Influence of continuous veno-venous hemofiltration on the course of acute pancreatitis

AIM: To investigate whether continuous veno-venous hemofiltration (CVVH) in different filtration rate to eliminate cytokines would result in different efficiency in acute pancreatitis, whether the saturation time of filter membrane was related to different filtration rate, and whether the onset time of CVVH could influence the survival of acute pancreatitis. METHODS: Thirty-seven patients were classified into four groups randomly. Group 1 underwent low-volume CVVH within 48 h of the onset of abdominal pain (early CVVH, n = 9). Group 2 received low-volume CVVH after 96 h of the onset of abdominal pain (late CVVH, n = 10). Group 3 underwent high-volume CVVH within 48 h of the onset of abdominal pain (early CVVH, n = 9). Group 4 received high-volume CVVH after 96 h of the onset of abdominal pain (late CVVH, n = 9). CWH was sustained for at least 72 h. Blood was taken before hemofiltration, and ultrafiltrate was collected at the start of CVVH and every 12 h during CVVH period for the purpose of measuring the concentrations of TNPα, IL-1β and IL-6. The concentrations of TNPα, IL-1β and IL-6 were measured by swine-specific ELISA. The Solartron 1 255 B frequency response analyzer (British) was used to observe the resistance of filter membrane. RESULTS: The survival rate had a significant difference (94.44% vs 68.42%, P<0.01) high-volume and low-volume CVVH patients. The survival rate had also a significant difference (88.89% vs 73.68%,P<0.05) between early and late CVVH patients. The hemodynamic deterioration (MAP, HR, CVP) was less severe in groups 4 and 1 than that in group 2, and in group 3 than in group 4. The adsorptive saturation time of filters membranes was 120-180 min if the filtration rate was 1 000-4 000 mL/h. After the first, second and third new hemofilters were changed, serum TNF-α concentrations had a negative correlation with resistance (r: -0.91, -0.89, and -0.86, respectively in group 1; -0.89, -0.85, and -0.76, respectively in group 2; -0.88, -0.92, and -0.82, respectively in group 3; -0.84, -0.87, and -0.79, respectively in group 4). The decreasing extent of TNF-α, IL-1β and IL-6 was significantly different between group 3 and group 1 (TNF-α P<0.05, IL-1β P<0.05, IL-6 P<0.01), between group 4 and group 2 (TNF-α P<0.05, IL-1β P<0.05, IL-6 P<0.01), between group 1 and group 2 (TNP-α P<0.05, IL-1β P<0.05, IL-6 P<0.05), and between group 3 and group 4 (TNF-α P<0.01, IL-1β P<0.01, IL-6 P<0.05), respectively during CVVH period. The decreasing extent of TNF-α and IL-1β was also significantly different between survival patients and dead patients (TNF-α P<0.05, IL-1β P<0.05). In survival patients, serum concentration of TNF-α and IL-1β decreased more significantly than that in dead patients. CONCLUSION: High-volume and early CVVH improve hemodynamic deterioration and survival in acute pancreatitis patients. High-volume CVVH can eliminate cytokines more efficiently than low-volume CVVH. The survival rate is related to the decrease extent of TNF-α and IL-1β. The adsorptive saturation time of filter membranes are different under different filtration rate condition. The filter should be changed timely once filter membrane adsorption is saturated.     

The effect of intensive plasma water exchange by hemofiltration on hemodynamics and soluble mediators in canine endotoxemia

High volume hemofiltration (HVHF) (200 ml/kg/h) improves hemodynamics in experimental septic shock but is difficult to apply clinically. Accordingly, we studied whether less intensive HVHF (80 ml/kg/h) can still improve hemodynamics in experimental septic shock. We also investigated its effect on the serum concentrations of several inflammatory mediators, including endothelin (ET-1), endotoxin (LPS), tumor necrosis factor-alpha (TNF-alpha), and 6-keto prostaglandin F(1alpha) (6-kepto PGF(1alpha)). Sixteen anesthetized dogs were connected to a continuous veno-venous hemofiltration (CVVH) (filtration: 80 ml/kg/h) or sham circuit and endotoxin (0.5 mg/kg) was infused intravenously over 5 min. Hemodynamic variables were measured at baseline and at 15, 45, 90, and 180 min. The major hemodynamic finding was that endotoxin-induced hypotension was significantly attenuated by intensive CVVH (p < 0.04). Changes in cardiac output and right ventricular ejection fraction were equal in both groups. ET-1 levels, but not LPS, TNF-alpha, or 6-keto PGF(1alpha), were lower during CVVH (p = 0.042). Endotoxin or TNF-alpha were not found in the ultrafiltrate. Median clearances of ET-1 and 6-keto PGF(1alpha) during intensive CVVH were 8.8 and 25.9 ml/m, respectively. We conclude that intensive CVVH attenuates the early component of endotoxin-induced hypotension and reduces serum concentrations of endothelin-1. The effect of CVVH on blood pressure is not explained by convective clearance of the mediators in question.     

Effects of octreotide on central hemodynamics and systemic oxygen use in patients with viral cirrhosis

OBJECTIVE: Octreotide has potentially beneficial effects in patients with cirrhosis. However, the effects of octreotide on central hemodynamics and oxygen use have not been established. The present study was undertaken to evaluate the effect of octreotide on central hemodynamics and oxygen use in patients with viral cirrhosis. METHODS: Twenty-five patients with cirrhosis were enrolled in the study. They were randomly assigned to receive either placebo (n = 10) or a continuous infusion of 100 microg/h of octreotide after an initial 100-microg bolus (n = 15). Hemodynamic measurements and oxygenation values were obtained before and 60 min after octreotide or placebo administration. RESULTS: Placebo administration did not have any effect on hemodynamic and oxygenation values. In patients who received octreotide, systemic hemodynamic values including cardiac index, mean arterial pressure, and systemic vascular resistance were not affected. The mean pulmonary arterial pressure tended to increase after octreotide administration but was statistically insignificant. There was a significant increase in pulmonary arterial vascular resistance, whereas the pulmonary capillary wedge pressure and right atrial pressure were significantly decreased. Arterial oxygen tension, systemic oxygen uptake, and oxygen extraction ratio were significantly decreased after octreotide administration, whereas oxygen transport as well as arterial and mixed venous oxygen contents remained unchanged. CONCLUSIONS: In patients with viral cirrhosis, octreotide administration exerted a significant effect on pulmonary circulation. It also resulted in a decrease in systemic oxygen uptake and oxygen extraction ratio. These results suggested that octreotide may impair tissue oxygenation in patients with viral cirrhosis.     

急性肺血栓栓塞症猪血流动力学及心肌损伤的研究

目的　观察急性肺血栓栓塞症 (PTE)猪血流动力学、动静脉血气及心肌肌钙蛋白Ⅰ(cTnⅠ )、肌红蛋白 (Mb)、肌酸激酶同工酶 (CK MB)水平。方法　健康幼年猪 16只 ,分为 2组 ,每组8只。栓塞组 (急性PTE模型组 ) :用注射器经颈外静脉插管快速 1次注入多聚乙烯微球 ,0 1g/kg体重悬浮于生理盐水 5 0ml中 ;对照组 :用注射器经颈外静脉插管快速 1次注入生理盐水 5 0ml。检测栓塞前、栓塞后即刻、30min、1h、2h、3h血流动力学及血气的变化 ,同时检测血清cTnⅠ、Mb、CK MB水平。结果　栓塞即刻肺动脉压升高 ,约为栓塞前的 2～ 3倍 ,栓塞后 2～ 3h逐渐恢复至栓塞前水平 ;心输出量、肺毛细血管嵌顿压、肺动脉压收缩压、舒张压无明显变化。栓塞即刻动脉血氧分压(PaO2 )下降 ,动脉血二氧化碳分压升高 ,pH值下降 ,30～ 6 0min达最高峰 ,2h后PaO2 和 pH值恢复至栓塞前水平。栓塞后血清cTnⅠ和Mb明显升高 ,CK Mb栓塞前后无明显变化。cTnⅠ与Mb有相关性 (r =0 5 5 ,P =0 0 0 1) ,与CK MB无相关性 (r =0 10 9,P =0 5 33)。结论　急性PTE可出现急性肺动脉压升高和气体交换障碍等病理生理改变。检测cTnⅠ和Mb有助于急性PTE心肌损伤早期诊断     

连续静脉-静脉血液滤过对多脏器功能障碍综合征血流动力学的影响

目的 :探讨连续静脉 静脉血液滤过对多脏器功能障碍综合征 (MODS)患者血流动力学的影响。方法 :选择MODS患者 19例 ,应用连续静脉 静脉血液滤过 (CVVH)进行治疗 ,治疗期间用Swan Ganz漂浮导管监测血流动力学变化。结果 :与CVVH前比较 ,CVVH治疗后 ,体血管阻力指数明显改善 ,平均动脉压回升 ,心率下降 ,肺动脉楔压也明显降低。结论 :CVVH可改善MODS患者的全身血流动力学状况 ,提高患者的氧供 ,但对氧摄取率无明显影响     

Mechanical ventilation affects local and systemic cytokines in an animal model of acute respiratory distress syndrome.

We examined the hypothesis that injurious ventilatory strategies (large tidal volume [VT] and/or low positive end-expiratory pressure [PEEP]) would increase release of inflammatory mediators into the lung and into the systemic circulation in a lung injury model. Lung injury was induced in 40 anesthetized paralyzed Sprague-Dawley rats (350 +/- 2 g) by hydrochloric acid instillation (pH 1.5, 2.5 ml/kg). Rats were then randomized into five groups (n = 8): (1) high-volume zero PEEP (HVZP): VT, 16 ml/ kg; (2) high-volume PEEP (HVP): VT, 16 ml/kg, PEEP, 5 cm H2O; (3) low-volume zero PEEP (LVZP): VT, 9 ml/kg; (4) low-volume PEEP (LVP): VT, 9 ml/kg, PEEP, 5 cm H2O; (5) same settings as (4) plus a recruitment maneuver performed every hour (LVPR). Respiratory rate was adjusted to maintain normocapnia and fraction of inspired oxygen (FIO2) was 1. Cytokine concentrations (tumor necrosis factor-alpha [TNF-alpha] and macrophage inflammatory protein-2 [MIP-2]) were measured by ELISA. All animals in the LVZP group died before the end of the experiment. After 4 h of ventilation, the HVZP group had similar lung fluid TNF-alpha concentrations compared with the HVP group: 1,861 +/- 333 pg/ml versus 1,259 +/- 189 pg/ml; and much higher serum concentrations: 692 +/- 74 pg/ml versus 102 +/- 31 pg/ml (p < 0.05). An identical pattern was found for MIP-2. These results suggest that the particular ventilatory strategy can affect the release of cytokines into the systemic circulation, a finding that may have relevance for the development of multisystem organ failure.     

Dobutamine in severe scorpion envenomation: effects on standard hemodynamics, right ventricular performance, and tissue oxygenation.

OBJECTIVES: To document the effects of dobutamine on standard hemodynamics and right ventricular (RV) performance in patients exhibiting pulmonary edema following severe scorpion envenomation, and to characterize the tissue oxygenation profile in patients sustaining scorpion envenomation-related shock. DESIGN: Prospective cohort study. SETTING: An ICU in a university hospital. PATIENTS: Nineteen consecutive patients were admitted to the ICU for severe scorpion envenomation; all 19 patients exhibited hemodynamic pulmonary edema, and 10 patients had peripheral shock. INTERVENTIONS: All patients underwent a hemodynamic study with a Swan-Ganz catheter. In 8 of 19 patients, the thermodilution catheter was equipped with a fast-response thermistor. MEASUREMENTS AND RESULTS: Standard hemodynamic parameters were recorded on admission and following the infusion of dobutamine in all patients at a dosage, from 7 to 20 microg/kg/min, intended to achieve the best hemodynamic and tissue oxygenation compromise. RV ejection fraction (RVEF) and RV volumes were simultaneously recorded in 8 patients, and tissue oxygenation parameters were assessed in the 10 patients with peripheral shock. The clinical signs of tissue hypoperfusion improved, and optimal hemodynamic parameters were achieved at a mean +/- SD dobutamine dosage of 17 +/- 7 microg/kg/min. Dobutamine infusion evoked statistically significant increases in cardiac index, from 2.3 +/- 0.6 to 3.6 +/- 0.7 L/min/m2; stroke volume index, from 18 +/- 5 to 31 +/- 10 mL/m2; and systemic arterial pressure, from 64 +/- 12 to 78 +/- 14 mm Hg. Pulmonary artery occlusion pressure (PAOP) and venous admixture decreased significantly: from 23 +/- 4 to 15 +/- 6 mm Hg and from 29 +/- 7% to 20 +/- 5%, respectively. With respect to RV function, dobutamine infusion significantly increased the RVEF, from 24 +/- 7% to 42 +/- 9%, without significantly changing the RV end-diastolic volume index, reflecting an enhanced RV contractility. In patients with peripheral circulatory failure, the baseline tissue oxygenation profile was consistent with cardiogenic shock, showing increased oxygen extraction as a consequence of a striking depression in oxygen delivery (DO2). After dobutamine infusion, DO2 improved significantly, from 386 +/- 104 to 676 +/- 156 mL/min/m2, with a significant decrease in oxygen extraction, from 34 +/- 8% to 24 +/- 6%. CONCLUSIONS: In severe scorpion envenomation, dobutamine infusion improves impaired heart function. The effects involve both left ventricular and RV dysfunction. Impaired tissue oxygenation is also improved.     

Amrinone during porcine intraperitoneal sepsis

Seven Yucatan minipigs with chronic, severe intraperitoneal sepsis were given amrinone i.v. (loading dose of 0.75 mg/kg, followed by continuous infusion of 10, 20, 40, and 80 micrograms/kg/min) during the hyperdynamic phase of sepsis. Hemodynamic variables and oxygen utilization, delivery, and extraction were recorded throughout the study. Pulmonary capillary wedge pressure was kept constant to ensure a fixed ventricular filling pressure. Intravenous amrinone modestly augmented cardiac index without altering heart rate. Mean systemic and pulmonary arterial pressures decreased. Systemic and pulmonary vascular resistance fell significantly (P less than 0.05). Amrinone did not significantly alter oxygen utilization or oxygen extraction, although oxygen delivery increased (P less than .05). During the hyperdynamic phase of sepsis in this animal model, amrinone elicits vasodilatation with a modest improvement in stroke volume index. Consequently, cardiac output and oxygen delivery increased modestly. Because of its vasodilating properties and small salutary effects, amrinone is not an optimal first-line medication for hemodynamic stabilization during hyperdynamic sepsis.     

Prediction of Pulmonary Arterial Pressure Level after Repair of Congenital Cardiac Communications and Discharge from the Hospital: Role of Down Syndrome and Early Postoperative Hemodynamics

Background: Postoperative pulmonary hypertension limits the success of surgical treatment in some patients with unrestrictive congenital cardiac communications. Identifying patients at risk of developing postoperative pulmonary hypertension is important to individualize follow-up strategies. Methods: We analyzed a prospective cohort of 52 pediatric patients (age 3 to 35 months) looking for perioperative predictors of mildly elevated pulmonary arterial pressure 6 months after surgery, defined as a systolic pressure greater than 30 mmHg by transthoracic echocardiography. This corresponds to a mean pulmonary arterial pressure of >20 mmHg. Clinical, echocardiographic and hemodynamic parameters were investigated. Perioperative hemodynamics was assessed by directly measuring pulmonary and systemic arterial pressures using indwelling catheters. Early postoperative pulmonary hemodynamics was defined as the mean pulmonary/systemic mean arterial pressure ratio (PAP/SAP) obtained per patient during the first 6 h of postoperative care. Results: Among the factors that were investigated as possible predictors, perioperative hemodynamics and the presence of Down syndrome were initially selected using univariate analysis (p < 0.030). Early postoperative PAP/SAP was correlated with PAP/SAP obtained in the operating room just after cardiopulmonary bypass (r = 0.70, p < 0.001), and it was higher in subjects with Down syndrome than in nonsyndromic individuals (p = 0.003). Early postoperative PAP/SAP was the only predictor selected using multivariate analysis. It was characterized as an independent predictor after adjustments for possible confounders. An early postoperative PAP/SAP of >0.35 was 76% sensitive and 74% specific at predicting a systolic pulmonary arterial pressure of >30 mmHg 6 months after surgery (hazard ratio with 95% CI 8.972 [2.428–33.158], p = 0.002). Conclusion: The hypertensive early postoperative behavior of the pulmonary circulation was strongly but not exclusively associated with Down syndrome, and it was characterized as an independent predictor of altered pulmonary arterial pressure after discharge from the hospital.     

Effects of verapamil on pulmonary arterial pressure in patients with cor pulmonale complicated by heart failure

In this study, observation of the effects of verapamil on pulmonary arterial pressure and on treating right heart failure were done in 15 patients with chronic cor pulmonale complicated with heart failure using monitoring of hemodynamic changes by right cardiac catheter. The results showed that verapamil had remarkable effect on pulmonary arterial pressure. With no significant effect on systemic blood pressure, verapamil decreases right ventricular systolic pressure by 1.3 kPa (9.6 mmHg), pulmonary arterial systolic pressure by 1.5 kPa (11 mmHg) and mean pulmonary arterial pressure by 1.1 kPa (8.5 mmHg). Verapamil is clinically useful by decreasing cardiac afterload, improving cardiac function, treating right heart failure and relieving bronchial spasm.     

Inhaled nitric oxide improves oxygenation in piglets with meconium aspiration

We hypothesized that nitric oxide (NO) inhalation in a model of meconium aspiration in newborn piglets would decrease pulmonary vascular resistance. Seven neonatal piglets were obtained at less than 48 hr of age and instrumented under fentanyl anesthesia. Inhaled NO (40 parts per million) was administered during normoxia and again after hypoxia was induced by reducing FiO, to 0.13. During normoxia NO inhalation caused a fall in pulmonary artery pressure from a mean of 3.15 (SD 0.8) kPa to 2.84 (SD 0.7) kPa (P < 0.01). Hypoxia (mean arterial 0, saturation 35%) increased PA pressures to a mean of 5.4 (SD 1.6) kPa and NO administration during hypoxia decreased PA pressures to 3.6 (SD 1.2) kPa (P < 0.001). In order to determine the effects of NO in a model of meconium aspiration, 6 to 7 mUkg of 20% human meconium in normal saline was instilled into the trachea. This procedure induced hypoxemia (mean SaO, 43.4%, SD 19), respiratory acidosis, (mean PaCO, 12.1 kPa, SD 0.5; mean pH 7.04, SD 0.03), and pulmonary arterial hypertension (mean pulmonary artery pressure 6.0 kPa, SD 1.3) despite ventilation with 90% oxygen. Inhaled NO was then administered in concentrations of 5, 10, 20, 30, 40, 60, and 80 parts per million in random order according to a Latin square design. After meconium instillation, NO inhalation led to significant increases in mean arterial saturation of between 18 and 24 percentage points at all doses, and to statistically significant decreases in pulmonary arterial pressure (from 6.0 kPa, SD 1.3 to 5.1 kPa, SD 1.5, P < 0.01) and pulmonary vascular resistance index (from 0.033 kPa/mL/min/kg, SD 0.003 to 0.029 kPa/mL/min/kg, SD 0.003, P < 0.01). Systemic blood pressure, cardiac index and systemic vascular resistance index did not change. The ratio between pulmonary and systemic vascular resistances fell, therefore, from a mean of 0.54 (SD 0.18) to 0.46 (SD 0.14). The effects of NO inhalation after meconium aspiration were qualitatively different to the effects during aveolar hypoxia, in that there was a lesser fall in the PAP and PVR1 and a significant increase in SaO₂. These results suggest that inhaled NO may be beneficial in meconium aspiration syndrome in human neo-nates, improving oxygenation by decreasing extrapulmonary shunting and by improving ventilationiperfusion ratios. Pediatr Pulmonol. 1995; 20:27–33 . © 1995 Wiley-Liss, Inc.     

先天性心脏病重度肺动脉高压对腺苷的急性反应

目的: 探讨先天性心脏病（CHD）并发重度肺动脉高压（PAH）患者对腺苷的急性血流动力学反应。方法: 对25例CHD并发严重PAH患者采用腺苷进行急性肺血管扩张试验,检测其血流动力学指标变化。结果: 25例患者中,仅7例患者达到最大剂量无不良反应。给予腺苷后,肺动脉压力和主动脉压力均显著降低（P<0.05）,股动脉血氧饱和度,肺血管阻力,肺循环/体循环血流量比值,肺动脉/主动脉平均压比值,肺血管阻力/体循环阻力比值（Rp/Rs）均无明显变化。没有患者肺动脉平均压降至40 mmHg以下。12例患者肺血管阻力和Rp/Rs降低10%以上,与另外13例患者比较,二者在年龄,肺动脉压力,肺动脉/主动脉平均压比值,肺循环/体循环血流量比值,肺血管阻力和Rp/Rs等方面均无明显差异。结论: 在CHD并发重度PAH患者中,采用腺苷进行急性肺血管扩张试验可引起肺动脉和体循环压力同步降低,而对肺血管阻力无明显影响。     

Regression of myocardial fibrosis in hypertensive heart disease: diverse effects of various antihypertensive drugs

OBJECTIVE: In left ventricular hypertrophy (LVH) due to systemic hypertension, myocardial fibrosis is an important determinant of pathologic hypertrophy. Therefore, it is most relevant to utilize an antihypertensive regimen that permits a regression in myocardial fibrosis along with blood pressure normalization and regression of LVH. METHODS: To address this issue we examined 60 Sprague-Dawley rats. We treated 16-week-old rats having established LVH and myocardial fibrosis due to 8-week renovascular hypertension (RHT) with either 6 mg/kg/day zofenopril (ZOF), 30 mg/kg/day nifedipine (NIF) or 40 mg/kg/day labetalol (LAB) for 12 weeks. Systolic arterial pressure (SAP, mmHg), left ventricular/body weight ratio (LV/BW, mg/g), and left and right ventricular collagen volume fractions (LVCVF, RVCVF, %) were obtained and compared with age/sex matched untreated rats with RHT and sham-operated controls. RESULTS: In RHT, SAP was significantly elevated compared with controls (188+/-11 vs. 125+/-5 mmHg; P<0.001) while in each treated group SAP was normalized. LV/BW was significantly increased in RHT (2.61+/-0.12 mg/g; P<0.00001) while in each treated group LVH was completely regressed (P<0.002 vs. untreated RHT) with LV/BW values comparable to controls (1.82+/-0.03 mg/g) irrespective of the utilized antihypertensive agent. In untreated RHT, myocardial fibrosis was present in the left (LVCVF: 12.3+/-1.9%; P<0.0005 vs. 4.5+/-0.2% of controls) and right ventricles (RVCVF: 20.6+/-2.5%; P<0.00005 vs. 8.8+/-0.4% of controls). In rats treated with ZOF or NIF, LVCVF was significantly reduced to 5.6+/-0.4 and 5.4+/-0.6%, respectively (P<0.005 vs. untreated RHT), and RVCVF was decreased as well (ZOF: 11.0+/-0.9%; NIF: 10.4+/-2.4%; P<0.007 vs. untreated RHT) where no significant difference to controls remained. In contrast, treatment with LAB did not affect myocardial fibrosis where LVCVF was 9.3+/-1.3% and RVCVF was 19.8+/-2.8%, i.e., remained significantly elevated compared with controls (P<0.007). CONCLUSIONS: In rats with renovascular hypertension and hypertensive heart disease that included LVH and fibrosis, equipotent doses of ZOF, NIF, and LAB normalized arterial pressure associated with regression of LVH while only ZOF and NIF were found to regress myocardial fibrosis.     

Continuous veno-venous haemofiltration in the treatment of severe acute pancreatitis: 6-year experience

Background. Continuous veno-venous haemofiltration (CVVH) could be reasonable for attenuation of systemic complications in severe acute pancreatitis (SAP). The aim of the study was implementation and feasibility assessment of the CVVH in the treatment protocol of SAP. Patients and methods. CVVH was applied to 111 SAP patients during 2000–2005. APACHE II, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), serum lipase, C-reactive protein (CRP), complication rate and main outcomes were analysed comparing two periods. Results. Overall, 39 patients corresponded to Balthazar grade E SAP and 72 patients to necrotizing SAP (NSAP), with an average APACHE II score of 7 and 8.5, respectively, on admission. CVVH was started within 48 h in 82% of patients. Duration of CVVH was significantly augmented in NSAP patients during the routine period, comprising 92 h (p=0.006). The clinical presentation of SIRS and MODS was similar in both periods, with more initial pulmonary dysfunctions in NSAP (p=0.048). Peripancreatic infection decreased in the routine period; surgical interventions were performed in 34.8% vs 72.4% of patients. Hospital stay comprised on average 15.9 days for grade E SAP and 29.4 days for NSAP in the routine period, with overall mortality of 10.26% and 30.5%, respectively. Discussion. Application of CVVH in the treatment protocol of SAP is obscure due to relative invasiveness, a poorly understood mechanism of action and scarce clinical experience. We conclude that early pre-emptive application of CVVH is safe and feasible in the treatment of SAP. Duration of the procedure seems to be essential. Randomized clinical trials are justified. Our results are in favour of clinical application of CVVH in the treatment of SAP.     

The study of fecal-Escherichia coli peritonitis-induced septic shock in a neonatal pig model

Peritonitis-induced septic shock in the neonate is associated with a high mortality. Because there exists no clinically relevant model to study resuscitation of these patients, a model using the neonatal pig was developed. After arterial and central venous cannulation, and placement of a left pulmonary-artery thermodilution catheter, 12 anesthetized neonatal pigs were "resuscitated" with fluids (5% albumin in lactated Ringer's solution at 15 ml/kg/hr), antibiotics, and correction of acidemia. The pigs were divided into two groups: a control group (n = 5), which was not subjected to peritonitis and which was killed after 6 hours of monitoring, and a septic group (n = 7), which was inoculated with an intraperitoneal injection of sterile pig feces and Escherichia coli and was monitored until death (mean survival time (S.D.) 546(159) minutes). Serial measurements of hemodynamic and laboratory data were obtained. While pigs in the control group showed no significant changes in these data as measured against time, the pigs in the experimental group showed an early transient rise in cardiac index which was significant (p less than .05) and which was followed by a steady decline in cardiac index until death. These changes in cardiac index were accompanied by a continuous decline in mean arterial pressure, central venous pressure, pulmonary artery pressure, and systemic vascular resistance index, while pulmonary vascular resistance index showed a gradual continuous rise. The observed changes in hemodynamic and laboratory data mimic those anticipated in the human neonate with peritonitis-induced septic shock. This model proves reliable and reproducible, and shows promise as a tool to study the resuscitation of neonates with septic shock.     

Enalaprilat, a new parenteral angiotensin-converting enzyme inhibitor: rapid changes in systemic and coronary hemodynamics and humoral profile in chronic heart failure

Systemic and coronary hemodynamic, metabolic and humoral effects of a new intravenous angiotensin-converting enzyme inhibitor, enalaprilat, were evaluated in 14 patients with chronic heart failure. Onset of hemodynamic action occurred within 15 minutes and persisted for 6 hours. At the time of peak effect, there was a significant reduction in mean arterial pressure (-21%) and pulmonary capillary wedge pressure (-33%). Systemic vascular resistance decreased by 32% and stroke volume index increased by 20%. These systemic hemodynamic changes indicate improved left ventricular function. There was a substantial sustained reduction in rate-pressure product initially without a change in coronary sinus blood flow or myocardial oxygen consumption. There was also reduced myocardial oxygen extraction and augmented coronary sinus oxygen saturation at 30 minutes and 1 hour. In three patients, abnormal myocardial lactate extraction, present before enalaprilat, changed to uptake after enalaprilat, indicating amelioration of myocardial ischemia that was not clinically manifest. Systemic catecholamine levels and myocardial catecholamine balance did not change. Plasma renin activity increased and plasma aldosterone decreased. These findings suggest that enalaprilat produces inhibition of the angiotensin-converting enzyme and consequent beneficial systemic hemodynamic changes in heart failure. In some patients with heart failure, silent myocardial ischemia at rest can occur and can be alleviated with enalaprilat. Decreased myocardial oxygen extraction, increased coronary sinus oxygen saturation and lack of expected decrease in coronary sinus blood flow despite reduced rate-pressure product suggest transient coronary vasodilation by enalaprilat.     

Lidocaine therapy in awake endotoxemic Yucatan minipigs. II. Hepatosplanchnic metabolism

Reductions in hepatosplanchnic blood flow and oxygen delivery contribute to the hepatic metabolic dysfunction observed in endotoxemia. Through its membrane-stabilizing activity, systemic lidocaine therapy may modify visceral hemodynamics and preserve hepatocellular metabolic function in endotoxic shock. Twelve 50-kg pigs were surgically fitted with jugular, portal, hepatic venous and carotid arterial catheters, and hepatic arterial and portal venous flow cuffs to quantitate portosystemic and transhepatic kinetics. Seventy-two hours later they were placed in slings, and following a 3-h control period were infused with Escherichia coli endotoxin (Difco 055:B5) at 15 micrograms/kg/h for 6 h. Eight were controls and four received a primed (2 mg/kg) continuous infusion (2 mg/kg/h) of lidocaine 1 h following the initiation of endotoxin infusion. Hepatosplanchnic blood flow was relatively unaffected by lidocaine infusion. In both untreated and treated pigs, hepatic arterial flow decreased by 25-30%, portal venous flow fell by approximately 60%, and hepatic venous flow was reduced by 50%. Following 2 h of endotoxin infusion, net splanchnic glucose uptake was increased significantly in lidocaine-treated pigs, but not in untreated endotoxemic animals. Transhepatic lactate kinetics were unaffected by treatment, but net hepatic pyruvate uptake in the lidocaine-treated group increased as compared to the untreated group by 140 min postendotoxin, being significantly greater at 220, 280, and 320 min. Hepatic oxygen input was significantly reduced by 25-30% in both groups within 1 h of the onset of endotoxemia, but hepatic oxygen extraction efficiency increased two-to-three-fold, thereby maintaining net hepatic oxygen uptake. Despite the maintenance of hepatic oxygen uptake and improved hepatic pyruvate extraction in lidocaine treated endotoxemic pigs, no significant improvements in glucose homeostasis were incurred, leading to the conclusion that lidocaine therapy offered few significant advantages in the treatment of overall metabolic derangements during acute endotoxemia.     

Hemodynamic variables and plasma levels of PGI2, TXA2 and IL-6 in a porcine model of recurrent endotoxemia.

The pulmonary and systemic hemodynamic effects of recurrent endotoxemia were studied in pigs over a 48-hr period. Six pigs of the test group were given 0.5 micrograms/kg of an E. coli endotoxin (WO111: B4) over 60 min at the beginning and in the middle (22 hr) of the experiment. Three pigs given the same amount of physiological saline solution served as controls. The hemodynamic response to the first LPS injection was characterized by severe pulmonary hypertension, a significant increase in systemic vascular resistance, and a marked decrease in cardiac output. Circulating TxB2 levels were higher than those of 6-keto-PGF1 alpha levels, so that the first response to LPS is influenced by the vasoconstrictive actions of TxA2. With the second LPS application, the pulmonary response was attenuated, although a significant increase of pulmonary artery pressure and pulmonary vascular resistance occurred. Once again systemic vascular resistance rose and cardiac output decreased, but this time plasma levels of 6-keto-PGF1 alpha were greater than those of TxB2. Toward the end of the experiment, we noted the progressive onset of a hyperdynamic and hypotensive state. Systemic vascular resistant index decreased to 50% of the baseline value. IL-6, a cytokine of systemic importance during the course of septic shock, markedly and significantly peaked after each LPS injection. Circulating plasma levels in response to recurrent endotoxemia are described.     

Cardiovascular and pulmonary effects of thromboxane B2 in the dog.

The hemodynamic properties of thromboxane B2 (TxB2), a product of prostaglandin endoperoxide metabolism, have not been thoroughly described. TxB2 is a bronchoconstrictor, but its effects on the systemic circulation and circulating platelets are unknown. Its precursor, thromboxane A2(TxA2), is a potent vasoconstrictor as well as a platelet-aggregating agent. Using intact anesthetized dogs, we investigated the effects of TxB2 on pulmonary artery pressure (PAP), airway pressure (AP), systemic arterial pressure (SAP), and myocardial contractility (MC). Vascular responses were evaluated in relation to changes in platelet population and aggregability. Intravenous TxB2 (25 and 50 micrograms/kg) increased AP (mean 62% and 69%) and PAP (50% and 86%), respectively, whereas SAP and MC responses were inconsistent. Left ventricular injections (25 micrograms/kg) also increased AP (36%) and PAP responses were inconsistent. Left ventricular injections (25 micrograms/kg) also increased AP (36%) and PAP (36%). Intraventricular administration of TxB2 produced a consistent elevation of SAP (10%) with a concomitant fall in MC (11%). These vascular responses were not consistent with alterations in platelet number or aggregability. A tachyphylactic response to TxB2 developed in AP and PAP at both dose levels and with both routes of administration. Intravenous and intraventricular TxB2 (25 micrograms/kg) produced a parallel decreasing response in PAP, suggesting the possible saturation of TxB2 binding sites or the depletion of a catabolic enzyme in the lung.     

Oxygen delivery and utilization during rapidly fatal septic shock in rats

Oxygen delivery and utilization were studied in a rapidly fatal model of rat peritonitis. Cecal ligation and perforation induced peritonitis and septic shock in five animals. Five animals served as sham-operated controls. Arterial pressure, central venous pressure, cardiac index, hemoglobin, plasma colloid osmotic pressure, arterial blood lactate concentration, and arterial and central venous oxygen saturation were sequentially measured over 5 hr. In septic animals, decreases in mean central venous pressure were associated with hemoconcentration and decreases in plasma colloid osmotic pressure from 16.3 +/- 0.8 to 12.2 +/- 0.1 mmHg (P less than 0.05). The cardiac index decreased from 359 +/- 35 to 166 +/- 25 ml/kg/min (P less than 0.001), and arterial lactate increased from 0.2 +/- 0.1 to 2.1 +/- 0.4 mmol (P less than 0.001). However, oxygen consumption was maintained secondary to increases in systemic oxygen extraction. Arterial lactate concentration was inversely correlated with systemic oxygen delivery and central venous oxygen saturation (r = -0.68, P less than 0.05 and r = -0.71, P less than 0.001, respectively). These observations during lethal peritonitis suggest that hypovolemia is associated with increases in microvascular permeability, although the concomitant influence of intravascular pooling cannot be excluded. Decreases in systemic perfusion appear to account for critical oxygen deficits and lactic acidosis. The increases in systemic oxygen extraction imply that cellular oxygen utilization is maintained during lethal septic shock.