli and HC). Each group had eight rats. After 2 hours of treatment, specimens were collected to measure serum cardiac troponin I (cTnI), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), nitric oxide (NO) and total NO synthase (NOS). NO and total NOS in myocardial homogenate were also detected. The expression of inducible NOS (iNOS) of myocytes was investigated. RESULTS: All the above-mentioned markers in model group significantly higher than those in control group. After HC injection, serum cTnI concentrations in low-dose group decreased to normal values compared to that of model group, while in another two HC groups, the concentrations were higher than those in model group. TNF-alpha level was not significantly influenced. But IL-1beta level declined to normal values, being prominent in low-dose HC group. Neither high-dose nor middle-dose HC could lower serum NO or total NOS, but low-dose HC could greatly inhibit both NO and NOS levels (P < 0.05). There was no significant difference in the level of NO and total NOS of myocardial homogenate between left and right ventricles. There was no iNOS expression by normal myocardium, while the expression in model group was significantly increased. After HC injection, the iNOS expressions by myocardium in three HC groups were weaker than those in model group. The intensity of iNOS signals became weak with the decrease in HC dose. CONCLUSION: Different doses of HC might exert different effects on circulating and intramyocardial inflammatory mediators in severely septic rats with myocardial injury induced by E. coli. Low-dose HC could significantly inhibit such mediators as well as iNOS expression by cardiomyocytes. The results suggest that low dose HC exert protective effect on myocardial injury of severely septic rats.

[Effects of different doses of hydrocortisone on acute lung injury in rats with early septic shock induced by Escherichia coli].

OBJECTIVE: To observe the effects of different doses of hydrocortisone (HC) on acute lung injury (ALI) and inflammatory response in rats at early stage of septic shock induced by Escherichia coli and to investigate the possible mechanisms for such differences. METHODS: ALI model of early septic shock was induced in rats by two injections of Escherichia coli at 5 hours interval, with the first intraperitoneal injection of 6.50 x 10(10) cfu/kg and followed by an external jugular vein injection of 2.00 x 10(11) cfu/kg. Forty Wistar rats were randomly divided into the following five groups: normal control, ALI without HC treatment, high-dose HC (150 mg/kg), medium-dose HC (20 mg/kg) and low-dose HC (6 mg/kg). Two hours after the treatment, the specimens were collected for histopathological examination and the biological indexes of lung injury were measured. The expressions of intercellular adhesion molecule-1 (ICAM-1) and glucocorticoid receptor (GR) in lung tissues were also investigated by immunohistochemical assays. RESULTS: The biological indexes of lung injury [wet/dry weight ratio (g/g), total protein concentration in bronchoalveolar lavage fluid (mg/L) and lung permeability index (10(-3))] in ALI group (4.76 +/- 0.10, 278.96 +/- 60.45, 4.73 +/- 0.60) were significantly increased as compared to those in normal control group (4.10 +/- 0.07, 67.46 +/- 13.27, 1.12 +/- 0.15) (P < 0.05). The grades of ALI pathologic changes in ALI group (11.13 +/- 1.13) was significantly higher than that in the normal control group (0.50 +/- 0.53, P < 0.05). The ratio of expression area of ICAM-1 in ALI group (0.149 +/- 0.037) was significantly increased as compared to that in the normal control group (0.051 +/- 0.018) (P < 0.05). The ratio of expression area of GR all group (0.043 +/- 0.037) was significantly decreased as compared to that in the normal Control group (0.124 +/- 9.040) (P < 0.05) After administration of HC, all the lung injury indexes, pathological grades and the ratios of expression area of ICAM-1 and GR were significantly improved, with the most remarkable effects observed in the low-dose HC group. The expressions of ICAM-1 and GR showed a significantly negative linear correlation (r = 0.55, P < 0.0001). CONCLUSION: These results indicated that the low-dose HC treatment had the most remarkable effects of improving the biological indexes of lung injury, inflammatory mediators and pathological changes. These HC dose dependent therapeutic effects might be associated with the level of GR expression.

[Effects of aminoguanidine in different dosages on renal function in endotoxin induced rabbits shock model].

OBJECTIVES: To explore the effects of aminoguanidine (AG) in different dosages on renal function in endotoxin induced rabbits shock model in the early stage and to approve the effects of dose-depended and time-depended of AG. METHODS: Fourty New Zealand rabbits under anaesthesia were randomly divided into 5 groups: sham group, LPS group, the first group of AG, the second group of AG, the third group of AG. Each rabbits from the four groups received Escherichia Coli O55B5 LPS 400 micro g/kg to induce endotoxic shock except sham group. Edotoxic shock was diagnosed when the mean arterial pressure (MAP) decreased to 30%. Each rabbits in sham group and LPS group received 5ml NS, in the other three groups were infused with AG 30 mg/kg (the first group of AG), 50 mg/kg (the second group of AG), 100 mg/kg (the third group of AG) in 5ml NS, respectively. Urine output was recorded at the following time points, before injecting IPS (T(0)), shock (T), 1 h (T(1)), 2 h (T(2)), 3 h (T(3)), 4 h (T(4)), 5 h (T(5)) and 6 h (T(6)) after shock. Plasma nitrate and nitrite (NO(3)(-)/NO(2)(-), stable products of NO), BUN, Scr, RBP were determined at the time points of T, T(2), T(4) and T(6). RESULTS: LPS increased NO(3)(-)/NO(2)(-), BUN, Scr, RBP [from (47 +/- 5) micro mol/L, (5.8 +/- 1.5) mmol/L, (41 +/- 10) micro mol/L, (240 +/- 61) ng/L (T(0)) to (160 +/- 18) micro mol/L, (15.5 +/- 1.8) mmol/L, (166 +/- 23) micro mol/L, (1580 +/- 180) ng/L (T(6)), respectively, P < 0.01]; Urine output decreased significantly [from (17.6 +/- 2.8) ml (T(0)) to (1.3 +/- 0.6) ml (T(6)), P < 0.01]. AG attenuates the increasing of NO(3)(-)/NO(2)(-), BUN, Scr and RBP, and decreasing of urine output. NO(3)(-)/NO(2)(-) of the first, second and third group of AG at T(6) were (58 +/- 8), (50 +/- 14) and (46 +/- 9) micro mol/L, respectively. Compared to LPS group, there was a significant difference (P < 0.01). BUN was (8.2 +/- 2.9), (7.5 +/- 1.9) and (5.5 +/- 1.8) mmol/L, respectively at T(6). Compared to LPS group, there was a significant deference (P < 0.01). RBP was (350 +/- 60), (272 +/- 72) and (248 +/- 103) ng/L, respectively at T(6) (compared to LPS group, there was a significant deference. P < 0.05, < 0.05, < 0.01). Urine output was (11. 1 +/- 2.4), (12. 1 +/- 1. 3) and (17.1 +/- 2. 4) ml, respectively on T(6) (compared to LPS group, there was a significant deference, P < 0.01). AG of 100 mg/kg showed the best effect among three AG groups. CONCLUSION: AG inhibited NO formation in dose-depended and time depended way. AG attenuated the changes of renal function induced by NO.

[Transcranial Doppler monitoring of cerebral blood flow velocity during extracorporeal membrane oxygenation in sheep].

OBJECTIVE: To investigate the hemodynamics during extracorporeal membrane oxygenation (ECMO) and the value of transcranial Doppler (TCD) monitoring. METHODS: ECMO was conducted on 14 sheep. TCD monitoring was conducted at different time-points to examine the bilateral cerebral blood flow velocity (CBFV), including systolic peak flow velocity (Vs), end-diastolic flow velocity (Vd), mean flow velocity (Vm), and pulse index (PI, Vs-Vd/Vm). The general condition, blood pressure, heart rate, and temperature were observed. Two weeks after, the surviving 9 sheep were killed, their brains were taken out and morphological and pathological examinations were done. RESULTS: Anesthesia showed little effect on CBFV. After the ligation of carotid artery and vein, the CBFV pattern only changed slightly, Vs and PI decreased, and Vm and Vd remained almost unchanged. During ECMO with either greater or smaller volume, especially the former, the CBFV pattern showed a non-pulse waves, Vs markedly decreased with a value hardly different from that of Vd, Vs, Vd, and Vm were 62%, 75%, and 69% of the values in normal condition. The pre-ECMO CBFV was not significantly different from those examined any day after ECMO. The differences of pH and PO(2) in femoral artery during different stages were insignificant. PaCO(2) during ECMO with great flow volume and during mechanical ventilation after ECMO was significantly lower than that before ECMO (P < 0.05). The MABP of femoral artery during ECMO with small flow volume was significantly lower than that before ECMO (P < 0.05). Vm was positively correlated with MABP and not correlated with heart rate and temperature. The gross observation of the sheep's brain was normal. Small foci of malacia were seen in the brains of 4 sheep. CONCLUSION: Hemodynamics changes remarkably during ECMO. TCD monitors the CBFV continuously during ECMO, thus helping maintaining the stability of CBFV and protect the brain.

[Effect of dexamethasone, aminoguanidin, amrinone on oxygen utilization in endotoxin shock rabbits].

OBJECTIVE: To investigate the effect of three kinds of drug with different mechanism, dexamethasone (Dex), aminoguanidin (AG) and amrinone (Amr) on oxygen utilization in endotoxic shock rabbits. METHODS: Thirty-five rabbits were randomly allocated into five groups: operation, lipopolysaccharide (LPS), Dex, Amr and AG. The endotoxin shock was induced by intravenously injecting LPS (400 micro g/kg). The arterial blood gas, mixed venous blood gas and cardiac output were recorded at 30 min after the operation (T(0)), shock status (T), 1 - 6 h after the treatment (T(1)-T(6)). The oxygen delivery (DO(2)), oxygen consumption (VO(2)) and extraction ratio of oxygen (ERO(2)) were calculated. RESULTS: All the parameters in five groups showed no significant differences (P > 0.05) at T(0). Six hours after treatment, rabbits in Dex group presented with significantly improved DO(2) (12.4 +/- 3.1) ml/(kg.min), P < 0.01 and VO(2) (5.1 +/- 1.6) ml/(kg.min), P < 0.05 compared with DO(2) (8.1 +/- 2.4) ml/(kg.min) and VO(2) (2.7 +/- 1.0) ml/(kg.min) in LPS group. Rabbits in AG group showed significantly increased DO(2) (17.0 +/- 2.8) ml/(kg.min) (P < 0.01), (17.2 +/- 2.5) ml/(kg.min) (P < 0.05), compared with (12.2 +/- 2.6), (14.1 +/- 3.8) ml/(kg.min) in LPS group at T(1) and T(2), respectively, but there was no significant difference (11.2 +/- 1.7) ml/(kg.min) (P > 0.05) at T(6). The VO(2) increased significantly, (5.0 +/- 1.0) ml/(kg.min) (P < 0.01) compared with LPS group at T(6). The VO(2) of Amr group was significantly higher than LPS group at T(3) and T(4). At T(6), the DO(2) and VO(2) were (9.5 +/- 1.3) and (4.1 +/- 1.5) ml/(kg.min), respectively, but there was no significant difference compared with LPS group. There was no significant difference in ERO(2) among groups (P > 0.05). CONCLUSION: The dexamethasone, aminoguanidin, amrinone can improve oxygen utilization in endotoxic shock rabbits, especially for dexamethasone and aminoguanidin.

[Clinical application of simplified pediatric critical illness scoring system].

OBJECTIVE: To simplify the Pediatric Critical Illness Scoring (PCIS), to evaluate the simplified PCIS and to make the simplified scoring system applicable in the grassroots hospitals. METHODS: Totally 1,036 patients were scored by PCIS on 1, 3, 7 and the last (discharged or dead) hospital days. The PCIS has 10 items. The full score is 100. The scores of approximately 100, approximately 80, and approximately 70 represent non-serious, serious, and extremely serious patients' condition. The PaO(2) and pH (2 items), BUN or creatinine (3 items), plasma sodium and potassium (5 items) were deleted from PCIS's 10 items in turn. The remaining 8, 7, and 5 items were applied as new scoring system after the original scores were multiplied by 0.8, 0.7, and 0.5. The simplified PCIS was evaluated by comparing the patients' condition that was assessed by PCIS. The consistency rate of patients' condition that was obtained by using PCIS and simplified PCIS should be over 80%. The mortality of non-serious, serious, and extremely serious groups that were defined by using PCIS and simplified PCIS was observed and compared. RESULTS: When 2, 3 and 5 items were deleted from the PCIS on d1 scoring the consistency rates of the patients' condition were 82.6%, 80.7%, and 69.9%. While 5 items remained on d1 scoring the consistency rate was lower than 80%. When the same 2, 3 and 5 items were deleted from PCIS on d3, d7 and last scoring, the consistency rates of the patients' condition were 81.5% approximately 97.1%. The PCIS and simplified PCIS had a close correlation (r = 0.629-0.948, P < 0.001). In PCIS the mortality rates of non-serious, serious and extremely serious patients were significantly different. When simplified PCIS was used, the mortality rates of the three groups also had significant differences (chi(2) = 86.13-740.33, P < 0.001). Within a group of patients with the same condition, the mortality rates were not significantly different for PCIS and simplified PCIS. For instance, on d1 and last scoring, the mortality rates of extremely serious patients were 29.8%, 67.3% for PCIS and 30.0%-27.9%, 66.3%-64.4% for simplified PCIS. CONCLUSION: When 2 items (PaO(2) and pH) were deleted from d1 PCIS scoring and 5 items (PaO(2) and pH, BUN or creatinine, plasma sodium and potassium) were deleted from d3, d7, and last PCIS scoring, the results of assessment of patients' condition were basically the same as those of PCIS. The consistency rates of PCIS and simplified PCIS were > 80%. When simplified PCIS was applied, mortality rates of non-serious, serious, and extremely serious patients were significantly different that were the same as those of PCIS. In patients with the same condition, the mortality rates were not significantly different between the simplified PCIS and PCIS.

On-line lung volume measurement during high-frequency oscillatory ventilation.

OBJECTIVE: A bag-in-box system using a closed-circuit helium-dilution technique was used to determine the functional residual capacity during conventional mechanical ventilation. The purpose of this study was to determine whether the bag-in-box system could be used to measure mean lung volume without interrupting high-frequency oscillatory ventilation. DESIGN: Laboratory study. SETTING: Hospital intensive care medical research laboratory. SUBJECTS: Six mechanical lung models and ten New Zealand adult rabbits. INTERVENTIONS: The bag-in-box system was introduced into the respiratory circuit during the study. The rabbits were randomly divided into a healthy group and an acute lung injury group. Acute lung injury was induced by intravenously infusing oleic acid during conventional mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: In a lung model study, a series of rebreathing processes were performed. By measuring the helium concentration in each process, the rebreathing time needed for equilibration was found to be about 50 secs. We compared the measured volume with a known lung volume to test the method's accuracy. The volumes differed by -0.5% to 4.4%. Measured and known volumes of different size lung models correlated well (p <.001). Equilibration of helium in the system occurred after 40-50 secs of rebreathing in healthy rabbits and 30-40 secs of rebreathing in rabbits with acute lung injury. Of 45 mean lung volume determinations in ten rabbits, the coefficient of variation ranged from 0.5% to 6.5%. When mean airway pressure changed, the mean lung volume alteration was detected by the method, but it was inconsistent in each mean airway pressure variation. CONCLUSION: A bag-in-box apparatus using a helium-dilution technique could be evaluated as a method to measure gas-containing lung volumes ranging from 10 to 60 mL in patients receiving high-frequency oscillatory ventilation.