Cytokine removal and cardiovascular hemodynamics in septic patients with continuous venovenous hemofiltration

Objectives: To determine whether continuous venovenous hemofiltration leads to extraction of tumor necrosis factor alpha (TNFα) and cytokines from the circulation of critically ill patients with sepsis and acute renal failure and to quantitate the clearance and the removal rate of these cytokines and their effect on serum cytokine concentrations. Design: Prospective, controlled study in patients with continuous venovenous hemofiltration (24 l/24 h) using a polysulphone membrane in patients with acute renal failure. Patients: 33 ventilated patients with acute renal failure of septic (n = 18) and cardiovascular origin (n = 15) were studied. Interventions: Hemodynamic monitoring and collection of blood and ultrafiltrate samples before and during the first 72 h of continuous hemofiltration. Measurements and main results: Cardiovascular hemodynamics (Swan-Ganz catheter), Acute Physiology and Chronic Health Evaluation II score, creatinine, electrolytes, and blood urea nitrogen were recorded daily. Cytokines (TNFα, TNFα-RII, interleukin (IL) 1β , IL1RA, IL2, IL2R, IL6, IL6R, IL8, IL10) were measured in prefilter blood and in ultrafiltrate immediately preceding and 12, 24, 48, and 72 h after initiating continuous venovenous hemofiltration (CVVH). Septic patients showed elevated cardiovascular values for cardiac output (7.2 ± 2.1 l/min), cardiac index (4.2 ± 1.3 l/min per m²), and stroke volume (67 ± 23 ml) and reduced values for systemic vascular resistance (540 ± 299 dyn · s · cm^{− 5}). All hemodynamic values normalized within the first 24 h after initiating CVVH treatment. TNFα was 1833 ± 1217 pg/ml in septic patients and 42.9 ± 6.3 pg/ml in nonseptic patients (p < 0.05) prior to CVVH. TNFα was detected in ultrafiltrate but did not decrease in blood during treatment with CVVH. There was no difference in IL 1β between septic (3.8 ± 1.9 pg/ml) and nonseptic patients (1.7 ± 0.5 pg/ml). No significant elimination of cytokines was achieved in the present study by CVVH treatment. Conclusions: These findings demonstrate that CVVH can remove TNFα and special cytokines from the circulation of critically ill patients. Cardiovascular hemodynamics seemed to improve in septic patients after induction of hemofiltration treatment, although there was no evidence that extracorporeal removal of cytokines achieved a reduction in blood levels. The study indicates that low volume continuous hemofiltration with polysulphone membranes in patients with acute renal failure is not able to induce significant removal of cytokines. Received: 12 February 1996 Accepted: 27 November 1996     

连续静-静脉血液滤过对多脏器功能障碍综合征患者炎症介质的影响

目的 应用连续静—静脉血液滤过(CVVH)技术，探讨对多器官功能障碍综合征(MODS)患者炎症介质水平的影响。方法 17例MODS患者经右侧股静脉插管留置单针单腔导管，行CVVH模式治疗。于CVVH治疗前后，检测血液电解质，肾功能，于CVVH治疗前和治疗后1、2、4、6、8h抽取静脉血液检测炎症介质，其中采用EUSA法测定有关炎症介质因子。结果 17例患者CVVH后血清BUN，Ser，K^ 均呈下降趋势(P＜0．05)，血浆TNF-α，IL-6，IL-8水平均降低。结论 CVVH能清除MODs患者血浆多种炎症介质因子，并可降低BUN，Cr，K^ 水平。     

Metabolic effects of citrate- vs bicarbonate-based substitution fluid in continuous venovenous hemofiltration: A prospective sequential cohort study

Background

Studies investigating the metabolic effects of citrate-based substitution fluids are lacking. This study aims to compare the effect of citrate- vs bicarbonate-based substitution fluid used during continuous venovenous hemofiltration (CVVH) for acute kidney injury on acid-base balance and electrolytes in critically ill patients.

Methods

This was a prospective sequential cohort study in patients with a contraindication for systemic anticoagulation. The first cohort was treated by bicarbonate-based CVVH (n = 10) and the second cohort was treated by CVVH with citrate-based substitution fluid (n = 19). Flow of the latter was coupled to blood flow, and ionized calcium concentrations were monitored and kept constant by calcium-glubionate infusion.

Results

No major differences between the 2 groups were found in baseline acid-base parameters. In both groups, arterial pH increased after initiation of treatment and normalized on the average within 18 hours in either group. No differences were found in bicarbonate concentrations. Electrolyte control was comparable for the groups.

Conclusion

Citrate-based substitution fluid is comparable to bicarbonate-based substitution fluid during CVVH in critically ill patients with acute kidney injury, concerning acid-base balance and electrolyte control. This implies complete conversion of citrate to bicarbonate in the patients studied.     

Pharmacokinetics of milrinone in patients with congestive heart failure during continuous venovenous hemofiltration

Objective: To evaluate the pharmocokinetics of intravenous milrinone in patients with severe congestive heart failure during continuous venovenous hemofiltration (CVVH). Design: Prospective study of patients with congestive heart failure admitted to the intensive care unit (ICU). Setting: ICU between September 1997 and August 1999. Patients and methods: Six patients with severe congestive heart failure during CVVH: all patients received a continuous infusion of milrinone of 0.25 μg · kg^{− 1}· min^{− 1}. The hemodynamics and plasma concentration of milrinone were measured before and after the infusion. Pharmacokinetics were analyzed with one-compartment model featuring constant rate infusion. Results: The steady-state concentration (Css) was 845 ± 135 (mean ± SD) ng/ml, and the half-life time (t_1/2) was 20.1 ± 3.3 h. Cardiac index and stroke volume index after the infusion of milrinone increased significantly compared with pre-infusion levels. Other hemodynamic parameters did not change significantly. All patients died within 1 month after the injection of milrinone because of severe forms of arrhythmia, such as ventricular tachycardia and ventricular fibrillation. Conclusions: We found that the mean Css and the mean t_1/2 of milrinone in subjects during CVVH were much higher and longer than those previously reported for subjects with normal renal function. It is therefore essential to adjust the dose or modify the dosing interval of milrinone during renal replacement therapy for patients with severe congestive heart failure. However, further studies are needed to determine the details of pharmacokinetics of milrinone and therapeutic procedures for patients with severe heart failure during CVVH. Received: 1 December 1999 Final revision received: 9 March 2000 Accepted: 11 April 2000     

Pharmacokinetics and the most suitable dosing regimen of fluconazole in critically ill patients receiving continuous hemodiafiltration

Objective To evaluate fluconazole pharmacokinetics and the dosage best suited to maintain effective plasma concentration in patients with continuous hemodiafiltration.Design and setting Prospective study in the general intensive care unit of a university hospital.Patients Four critically ill patients being treated with fluconazole and receiving continuous hemodiafiltration.Interventions Fluconazole was administered at three dosing regimens: 200 and 400 mg every 24 h, 400 mg every 12 h, and 800 mg every 24 h.Measurements and results The following pharmacokinetic variables for fluconazole were obtained: The mean volume distribution of steady state dosed at 400 mg every 12 h and 800 mg every 24 h were 0.55±0.23 and 0.71±0.16 l/kg, half-life of the elimination phase 8.08±0.83 and 9.12±0.75 h, total body clearance of fluconazole 1.14±0.44 and 0.98±0.20 ml/kg per minute, respectively. None of the dosing regimens reached the effective plasma trough concentration of fluconazole; however, simulation study found the recommended dose.Conclusions Continuous hemodiafiltration is highly effective in removing fluconazole from circulation. We recommend fluconazole to be dosed at 500–600 mg intravenously every 12 h in patients receiving hemodiafiltration. This dosing regimen resulted in adequate trough plasma levels for systemic fungal infection.     

连续性肾脏替代疗法治疗危重症患者的护理

目的 探讨连续性肾脏替代疗法治疗危重症患者的应用及临床护理措施.方法 选取2009年10月至201 1年6月于本院进行治疗的l00例危重症患者为研究对象,对其实施护理措施,将连续性肾脏替代疗法治疗前后患者的生化指标进行比较分析.结果 连续性肾脏替代疗法治疗后患者的生化指标较治疗前均有明显改善.结论 在连续性肾脏替代疗法治疗危重症患者的过程中实施有效、全面的护理能够很大程度上改善患者的生命指标,提高重症患者的存活率,值得在临床开展应用.     

Pharmacokinetics and dosing regimen of meropenem in critically ill patients receiving continuous venovenous hemofiltration

OBJECTIVE: To study the pharmacokinetics of meropenem in critically ill patients with acute renal failure receiving continuous venovenous hemofiltration (CWHF). DESIGN: Prospective, open-labeled study. SETTING: Medical intensive care unit of the University Medical Center Utrecht. PATIENTS: Five critically ill patients receiving CWHF for acute renal failure treated with meropenem for documented or suspected bacterial infection. INTERVENTION: All patients received meropenem (500 mg) administered intravenously every 12 hrs. Plasma samples and ultrafiltrate aliquots were collected during one dosing interval. MEASUREMENTS AND RESULTS: Mean age and body weight of the patients studied were 46.6 yrs (range, 28-61 yrs) and 85.8 kg (range, 70-100 kg), respectively. The following pharmacokinetic variables for meropenem were obtained: mean peak plasma concentration was 24.5 +/- 7.2 mg/L, mean trough plasma concentration was 3.0 +/- 0.9 mg/L, mean terminal elimination half-life was 6.37 +/- 1.96 hrs, mean total plasma clearance was 4.57 +/- 0.89 L/hr, mean CWHF clearance was 1.03 +/- 0.42 L/hr, mean nonrenal clearance was 3.54 +/- 1.06 L/hr, and mean volume of distribution was 0.37 +/- 0.15 L/kg. CONCLUSION: In critically ill patients with acute renal failure, nonrenal clearance became the main elimination route. CWHF substantially contributed to the clearance of meropenem (23% of mean total plasma clearance). We recommend meropenem to be dosed at 500 mg intravenously every 12 hrs in patients receiving CWHF, according to our operational characteristics. This dosing regimen resulted in adequate trough plasma levels for susceptible microorganisms.     

局部枸橼酸钠抗凝的连续性静脉-静脉血液滤过治疗中患者补钙速度的研究

目的探讨超滤液中钙的清除率,并明确在采用局部枸橼酸钠抗凝的连续性静脉-静脉血液滤过（CVVH）治疗期间,其是否可以作为患者补钙速度的参考指标。 方法55例需要连续性肾脏替代治疗（CRRT）的高危出血风险患者,均接受CVVH治疗模式,拟采取局部枸橼酸钠抗凝（4%枸橼酸钠200 ml/h）。第一阶段采用完全后稀释方式输入,检测血总钙及超滤液总钙浓度,观察超滤液中钙的清除率。第二阶段将正常组和低钙组患者均随机分为全后稀释组、前后1:1稀释组、全前稀释组。在CVVH期间,根据第一阶段实验得出的钙清除比例等量补充钙剂。常规每4 h监测体内血离子钙及滤器后离子钙浓度,并在上机前、上机后6 h和12 h分别检测患者血总钙、超滤液总钙及血离子钙的浓度。 结果（1）治疗时间：每例次平均治疗时间（21.2±5.6）h,无一例患者因体外回路凝血而终止CVVH治疗;（2）第一阶段15例患者超滤液总钙浓度与血总钙浓度比例为85%,其中正常组钙清除率为84.5%,低钙组钙清除率为85.5%,正常组和低钙组的钙清除率与总体钙清除率3组间无统计学差异（F=0.8484,P>0.05）;（3）第二阶段正常组30例患者理论计算所得超滤液钙浓度与实际检测所得超滤液钙浓度比较,全后稀释组、前后1:1稀释组、全前稀释组结果均无统计学差异（t=0.1637,1.103,0.04;P均>0.05）,第二阶段低钙组10例患者理论计算所得超滤液钙浓度与实际检测所得超滤液钙浓度比较,全后稀释组、前后1:1稀释组、全前稀释组结果均无统计学差异（t=0.1968,2.402,0.1818;P均>0.05）;（4）第二阶段正常组30例患者CVVH模式治疗前、治疗后6 h和12 h的体内血总钙浓度比较和血离子钙浓度比较,结果均无统计学差异（F=2.5690,2.8930;P均>0.05）,第二阶段低钙组10例患者CVVH模式治疗前、治疗后6 h和12 h的体内血总钙浓度比较和血离子钙浓度比较,结果均无统计学差异（F=0.7124,1.080;P均>0.05）;（5）CVVH模式治疗期间,正常组30例患者没有血钙异常发生,低钙组10例患者没有出现低钙血症的临床表现且治疗期间体内血离子钙水平正常。 结论在采取局部枸橼酸钠抗凝的CVVH治疗期间,可以根据患者血总钙浓度以及置换液前后补充方式的不同,计算出理论上患者的血钙清除率,并将其作为CVVH治疗时补钙速度的参考依据。     

The use of different buffers during continuous hemofiltration in critically ill patients with acute renal failure

Objective: To determine the impact of different hemofiltration (HF) replacement fluids on the acid-base status and cardiovascular hemodynamics in patients with acute renal failure (ARF) and continuous veno-venous hemofiltration (CVVH).¶Design: Prospective, cohort study.¶Setting: Intensive Care Unit of the Heinrich Heine University Hospital, Düsseldorf, Germany.¶Subject and methods: One hundred and thirty-two critically ill patients with acute renal failure and continuous veno-venous HF were studied. Fifty-two patients were subjected to lactate-based (group 1), and 32 to acetate-based hemofiltration (group 2)while 48 (group 3) were treated with bicarbonate-based buffer hemofiltration fluid. Fifty-seven had a septic, and 75 a cardiovascular, origin of the ARF. Creatinine, blood urea nitrogen (BUN), serum bicarbonate, arterial pH, lactate and Apache II scores were noted daily.¶Main results: The mean CVVH duration was 9.8 ± 8.1 days, mortality was 65 %. No difference was present between the groups under investigation with regard to the main clinical parameters. Lactate- and bicarbonate-based hemofiltration led to significantly higher serum bicarbonate and arterial pH values as compared to the acetate-based hemofiltration. Serum bicarbonate values at 48 h after the initiation of CVVH treatment were 25.7 ± 3.8 mmol/l (p < 0.001) in group 1, 20.6 ± 3.1 mmol/l in group 2 and 23.3 ± 3.9 mmol/l (p < 0.001) in group 3. While a lack of increase in serum bicarbonate and arterial pH was correlated to poor prognosis in lactate- and bicarbonate-based hemofiltration, no such observation was made in acetate-based hemofiltration. Cardiovascular hemodynamics were superior in patients treated with lactate- and bicarbonate-based buffer solution as compared to those treated with acetate-based buffer solution.¶Conclusions: The degree of correction of acidosis during hemofiltration was determined by patient outcome in patients treated with lactate- and bicarbonate-based buffer solutions, but not in patients receiving acetate-buffered solution. Bicarbonate and lactate-based buffer solutions were found to be superior to acetate-based replacement fluid.     

Enhanced fluid management with continuous venovenous hemofiltration in pediatric respiratory failure patients receiving extracorporeal membrane oxygenation support

Background/purpose  Children receiving extracorporeal membrane oxygenation (ECMO) for respiratory failure can have significant fluid overload and renal insufficiency. Addition of inline continuous venovenous hemofiltration (CVVH) could provide additional benefits in fluid management compared to use of standard medical therapies with ECMO. Methods  Patients with pediatric respiratory failure receiving ECMO with CVVH were case-matched to similar patients receiving ECMO without CVVH to compare fluid balance, medication use, and clinical outcomes. Results  Twenty-six of eighty-six patients with pediatric respiratory failure on ECMO (30%) received CVVH for >24 h (median 7.5 days on CVVH). Survival was not significantly different between patients receiving CVVH and those who did not receive CVVH (P = 0.51). For ECMO survivors receiving CVVH, overall fluid balance was less than that in non-CVVH survivors (median 25.1 ml kg⁻¹ day⁻¹; range −40.2 to 71.2 vs. 40.2, 1.1 to 134.9; P = 0.028). Time to desired caloric intake was faster in patients receiving CVVH (1 day, 1–5) than in patients who did not receive CVVH (5 days; 1–11; P < 0.001). Patients receiving CVVH–ECMO also received less furosemide (0.67 vs. 2.11 mg kg⁻¹ day⁻¹; P = 0.009). Conclusions  Use of CVVH in ECMO was associated with improved fluid balance and caloric intake and less diuretics than in case-matched ECMO controls.     

多器官功能障碍综合征患者细胞因子释放规律及CVVH干预治疗对其预后的影响

目的 观察多器官功能障碍综合征(MODS)患者3种细胞因子的释放规律及连续性静脉静脉血液滤过(CVVH)干预治疗对其预后的影响。方法 选择50例符合MODS诊断标准的住院患者，随机分为两组，治疗组常规治疗加CVVH。两组患者均于入院时、12、24、48、72、96和168h分别留取血样，治疗组于CVVH前后分别留取血样、滤液样数份置零下40℃冰冻待验。结果 治疗组TNF—α、IL—1β分泌高峰在病程初中期，对照组在病程后期，CVVH，可使其分泌高峰提前，但对3种细胞因子(ck)血浆浓度无明显影响。所有滤液中可检出3种细胞因子，治疗组血流动力学及氧合功能改变明显优于对照组，病死率及预计死亡率较对照组低。结论 在MODS患者病程早期做CVVH治疗，可以减轻或部分阻断细胞因子的过度释放，改善了患者赖以生存的内环境和预后。     

连续性静脉血液滤过治疗重度充血性心力衰竭临床效果观察

目的 评价不同原因的重度充血性心力衰竭应用连续性静脉血液滤过(CVVH)治疗的疗效.方法 31例为无尿或少尿的重度充血性心力衰竭(心功能NYHA分级Ⅳ)患者,均给予床旁CVVH治疗,1次/d,每次6～10 h,治疗前、后测定肾功能(BUN、Cr)、电解质(K+、Na+、Cl-)、肝功能(AST)、左心室射血分 数(LVEF)、平均动脉压(MBP)、心率.每天记录进出量.结果 24例临床症状明显好转,其中9例肾功能 完全恢复正常,生存率达77.42%(24/31).1例因故终止治疗,6例1周内死亡.结论 对于无尿或少尿的重度充血性心力衰竭在药物治疗同时行连续性静脉血液滤过的综合治疗,可取得明显疗效,降低病死率,是治疗重度充血性心力衰竭的有效方法 .     

Pharmacokinetics of cefpirome in critically ill patients with renal failure treated by continuous veno-venous hemofiltration

Objective: To study the cefpirome pharmacokinetics of patients with sepsis and multiple organ failure treated with CVVH. Design: Measurements of serum and ultrafiltrate (UF) concentrations and in vitro sensitivity testing of isolated micro-organisms. Setting: University hospital-based, single ICU. Patients: Six critically ill CVVH- dependent patients with sepsis and multiple organ dysfunction syndrome in need of antimicrobial therapy. Age range: 60–75 years; APACHE II score for severity of illness on admission: 19–30. One patient survived. Interventions: Cefpirome i. v. was started at 2 g in 30 min, then continued 1 g i. v. b. i. d. Measurements: The UF rate was 27 ± 7 ml/min on day 1 and 34 ± 2 ml/min on day 2. Serum and ultrafiltrate samples were measured by a validated high performance liquid chromatography assay. Volume of distribution: 23 · 5(SD ± 4 · 6) l. Total cefpirome clearance was 32 ± 6 · 3 ml/min; cefpirome CVVH clearance (Cl_CVVH): 17 ± 4.2 ml/min; mean serum half-life (t^1/2): 8.8 ± 2.3 h; mass transfer on day 1: 660 ± 123 mg/12 h (33 ± 6 % of administered dose)and day 2: 642 ± 66 mg/12 h (64 ± 7 %). Estimated sieving coefficient (Cl_CVVH/UF rate): 64 ± 11 %. In vitro sensitivity of isolated microbes was excellent except for two non-sensitive enterococci and Candida spp. Conclusions: The sieving coefficient (64 %) indicates that a substantial fraction of the drug is not filtered; clearance by pathways other than CVVH mounted to 50 % of the total clearance and increased on day 2, indicating that the dosing schedule used is appropriate for this setting. Cefpirome appeared to be safe in these patients and effective for most of the nosocomial microbial isolates. During more than 90 % of the time, serum levels were maintained above killing concentrations for susceptible micro-organisms. Received: 23 July 1999 Accepted: 19 October 1999     

Mass transfer, clearance and plasma concentration of procalcitonin during continuous venovenous hemofiltration in patients with septic shock and acute oliguric renal failure

Objectives

To measure the mass transfer and clearance of procalcitonin (PCT) in patients with septic shock during continuous venovenous hemofiltration (CVVH), and to assess the mechanisms of elimination of PCT.

Setting

The medical department of intensive care.

Design

A prospective, observational study.

Patients

Thirteen critically ill patients with septic shock and oliguric acute renal failure requiring continuous venovenous postdilution hemofiltration with a high-flux membrane (AN69 or polyamide) and a 'conventional' substitution volume (< 2.5 l/hour).

Measurements and main results

PCT was measured with the Lumitest PCT Brahms^® in the prefilter and postfilter plasma, in the ultrafiltrate at the beginning of CVVH (T0) and 15 min (T15'), 60 min (T60') and 6 hours (T6h) after setup of CVVH, and in the prefilter every 24 hours during 4 days. Mass transfer was determined and the clearance and the sieving coefficient were calculated according to the mass conservation principle. Plasma and ultrafiltrate clearances, respectively, at T15', T60' and T6h were 37 ± 8.6 ml/min (not significant) and 1.8 ± 1.7 ml/min (P < 0.01), 34.7 ± 4.1 ml/min (not significant) and 2.3 ± 1.8 ml/min (P < 0.01), and 31.5 ± 7 ml/min (not significant) and 5 ± 2.3 ml/min (P < 0.01). The sieving coefficient significantly increased from 0.07 at T15' to 0.19 at T6h, with no difference according to the nature of the membrane. PCT plasma levels were not significantly modified during the course of CCVH.

Conclusions

We conclude that PCT is removed from the plasma of patients with septic shock during CCVH. Most of the mass is eliminated by convective flow, but adsorption also contributes to elimination during the first hours of CVVH. The effect of PCT removal with a conventional CVVH substitution fluid rate (<2.5 l/hour) on PCT plasma concentration seems to be limited, and PCT remains a useful diagnostic marker in these septic patients. The impact of high-volume hemofiltration on the PCT clearance, the mass transfer and the plasma concentration should be evaluated in further studies.     

Relation between indocyanine green (ICG) plasma disappearance rate and ICG blood clearance in critically ill patients

Objective In contrast to indocyanine green (ICG) blood clearance, the plasma disappearance rate (PDR) of ICG does not require absolute ICG blood concentrations and today can be assessed transcutaneously. In this study, we analyzed the relation between ICG disappearance rate and ICG blood clearance as parameters of liver function in critically patients. Design Observational, clinical study. Retrospective analysis. Setting Operative intensive care unit of a university hospital. Patients 209 patients (139 male, 70 female, age 10–88 years, 53 ± 19 years) who underwent liver function monitoring for clinical indication. Patients suffered from sepsis (n = 99), acute respiratory distress syndrome (n = 31), severe head injury (n = 38), hemorrhagic shock (n = 19), intracranial hemorrhage (n = 19), and cerebral infarction (n = 3). All patients were sedated and mechanically ventilated via an endotracheal tube. Measurements and results All patients were monitored by the transpulmonary double-indicator (thermo-dye dilution) technique using a thermistor and calibrated fiber-optic system (Pulsiocath 4F, PV 2024L, Pulsion Medical Systems, Munich, Germany). For each measurement, a dosage of 0.3 mg/kg ICG was injected central-venously. Transpulmonary ICG concentration curves were analyzed automatically using a computer system (COLD-Z021, Pulsion Medical Systems, Munich, Germany). By using the first ICG measurement in each patient after admission to the ICU, we analyzed 209 pairs of ICG disappearance rate and ICG blood clearance. Linear regression analysis revealed a correlation of r² = 0.77 between ICG-PDR and ICG blood clearance.Conclusion ICG-PDR does reflect ICG blood clearance with sufficient accuracy in critically ill patients and may be used as a surrogate.     

Incidence and outcome of metabolic disarrangements consistent with citrate accumulation in critically ill patients undergoing continuous venovenous hemodialysis with regional citrate anticoagulation

Background

Systemic citrate accumulation is a complication of regional citrate anticoagulation (RCA) during continuous renal replacement therapy (CRRT). Our objective was to determine the incidence of clinical signs consistent with citrate accumulation in a large and representative cohort of intensive care unit patients undergoing RCA-CRRT.

Methods

Patients treated with RCA-CRRT during 2008-2010 were retrospectively analyzed. Decreased systemic ionized calcium (iCa), increased demand for calcium substitution, elevated total calcium to iCa ratio, and metabolic acidosis were evaluated as indicators for citrate accumulation.

Results

In the 3-year period, 1070 patients were treated with RCA–continuous venovenous hemodialysis. Metabolic signs of citrate accumulation occurred in 32 patients (2.99%, 64.5±14.0 years, 65.6% male, Acute Physiology and Chronic Health Evaluation score 34.2±9.7): systemic iCa decreased to 1.01±0.10 mmol/L with a simultaneous increase of the calcium substitution rate to 129%±26%, and the mean total calcium to iCa ratio increased to 2.51±0.54. All 32 patients had therapy-resistant shock with severe lactic acidosis (pH 7.20±0.11, lactate 136±61 mg/dL), indicating severe intracellular hypoxia. None of the patients survived.

Conclusions

The incidence of disarrangements consistent with citrate accumulation in patients undergoing RCA–continuous venovenous hemodialysis was low, taking place exclusively in patients with severe lactic acidosis due to multiorgan failure. This suggests that the appearance of citrate accumulation is secondary to a severe failure of cellular respiration.     

连续白蛋白循环吸附系统用于危重症合并肝衰竭患者治疗的探索

目的 探讨连续白蛋白循环吸附系统(continuous albumin circulating absorbent system,CACAS)用于危重症合并肝衰竭患者治疗的疗效及安全性.方法 30例危重症合并肝衰竭患者行CACAS治疗,监测治疗前后及治疗结束后12h患者生命征、肝功能、凝血功能变化,并经行统计学分析.结果 治疗结束后患者血胆红素水平较治疗前明显下降(治疗前后血总胆红素485.46±34.85 μmol/L比305.89±43.54 μmol/L P＜0.01,结合胆红素293.62±25.67 μmol/L比190.85±32.13 μmol/LP＜0.01,游离胆红素212.98±16.18 μmol/L比159.70±23.57 μmol/L P＜0.01),凝血酶原活动度明显上升(治疗前后凝血酶原活动度42％±8％比80％±3％ P＜0.01),患者神志均转清,其他指标治疗前后无显著变化,治疗结束后12h患者所有指标较治疗结束时无明显改变.结论 CACAS系统用于危重症合并肝衰竭患者的治疗有良好的疗效及安全性,是危重症肝衰竭患者进行人工肝治疗的一个良好的选择.     

Pharmacokinetics of piperacillin and tazobactam in critically ill patients with renal failure, treated with continuous veno-venous hemofiltration (CVVH)

Objective: Kinetics of piperacillin (pip), in combination with the beta-lactamase inhibitor tazobactam (taz) have been studied in volunteers and patients in relatively stable conditions. The fixed drug preparation appeared to have ideal pharmacokinetic properties if renal function was normal or slightly impaired, but no data are available for critically ill patients in anuric renal failure. This study should provide such data. Patients, design: We studied the pharmacokinetics in nine patients with multiple organ failure, including anuric renal failure, treated with continuous veno-venous hemofiltration (CVVH). Patients received a standard schedule of 4 g pip and 0.5 g taz administered over 0.5 h intravenously, 8 hourly. During 2 consecutive days, the serum levels of both compounds were determined, and total clearance (CI_T) was calculated from serum concentrations. Results: All nine patients completed day 1, and 8 completed day 2 of the protocol. On day 1, single-dose kinetics showed considerable spread, but pip/taz serum levels followed the pattern as expected, with a pip / taz concentration ratio of 20 : 1. On day 2, however, taz serum concentrations showed a relative increase as compared to pip, resulting in a change in the serum pip/taz concentration ratio to 10 : 1 on day 2. The CI_T of pip was 2.52 ± 1.38 l/h (t ¹/₂ : 5.9 ± 2.9 h), and CI_T of taz 4.44 ± 2.28 l/h (t ¹/₂ : 8.1 ± 3.7 h). The CI_T and t ¹/₂ of pip and taz correlated highly significantly with clearance by CVVH. Despite a higher CI_T, taz has a longer half-life, because of a higher volume of distribution. Conclusion: In CVVH dependent patients, pip/taz fixed drug preparations can be used initially, but the pip dosage should be increased relative to that of taz (or interval-adjusted) to prevent cumulation of taz, as compared to the active antimicrobial agent pip. Received: 19 February 1997 Accepted: 20 May 1997     

强化胰岛素治疗危重病患者40例

目的观察强化胰岛素治疗在危重病患者中的临床疗效。方法80例危重病患者随机分为两组,治疗组（40例）给予强化胰岛素治疗,使血糖维持在4．4—6．1mmol／L;对照组（40例）给予常规胰岛素治疗,使血糖控制在10．0—11．1mmol／L。观察两组患者使用抗生素的天数、使用呼吸机的天数、血透发生率、院内感染发生率及病死率。结果治疗组中使用抗生素天数（15±5）d,使用呼吸机天数（6±4）d,需行血透6例（15．0％）,院内感染6例（15．0％）,病死率17．5％,均明显低于对照组,P〈0．05,差异有统计学意义。结论对于危重病患者,当出现应激性高血糖时,强化胰岛素治疗可改善危重病患者的预后,降低其病死率。     

Reproducibility of thermodilution cardiac output determination in critically ill patients: Comparison between bolus and continuous method

Objective. A semi-continuous thermodilution method (CCO) was recently developed to measure cardiac output with less risk of bacterial contamination, fluid overload, and user-induced errors than the classical bolus technique (BCO). Previous comparison between these two methods showed negligible bias. However, large limits of agreement suggest that the two methods are not interchangeable. We hypothesized that this poor agreement may be due to differences in reproducibility.Methods. In 23 critically ill patients, 369 paired measurements of CCO and BCO were compared (range of cardiac outputs: 2.8 to 16 L/min). The reproducibility of BCO and CCO methods was evaluated on a sample of 205 and 209 determinations, respectively.Results. The comparison between the CCO and the BCO methods confirmed previous results: i.e., small bias (–0.39 L/min) and large limits of agreement -2.06 to +1.28 L/min). Reproducibility showed no bias for either the CCO or the BCO method. Limits of reproducibility agreement between repeated determinations were approximately 50% less for CCO than for BCO method: respectively –0.87 to +0.82 L/min for the CCO method and –1.56 to +1.37 L/min for the BCO method. Consequently, the threshold necessary to ascertain that the difference between two measurements was not due to the internal variability of the method (3 x SEM) was 0.39 for the CCO method and 0.75 L/min for the BCO method.Conclusion. Differences in reproducibility may explain the poor agreement between the CCO and BCO methods. The better reproducibility of the CCO method allows the detection of smaller variations in cardiac output and suggests the superiority of this new method.