Hypertonic Saline Dextran Ameliorates Organ Damage in Beagle Hemorrhagic Shock.

OBJECTIVE: The goal of this study was to investigate the effect of hypertonic saline with 6% Dextran-70 (HSD) resuscitation on organ damage and the resuscitation efficiency of the combination of HSD and lactated ringers (LR) in a model of hemorrhage shock in dogs. METHODS: Beagles were bled to hold their mean arterial pressure (MAP) at 50 ± 5 mmHg for 1 h. After hemorrhage, beagles were divided into three groups (n = 7) to receive pre-hospital resuscitation for 1 h (R1): HSD (4 ml/kg), LR (40 ml/kg), and HSD+LR (a combination of 4 ml/kg HSD and 40 ml/kg LR). Next, LR was transfused into all groups as in-hospital resuscitation (R2). After two hours of observation (R3), autologous blood was transfused. Hemodynamic responses and systemic oxygenation were measured at predetermined phases. Three days after resuscitation, the animals were sacrificed and tissues including kidney, lung, liver and intestinal were obtained for pathological analysis. RESULTS: Although the initial resuscitation with HSD was shown to be faster than LR with regard to an ascending MAP, the HSD group showed a similar hemodynamic performance compared to the LR group throughout the experiment. Compared with the LR group, the systemic oxygenation performance in the HSD group was similar but showed a lower venous-to-arterial CO2 gradient (Pv-aCO2) at R3 (p < 0.05). Additionally, the histology score of the kidneys, lungs and liver were significantly lower in the HSD group than in the LR group (p < 0.05). The HSD+LR group showed a superior hemodynamic response but higher extravascular lung water (EVLW) and lower arterial oxygen tension (PaO2) than the other groups (p < 0.05). The HSD+LR group showed a marginally improved systemic oxygenation performance and lower histology score than other groups. CONCLUSIONS: Resuscitation after hemorrhagic shock with a bolus of HSD showed a similar hemodynamic response compared with LR at ten times the volume of HSD, but HSD showed superior efficacy in organ protection. Our findings suggest that resuscitation with the combination of HSD and LR in the pre-hospital setting is an effective treatment.

[Detoxification effects of two drugs in thallium -poisoned mice].

OBJECTIVE: To observe the thallium eliminating effect of prussian blue, pentetate zinc trisodium (Zn-DTPA), and their combined use in the treatment of acute thallium poisoning in mice. METHODS: Thallium poisoned mice were reproduced by oral administration of 0.2 ml thallous nitrate (3 mg/ml). They were assigned randomly to four groups according to the random number table method, namely, model group, prussian blue group, Zn-DTPA group and the combination therapy group, with 10 mice in each group. Prussian blue was administered orally [4.52 g×kg(-1)×d(-1), total four times], and Zn-DTPA was injected intraperitoneally [500 mg×kg(-1)×d(-1), one time]4 hours after giving thallium. The dosage of both drugs in combination treatment was as the same as described above. After treatment for 5 days, all the animals were sacrificed. Brain, intestine, kidney and liver of 1 mouse from each group were collected for pathological examination to observe the necrosis. Thallium contents of blood, brain, urine and feces from the other mice were determined. RESULTS: Pathological examination showed that the damage to intestine, kidney and liver was less obvious in treatment group compared with those of the model group. The effect was most obvious in the combination treatment group. However, brain damage was slightly improved. Thallium content in blood (mg/ml) of prussian blue group and the combination treatment group decreased obviously compared with the model group, and the decrease was more obvious in the combination treatment group (0.05 ± 0.01 vs. 0.18 ± 0.02). Thallium content in urine (mg/ml) and feces (mg/kg) was significantly increased after treatment, and the thallium elimination was most significant in the combined treatment group (urine: 11.34 ± 0.81 vs. 0.02 ± 0.01, feces: 13.11 ± 1.84 vs. 0.21 ± 0.07, both P < 0.01). Thallium content in brain was similar among all the groups. CONCLUSIONS: The single and combined use of prussian blue and Zn-DTPA could reduce the damage in intestine, kidney and liver. Combined use of prussian blue and Zn-DTPA for acute thallium poisoning mice is more efficacious than single use of either drug.

[Studying the therapeutic effects of hemoperfusion with continuous venovenous hemofiltration on the patients with acute paraquat poisoning].

OBJECTIVE: To explore the therapeutic effects of hemoperfusion (HP) with continuous venovenous hemofiltration (CVVH) on the patients with acute paraquat poisoning. METHODS: Ninety-one patients with acute paraquat poisoning were randomly divided into HP group (49 cases) and HP-CVVH group (42 cases). The mortality, survival duration and the death causes between the two groups were compared and analyzed. RESULTS: There were no significant differences in mortality (59.2% versus 61.9%) between the two groups. The mean time between poisoning and death in HP-CVVH group was (4.9 +/- 3.1) days, which was significantly longer than that (3.5 +/- 2.0) days in HP group (P < 0.05). The death proportion on 4th day after poisoning in HP group was 62.1% (18/29), which was significantly higher than that (30.8%, 8/26) in HP-CVVH group (P < 0.05). The hypoxia appeared in 4.3 +/- 2.5 days after poisoning in HP-CVVH group, which was significantly longer than that (3.2 +/- 1.9) days in HP group (P < 0.05). The mortality due to respiratory failure in HP group was 20.4% (10/49), which was significantly lower than that (40.5%, 17/42) in HP-CVVH group (P < 0.05). The incidence of acute renal failure in HP group was 63.3% (31/49), which was significantly higher than that (40.5%, 17/42) in HP-CVVH group (P < 0.05). CONCLUSION: The combined therapy of HP and CVVH can prevent the patients with acute paraquat poisoning from early death and prolong the survival duration, but can not reduce mortality for the patients with acute paraquat poisoning.

[Study on the prognosis of patients with acute paraquat intoxication].

OBJECTIVE: To study the correlation factors of acute paraquat intoxication prognosis. METHODS: The early paraquat concentration in plasma and urine, leukocyte count, hepatic and renal function, amylase, electrolyte and the parameters of arterial blood gas were analyzed retrospectively in 111 patients with acute paraquat intoxication. RESULTS: 43 cases (38.7%) of all the 111 patients survived and the other 68 cases (61.3%) died. The patient, whose paraquat concentration was not more than 8.0 µg/ml in plasma and 276.0 µg/ml in urine, could survive. But some patients could die, only if there was no paraquat found in plasma. The paraquat levels in plasma and urine were significantly lower in survivors [(0.82 ± 1.70), (28.12 ± 51.17) µg/ml] than in nonsurvivors [(9.32 ± 12.04), (384.53 ± 597.93) µg/ml, respectively] (P < 0.01). The levels of leukocyte count, serum creatinine, aspartate aminotransferase (AST), and amylase were significantly higher in nonsurvivors than in survivors (P < 0.05, P < 0.01). In addition, metabolic acidosis was easier to appear in nonsurvivors. The multiple logistic regression analysis indicated that the paraquat concentration in plasma and urine, leukocyte count, creatinine and base excess were all related to survival. CONCLUSION: The higher paraquat concentration in plasma and urine, leucocytosis, renal dysfunction and metabolic acidosis are all important factors for the prognosis of paraquat intoxication.

Pharmacokinetics and safety of a new bioengineered thrombolytic agent, human tissue urokinase type plasminogen activator in Chinese healthy volunteers.

The aim of our study was to investigate the pharmacokinetics and safety of human tissue urokinase type plasminogen activator (HTUPA) in healthy Chinese subjects after intravenous administration. Thirty-two subjects were given intravenous injection doses of 5-35 mg of HTUPA for safety evaluation. Twenty-four subjects were given 10, 20 or 30 mg HTUPA for pharmacokinetic assessment. Safety and tolerance were evaluated by monitoring adverse events, laboratory parameters, electrocardiography and vital signs. HTUPA concentration in human serum samples was determined by an enzyme-linked immunosorbent assay (ELISA) method. The main pharmacokinetic parameters were calculated by DAS software. HTUPA was generally well tolerated and in the whole study course no serious adverse events occurred. The main pharmacokinetic parameters were as follows: geometric mean [95% confidence interval, CI] for t1/2 were 1.5 (1.4, 1.6), 1.3 (1.2, 1.4), and 1.2 (1.2, 1.3) h, AUC0-t were 1.0 (0.7, 1.3), 2.1 (1.5, 2.7), and 5.6 (4.7, 6.6) mg h L(-1), AUC0-∞ were 1.1 (0.8, 1.3), 2.1 (1.5, 2.7), and 5.8 (4.7, 6.7) mg h L(-1) for 10, 20, and 30 mg group, respectively. The main pharmacokinetic parameters were not significantly different between males and females (P>0.05). No serious adverse events were reported by the subjects or revealed by clinical or laboratory examinations, suggesting the given doses were safe and well tolerated.

[The diagnostic value of butyrylcholinesterase in acute organophosphorus pesticide poisoning].

OBJECTIVE: To assess the value of butyrylcholinesterase (BuChE) in the diagnosis of acute organophosphorus pesticide poisoning (AOPP), and to investigate the relationship between the activity of whole blood acetylcholinesterase (AChE) and plasma BuChE in patients of AOPP in order to re-evaluate the diagnostic value of BuChE. METHODS: An improved Ellman method was employed to determine the activity of AChE and BuChE in 21 AOPP inpatients due to different kinds of pesticides (from April to September in 2009) during the course of the illness, with 26 healthy volunteers as normal control. The relationship between BuChE activity and other clinical indicators of 113 inpatients (from January 2008 to April 2009) was also retrospectively analyzed. RESULTS: The normal value of AChE and BuChE were (105 + or - 33) U/Hb and (15 807 + or - 3 495) U/L . The inhibition levels of these two enzymes were different. When the AChE activity was lower than 50%, 30% or 20%, the activity of BuChE was lower than 20%, 10% or 5% correspondingly. The tendency of changes in the two enzymes was similar and coincided well with the clinical symptoms after poisoning. The results of sequential detection showed that a significant decrease or persistent inhibition of BuChE activity by less than 5% indicated a high level of organophosphorus pesticide in the body. However, an elevation of BuChE indicated a favorable outcome. CONCLUSION: BuChE is one of the ideal diagnostic and classification criteria for AOPP. When the inhibition level of BuChE reaches 20%, AOPP is of moderate degree, when it reaches 10%, severe AOPP can be diagnosed, with different kinds of organophosphorus pesticides taken into consideration.