Possible strategies to prolong circuit life during hemofiltration: three controlled studies

BACKGROUND AND AIMS: The prevention of filter clotting is an important goal in the management of continuous renal replacement therapy (CRRT). Anticoagulation is the mainstay of such prevention. However, other strategies might prolong filter life without increasing the risk of bleeding. We tested the effectiveness of three strategies (use of flat plate configuration, heparin administration into the air chamber and use of a larger membrane surface) aimed at prolonging circuit life without increasing the dose of anticoagulation. METHODS: Thirty-one critically ill patients with acute renal failure (ARF) managed with continuous venovenous hemofiltration (CVVH) were studied. Filters were randomized in a crossover design to three consecutive studies: (1) filtration with either hollow-fiber or flat-plate hemofilters, (2) administration of heparin dose pre-filter or divided into pre-filter and directly into the bubble trap chamber and (3) use of two different surface areas with Filtral 8 (surface area 0.75 m2) vs. Filtral 12 (surface area 1.30 m2) hemofilters. Results: Mean circuit life for flat-plate and hollow-fiber hemofilters (cohort 1) was 14.7 +/- 4.7 h and 17.1 +/- 2.8h respectively (NS). Mean circuit life for single heparin administration site vs. double site administration (cohort 2) was 17 +/- 3.2 h and 18 +/- 3.1 h respectively (NS). Mean circuit lifespan for 0.75 m2 and 1.30 m2 hemofilters was 16 +/- 12.2 h and 15.7 +/- 14.3 h respectively (NS) (cohort 3). Visible clot formation in the bubble trap chamber was a frequent cause of circuit failure. CONCLUSION: Neither flat plate membrane configuration nor increasing membrane surface area, nor heparin administration in the air chamber prolong circuit life during CWH. The bubble trap chamber is a frequent site of circuit clotting.     

Regional anticoagulation and antiaggregation for CVVH in critically ill patients: a prospective, randomized, controlled pilot study

Background: The aim of this study is to assess the efficacy and clinical safety of regional anticoagulation (heparin pre-filter plus post-filter protamine) plus antiaggregation (pre-filter prostacyclin) [Group 1 (G1)] vs. only systemic heparin anticoagulation without antiaggregation [Group 2 (G2)] in critically ill patients with acute renal failure undergoing continuous veno-venous haemofiltration (CVVH).
Methods: One hundred and ten patients were randomized in a prospective, controlled pilot study. G1 patients received 1000 U/h pre-filter heparin, 10 mg/h post-filter protamine sulphate and 4 ng/kg/min pre-filter prostacyclin, while G2 patients received 1000 U/h pre-filter heparin. The haemofilter transmembrane pressure (TMP) and lifespan, as well as the platelet count were observed 1 h before, and at 6, 12, 18, 24 and 36 h from the beginning of CVVH.
Results: Haemofilter TMP remained unchanged in G1 while it increased up to three times in G2 ( P =0.0002). The median filter lifespan was 68 h in G1 and 19 h in G2. The rate of spontaneous circuit failure was 24% in G1 and 93% in G2 ( P =0.0001). The platelet count was stable over the treatment period in G1 while in G2 it decreased progressively ( P =0.0073).
Conclusion: In critically ill patients suffering from acute renal failure, regional anticoagulation with pre-filter heparin and post-filter protamine plus antiaggregation during CVVH is a simple and safe procedure that prevents increases in filter TMP and increases circuit life time compared with systemic anticoagulation with pre-filter heparin only.     

枸橼酸-葡萄糖抗凝溶液在高危出血患者连续性血液净化中的应用

目的 研究商品化枸橼酸-葡萄糖抗凝溶液A(ACD-A液)应用于急性肾衰竭伴出血倾向高危患者连续性血液净化(CBP)抗凝的疗效及安全性。方法 12例伴出血或出血倾向患者行连续性静脉-静脉血液滤过(CVVH)，分为局部枸橼酸抗凝(RCA)组和对照组。RCA组共38例次，应用ACD-A液为抗凝剂自滤器前输入；于血路管的静脉侧补充10%葡萄糖酸钙。ACD-A液及钙剂输入速度根据血清及滤器后离子钙(iCa2+)水平调整以维持滤器后iCa2+ 0.30~0.40 mmol /L ，血清iCa2+ 0.9~1.2 mmol/L。对照组应用小剂量低分子肝素钠(1700~2500 IU，每12~24 h 1次)或不使用抗凝剂。比较两组血滤器使用时间；监测RCA组治疗前后血浆凝血酶原时间(PT)和部分凝血活酶时间(APTT)、酸碱变化及血清iCa2+、钠离子(Na+)水平。 结果 RCA组和对照组CBP总治疗时间分别为1192.5 h、596 h，各使用血滤器62个、42个。24 h和48 h血滤器的可使用率分别为:RCA组65.3%和24.5%；对照组14.5%和0。达使用终点的血滤器平均寿命，RCA组显著长于对照组[(29.4±21.0)(1.5~71.5)h比(14.2±8.2)(4.5~40)h，P < 0.01]。ACD-A抗凝治疗中，血PT、APTT、pH、碱剩余、iCa2+ 、Na+水平较治疗前基本保持不变；无1例次出血加重或新发出血、无1例次诱发肢体抽搐。结论 ACD-A液抗凝剂在有效监测的情况下，应用于伴出血倾向患者的CBP，是一种简便易行、安全有效的方法，有一定的临床应用及推广价值。     

Continuous venovenous hemofiltration: an alternative to continuous arteriovenous hemofiltration and hemodiafiltration in acute renal failure

Continuous venovenous hemofiltration (CVVH) has been used as an alternative to continuous arteriovenous hemofiltration (CAVH) and hemodiafiltration (CAVHD) in the management of critically ill patients with acute renal failure. This report describes our experience with the first 25 patients treated with CVVH at our institution. Vascular access was obtained through a single dual-lumen venous catheter. A blood pump was used to provide ultrafiltration pressure. An ultrafiltrate pump was incorporated to ensure predictable ultrafiltrate production rates. Safety features in the extracorporeal circuit included a venous drip chamber with bubble detector and an in-line pressure monitor. CVVH was initiated by a nephrologist and dialysis nurse and was maintained by the intensive care unit (ICU) nursing staff. Fifteen females and 10 males received CVVH therapy for a total of 193.5 days (average, 7.7 +/- 10.3 days; range, 0.5 to 48 days). Four of the 25 patients (16%) survived and were discharged from the hospital. Four additional patients (16%) survived the acute phase of their illness, but died from complications of their primary disease before discharge from the hospital. The mean weight change during CVVH was -7.9 +/- 7.0 kg (range, -26.5 to +2.9 kg). Metabolic waste products and electrolytes were adequately controlled by CVVH in all but one hypercatabolic patient. The mean heparin dose required was 6.5 +/- 4.2 U/kg/h and was adjusted to prevent filter clotting rather than to achieve a predetermined activated partial thromboplastin time (PTT). The median PTT was 35.8 seconds (range, 22.0 to 100; control, 19.5 to 29.5 seconds). Four episodes of volume-responsive hypotension occurred during the 193.5 treatment days. Only one patient experienced a hemorrhagic complication during CVVH. No patient experienced a complication related to vascular access. Twelve of 111 total hemofilters were changed because of clot formation. CVVH was well tolerated by patients and managed efficiently by the ICU nursing staff.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biocompatibility of Heparin-Coated Membrane Oxygenator During Cardiopulmonary Bypass

Abstract: The biocompatibility of the cardiopulmonary bypass (CPB) circuit, in which an oxygenator is solely heparinized, was assessed by systemic inflammatory reactions as an indicator during CPB. Fourteen patients, 11 males and 3 females, underwent coronary artery bypass surgery and were randomly divided into 2 groups of 7 patients each. For the heparin–coated oxygenator group (Group H), a heparin–coated membrane oxygenator was used in the CPB circuit, and in the control (Group C) an uncoated membrane oxygenator was employed. Systemic inflammatory reactions, such as platelet activation, prostaglandin production, complement activation, and activated granulocyte released substance, were measured prior to, during, and 6 h after CPB. The number of platelets decreased after protamine administration in both groups (14. 5 ±4. 7 times 10⁴/μl in Group H and 13. 8 ± 8. 7 times 10⁴/μd in Group C) and returned to baseline levels in Group H while it remained decreased in Group C at 6 h after CPB. The platelet factor 4 level was significantly lower in Group H (181 ± 40 ng/ml) than in Group C (297 ±131 ng/ml) after protamine administration. Thromboxane–B₂ (TXB₂) rose during CPB in both groups; however, there were significantly different levels of TXB₂ between the 2 groups at 60 min after CPB (293±258 pg/ml in Group H versus 408 ± 120 pg/ml in Group C) and after protamine administration (259 ± 122 pg/ml in Group H versus 709 ± 418 pg/ml in Group C). Plasma concentrations of granulocyte elastase were significantly lower in Group H at 30, 60 and 90 min, immediately after, and post–CPB than those of Group C. Although the oxygenator was solely heparinized in the CPB circuit, it was sufficiently effective to reduce inflammatory reactions during coronary artery bypass operation, and the heparin–coated surface seems to be more endothelium–like.     

Commercial low-citrate anticoagulation haemofiltration in high risk patients with frequent filter clotting

This study assessed the safety and efficacy of a commercial low-citrate concentration-based pre-filter replacement fluid during continuous veno-venous haemofiltration (CVVH) in patients with frequent filter clotting and high risk of bleeding. We used a commercial low-citrate fluid as pre-dilution replacement fluid during CVVH (citrate: 11 mmol/l (33 meq/l), sodium: 140 mmol/l, chloride: 108 mmol/l and potassium: 1 mmol/l). A calcium and magnesium infusion was delivered separately by central line for the maintenance of serum ionized calcium (Cai) and total magnesium (Mg). In this prospective observational study, 30 patients, 124 filters and 1,515 treatment-hours were observed. Median filter life of citrate CVVH was 9.5 hours. Filter life in the 48 hours prior to citrate CVVH was also observed. In the patients on prior non-anticoagulant CVVH (n=14) filter life increased significantly with citrate (9.5 hours vs 5 hours; P<0.0001). In patients on prior heparin CVVH (n = 15), filter life was similar with citrate (10 hours vs 8 hours; P = 0.68). However, in patients with prior early/frequent filter clotting despite heparin (n = 11) filter life increased significantly (10 hours vs 7 hours; P=0.038). Of 411 serum Cai measurements, none showed a Cai < 0.85 mmol/l and, of 84 observations, none showed a serum Mg<0. 6 mmol/l. One patient with sepsis and shock needed to cease citrate CVVH because of progressive ionized hypocalcaemia and increasing anion gap. No other adverse effects were observed. In selected patients, CVVH with a commercial low-citrate concentration solution as pre-filter replacement fluid and a simultaneous calcium and magnesium infusion protocol appears generally safe. Filter life was acceptable and superior to that achieved with previous treatment.     

Evaluation of biodistribution by local versus systemic administration of 99mTc-labeled pamidronate

Background There is an emerging interest in utilizing local and systemic administration of bisphosphonates in orthopedics. The primary objective of this study was to use ^99mTc-pamidronate (^99mTc-PAM) as a tool and compare bone and tissue uptake by local versus systemic administration. Methods ^99mTc-PAM was administered intravenously (i.v.), subcutaneously (s.c.) and by direct application (d.a.) on a surgically exposed and fractured femur (d.a.#f). The animals were imaged at 2 h and 24 h after administration and then killed. Organs were harvested, and their radioactivity was estimated. Specific uptake in the right femur was compared between groups, as was systemic exposure to ^99mTc PAM. Results Bone uptake of ^99mTc-PAM in the i.v. and s.c. groups was 2.2 ± 0.15 and 0.65 ± 0.07% ID/g, respectively, at the 2 h time point. Uptake by surgically exposed right femur (d.a) was 5.15 ± 0.26% ID/g, 134% higher than the femoral uptake by the i.v. method (P < 0.05). In the presence of exposed bone when the femur was fractured (d.a.#f), the uptake was 7.89 ± 0.46% ID/g, a further 50% increase (P < 0.05). The uptake of ^99mTc-PAM increased after 24 h of application to 2.4 ± 0.15, 1.53 ± 0.09, 7.94 ± 0.99, and 13.2 ± 0.80% ID/g) for i.v., s.c., d.a., and d.a.#f methods, respectively. The increases in uptake for the d.a. methods were significantly higher than for the local methods at the 24-h time point (P < 0.05). Although renal uptake was comparable with the i.v. and s.c. methods (0.22 ± 0.03 and 0.22 ± 0.04% ID/g), it was significantly lower with the d.a. methods (0.05 ± 0.07 and 0.16 ± 0.07% ID/g) (P < 0.05). The corresponding urinary excretion was 55%, 45%, 36%, and 35% of the injected dose at 24 h. Conclusions The results indicate that the bone uptake of ^99mTc-PAM was significantly higher (P = 0.001) and the kidney uptake significantly lower (P = 0.004) with the d.a. methods than with the i.v. or s.c. method. The findings indicate the need for further study into the potential of local administration of bisphosphonates in the presence of orthopedic indications.     

The beneficial effects of aminophylline administration on heparin reversal with protamine

The aim of this study was to demonstrate the beneficial effects of aminophylline on protamine cardiotoxicity. Thirty-four patients were examined, 17 of whom received aminophylline 3 mg/kg before protamine administration, being the study group, while the other 17, being the control group, did not. All cardiac output and biochemical measurements were evaluated 5 min following protamine administration. The cAMP level was 43.4±3.51 pmol/ml in the study group and 18.7±2.98 in the control group (P<0.0001) before protamine administration, while the oxygen extraction rate decreased from 49% to 44±2% in the control group, and from 51.2% to 47±3% in the study group (P<0.03). The N-acetyl glucosaminidase value was 16.9±13.9 pmol/ml in the study group and 27.8±1.47 pmol/ml in the control group (P<0.01), and myocardial lactate extraction was −0.20±0.03 in the control group and −0.07±0.07 in the study group (P<0.001). The left ventricular stroke work index was 28.6±3.14 gm/m² in the control group and 37±6.77 gm/m² in the study group (P <0.002). The findings of this study led us to conclude that the adverse effects of heparin neutralization using protamine can be relieved by aminophylline.     

Comparison Between D901 Lilliput 1 and Kids D100 Neonatal Oxygenators: Toward Bypass Circuit Miniaturization

Progress in biomaterial technology and improvements in surgical and perfusion strategy ameliorated morbidity and mortality in pediatric cardiac surgery. In this study, we describe our clinical experience comparing performance of two neonatal oxygenators. From January 2002 to March 2011, 159 infants with less than 5 kg body weight underwent heart surgery. Ninety‐four patients received a D901 Lilliput 1 oxygenator with standard bypass circuit (group A), while 65 received a D100 Kids with miniaturized bypass circuit (group B). Miniaturization consisted in shortened arterial, venous, cardioplegia, and pump‐master lines. Priming composition consisted in Ringer's acetate solution with addition of albumin and blood, with target hematocrit of 24% or greater. In group B cardiopulmonary bypass (CPB) was vacuum‐assisted and started with an empty venous line. Modified ultrafiltration and Cell‐Saver blood infusion was routinely applied in both groups. Average ± standard deviation (SD) age at repair was 37 ± 38 days in group A and 59 ± 60 days in group B (P = 0.005). Average ± SD weight, height, and body surface area were 3.5 ± 0.7 kg, 52 ± 4 cm, and 0.22 ± 0.03 m², respectively, in group A, and 3.7 ± 1 kg, 53 ± 5 cm, and 0.23 ± 0.02 m², respectively, in group B (P = not significant [NS]). Male sex was predominant (55 vs. 58%, P = NS). Priming volume was 524 ± 67 mL (group A) and 337 ± 53 mL (group B) (P = 0.001). There were no statistical differences in hemoglobin at the start, during, and at the end of CPB, but group A required higher blood volume added to the prime (111 ± 33 vs. 93 ± 31 mL, P = 0.001). In group B, two surgical procedures were completed in total hemodilution. In group B, CPB time and aortic cross‐clamp time were shorter than in group A (106 ± 52 vs. 142 ± 78 min and 44 ± 31 vs. 64 ± 31 min, respectively, P = 0.001). There were 16 hospital deaths in group A and 4 in group B (P = 0.04). Durations of mechanical ventilation and intensive care unit stay were 5.3 ± 3.2 vs. 4.1 ± 3.2 days (P = 0.02) and 6.5 ± 4.9 vs. 5.1 ± 3 days (P = 0.03), respectively. There were significant differences in inotropic score (1083 ± 1175 vs. 682 ± 938, P = 0.04) and blood postoperative transfusion (153 ± 226 vs. 90 ± 61 mL, P = 0.04). Twenty‐seven patients in group A and 10 in group B presented with major adverse postoperative complications (P = 0.04). Use of neonatal oxygenators with low priming volume, associated with a miniaturized bypass circuit, seems to be a favorable strategy to decrease postoperative morbidity after cardiac surgery in neonates and infants.     

Citrate anticoagulation in pediatric continuous venovenous hemofiltration

Regional citrate anticoagulation has become a common alternative to systemic heparinization in adult continuous venovenous hemofiltration (CVVH) practice. We report our experience with the technique in critically ill children. We carried out a retrospective chart review of a 22-bed pediatric intensive care unit. CVVH with pre-filter citrate and systemic calcium replacement infusions was performed according to a strict protocol in nine consecutive critically ill children. All charts were reviewed for patient characteristics and CVVH circuit parameters, including filter survival. All complications were noted. Nurse specialists were interviewed about the practical management of citrate anticoagulation. All patient measurements of blood urea nitrogen, creatinine, sodium, ionized calcium (iCa), potassium, and bicarbonate were collected over the CVVH period. In seven patients, 12 simultaneous citrate measurements were taken from patient blood, pre-filter blood, and hemofiltrate fluid. Nine patients (mean age 8.8±6.8 years) were treated with CVVH and regional citrate anticoagulation for 1–14 days (mean 5.2±4.0 days). Of 19 filters used, 15 were replaced non-electively (mean filter survival 55.6±22.0 h). Control of azotemia and hyperkalemia was good. Sodium and iCa levels were well maintained. Bicarbonate levels were elevated in four patients without adverse effects. The mean systemic citrate level at equilibrium was 1.6±0.23 mmol/l. No systemic bleeding complications were observed. In children, regional citrate anticoagulation provides equivalent filter survival to heparin without bleeding complications. With good staff preparation, it is simple to perform and safe with respect to metabolic side effects.     

Acute Sodium Chlorite Poisoning Associated with Renal Failure

Background and Objectives: Different techniques of continuous renal replacement therapy (CRRT) might have different effects on azotemic control. Accordingly, we tested whether continuous veno-venous hemodiafiltration (CVVHDF) or continuous veno-venous hemofiltration (CVVH) would achieve better control of serum creatinine and plasma urea levels. Design: Retrospective controlled study. Setting: Two tertiary Intensive Care Units. Patients: Critically ill patients with acute renal failure (ARF) treated with CVVHDF (n = 49) or CVVH (n = 50). Interventions: Retrieval of daily morning urea and creatinine values before and after the initiation of CRRT for up to 2 weeks of treatment. Measurements and Results: Before treatment, serum urea and creatinine concentrations were significantly lower in the CVVH group than in CVVHDF group (urea: 31.0 ± 15.0 mmol/L for CVVHDF and 24.7 ± 16.1 mmol/L for CVVH, p = 0.01, creatinine: 547 ± 308 µmol/L vs. 326 ± 250 µmol/L, p < 0.0001). These differences were still significant after 48 h of treatment (urea: 20.1 ± 8.3 mmol/L vs. 14.1 ± 6.1 mmol/L; p = 0.0003, creatinine: 360 ± 189 µmol/L vs. 215 ± 118 µmol/L; p < 0.0001). Throughout the duration of therapy, mean urea levels (22.3 ± 9.0 mmol/L for CVVHDF vs. 16.7 ± 7.8 mmol/L for CVVH, p < 0.0001) and mean creatinine levels (302 ± 167 vs. 211 ± 103 µmol/L, p < 0.0001) were better controlled in the CVVH group. Conclusions: CRRT strategies based on different techniques might have a significantly different impact on azotemic control.     

Hemodynamic Maladjustment and Disease Progression in Nephrosis with FSGS

Idiopathic nephrotic syndrome (NS) associated with focal segmental glomerulosclerosis (FSGS) and severe renal function impairment is usually refractory to the conventional treatment and progresses to end‐stage renal disease. Herein, we reported 10 patients with NS‐FSGS who had initially had CCr 34 ± 12 mL/min/1.73m² (normal 120 mL/min/1.73m²), FE Mg 7.8 ± 2.6% (normal 2.2%), 24‐h urinary protein 3.1 g (normal < 200 mg) and been followed up for over 10 years. The initial intrarenal hemodynamic study revealed a marked elevation of efferent arteriolar resistance (RE 17289 ± 8636 dyne.s.cm^{? 5}; normal 3000 dyne.s.cm^{? 5}), intraglomerular hypertension (PG 57 ± 1 mm Hg; normal 52 mm Hg), hyperfiltration (FF 0.24; normal 0.2), marked reductions in GFR 35 ± 17 mL/min/1.73m², renal plasma flow (RPF 159 ± 61 mL/min/1.73m²; normal 600 mL/min/1.73m²) and peritubular capillary flow (PTCF 123 ± 57 mL/min/1.73m²; normal 480 mL/min/1.73m²). Such a hemodynamic alteration indicated a hemodynamic maladjustment with a preferential constriction at RE. Treatment consists of multidrugs, namely angiotensin converting enzyme inhibitor, calcium channel blocker, antiplatelet and anticoagulant, with or without angiotensin II receptor antagonist. Following the treatment, correction of hemodynamic maladjustment has been achieved which is characterized by reductions in RE 6046 ± 2191 dyne.s.cm^{? 5}, PG 52 ± mm Hg, FF 0.19 ± 0.1 and increments in RPF 341 ± 118 mL/min/1.73m², PTCF 280 ± 106 mL/min/1.73m² and GFR 64 ± 17 mL/min/1.73m². Coinciding with hemodynamic improvement, there has been a steadily increased creatinine clearance and improvement in FE Mg 4.3 ± 2.6% and suppression of proteinuria 0.29 ± 0.4g/24 h after the period of follow‐up of greater than 10 years.     

Minimally Circulatory‐Assisted On‐Pump Beating Coronary Artery Bypass Grafting for Patients With Complex Conditions for Off‐Pump Surgery

Off‐pump coronary artery bypass grafting (OPCAB) in patients with acute myocardial infarction (AMI) is difficult because of circulatory deterioration during displacement of the heart. At our institution, we performed minimally circulatory‐assisted on‐pump beating coronary artery bypass grafting (MICAB) in these patients. During MICAB, support flow was controlled at a minimal level to maintain a systemic blood pressure of approximately 100 mm Hg and a pulmonary arterial systolic pressure of <30 mm Hg, providing optimal pulsatile circulation for end‐organ perfusion and prevention of heart congestion. From September 2006 to March 2012, MICAB was performed in 37 patients. Either emergent or urgent MICAB was performed in 27 patients following AMI because of hemodynamic instability during reconstruction. Elective MICAB was performed in the remaining 10 patients because of dilated left ventricle (LV) or small target coronary arteries. The details of bypass grafts, perioperative renal function, and early and mid‐term morbidity and mortality were compared between the patients who received MICAB and the 37 consecutive patients who underwent OPCAB during the study period at our hospital. The assist flow indices (actual support flow/body surface area) during anastomosis to the left anterior descending artery, left circumflex artery, and right coronary artery were 0.95 ± 0.48 L/min/m², 1.32 ± 0.53 L/min/m², and 1.15 ± 0.47 L/min/m², respectively, in the emergent and urgent patients following AMI, and 0.44 ± 0.39 L/min/m², 1.25 ± 0.39 L/min/m², and 1.14 ± 0.43 L/min/m², respectively, in the elective patients with either dilated LVs or small target vessels. The lowest mixed venous oxygen saturation during pump support in the MICAB group was significantly higher than that in the OPCAB group (83.8 ± 10.8%, 71.6 ± 7.5%, P < 0.001). Comparing MICAB and OPCAB, the median number of distal bypass grafts for both groups was 4 (25th, 75th percentile: 3, 4) (P = 0.558); the complete revascularization rates were 94.6 and 97.3%, respectively (not significant [NS]); the acute patency rates were 98.9 and 99.2%, respectively (NS); and the 30‐day mortality rates were 2.7 and 0%, respectively (NS). No instances of either cerebrovascular complications or newly occurring postoperative renal failure were noted in either group. There were no statistically significant differences between the groups with respect to early and mid‐term results (freedom from all‐cause death: 82.9 vs. 86.5%, respectively, and freedom from cardiac events at 3 years: 96.4 vs. 96.4%, respectively). MICAB is a safe alternative to OPCAB, particularly in patients with AMI and dilated LV. MICAB is associated with high rates of complete revascularization and acute graft patency, adequate preservation of end‐organ function, and early and mid‐term results comparable with those observed following OPCAB.     

A novel isotonic‐balanced electrolyte solution with 1% glucose for perioperative fluid management in children‐ an animal experimental preauthorization study

Background: The recommendations for perioperative maintenance fluid in children have been adapted from hypotonic to isotonic electrolyte solutions with lower glucose concentrations (1–2.5% instead of 5%) to avoid hyponatremia or hyperglycemia. Objective: The objective of this prospective animal study was to determine the margin of safety of a novel isotonic‐balanced electrolyte solution with 1% glucose (BS‐G1) in comparison with normal saline with 1% glucose (NS‐G1) in the case of accidental hyperhydration with a focus on acid–base electrolyte balance, glucose concentration, osmolality and intracranial pressure in piglets. Methods: Ten piglets (bodyweight 11.8 ± 1.8 kg) were randomly assigned to receive either 100 ml·kg^?1 of BS‐G1 or NS‐G1 within one hour. Before, during and after fluid administration, electrolytes, lactate, hemoglobin, hematocrit, glucose, osmolality and acid–base parameters were measured. Results: Unlike BS‐G1, administration of NS‐G1 produced mild hyperchloremic acidosis (base excess BS‐G1 vs NS‐G1, baseline 1.9 ± 1.7 vs 2.9 ± 0.9 mmol·l^?1, study end 0.2 ± 1.7 vs ?2.7 ± 0.5 mmol·l^?1, P < 0.05, chloride BS‐G1 vs NS‐G1 baseline 102.4 ± 3.4 vs 102.0 ± 0.7 mmol·l^?1, study end 103.4 ± 1.8 vs 109.0 ± 1.4 mmol·l^?1P < 0.05). The addition of 1% glucose led to moderate hyperglycemia (P < 0.05) with a concomitant increase in serum osmolality in both groups (P < 0.05). Conclusion: Both solutions showed a wide margin of safety in the case of accidental hyperhydration with less acid–base electrolyte changes when using BS‐G1. This novel solution could therefore enhance patient’s safety within the scope of perioperative volume management.     

Sertoli cell nuclear changes in human testicular biopsies as revealed by three dimensional reconstruction

Summary. Serial semithin sections of human testicular biopsy material were used for three-dimensional reconstruction in order to obtain information about Sertoli cell nuclei in normal and pathologically altered seminiferous epithelia. The three dimensional reconstruction program is based on the triangulation of image point series. It includes a calculation modus for determining surfaces and an approximation formula for the estimation of volumes. Nuclei from the following specimens were reconstructed and for each the volume (v), surface (s), and a quotient (v/s), which is regarded as a marker for the degree of membrane infoldings, were calculated as follows: (1) For normal spermatogenesis (stage 1, 2, 3, 5; n=18) v = 409.7 ± 33.0 μm³, s = 429.6±40.5 μm², v/s = 0.96 ± 0.05. The values revealed no stage-specific differences; (2) for hypospermatogenesis (n=9) v = 493.7 ± 33.7 μm³, s = 462.6 ± 51.4 μm², v/s = 1.07 ± 0.085; (3) for spermatogenic arrest at the level of primary spermatocytes (n = 4) v = 537.8 ± 49.5 μm³, s = 424.4 ± 28.7 μm², v/s = 1.27 ± 0.052; (4) for spermatogenic arrest at the level of spermatogonia (n = 17) v = 472.4 ± 110.3 μm³, s = 397.8 ± 64.2 μm², v/s = 1.18 ± 0.106; (5) for Sertoli-Cell Only Syndrome (n=14) v = 438.7 ± 42.6 μm³, s = 345.1 ± 38.0 μm², v/s = 1.28 ± 0.087; (6) for hypoplastic tubules in a biopsy showing mixed atrophy (n=19) v = 275.6 ± 53.2 μm³, s = 228.8 ± 26.0 μm², v/s=1.20±0.115; (7) for ovot-estis (46xx, 47xxy) (n=14) v = 417.3±71.2 μm³, s = 317.2±26.3 μm², v/s= 1.31±0.13 and (8) for carcinoma in situ (n=25) v = 436.3±83.1 μm³, s = 338.2±64.4 μm², v/s = 1.30±0.08. A significant increase of nuclear volume was found in Sertoli cells of all specimens showing different types of spermatogenic impairment (maturation arrest, hypospermatogenesis) and a significant decrease in Sertoli-cell nuclei from hypoplastic tubules. Compared to normal, v/s was significantly increased in all specimens showing pathological alterations suggesting that developmental and/or functional Sertoli cell defects seem to be constantly associated with spermatogenic impairment.     

Albumin dialysis without anticoagulation in high-risk patients: an observational study

Severe liver failure causes coagulopathy and high bleeding risk. Albumin dialysis with Molecular Adsorbent Recirculating System (MARS) (Gambro, Lund, Sweden) is useful for treatment. However, anticoagulation during its use is of uncertain value. We omitted heparin‐saline priming and intradialytic heparin and examined its effects. Albumin dialysis was performed in critically ill patients with intermittent circuit saline flushes (2664 ± 2420 mL per treatment). A total of 12 patients (M : F = 10:2; age 49 ± 9 years) were thus treated: 6 for fulminant hepatic failure and 6 for acute‐on‐chronic liver failure. The overall hospitalization duration was 31 ± 30 days. A total of 44 treatment sessions were performed (average 8 ± 7 sessions per patient). Prescribed versus achieved MARS duration were 13 ± 3 versus 11 ± 4 h, P < 0.05. Twenty‐three percent (10/44) of MARS sessions clotted, 11% (5/44) of treatments were electively terminated, and 2% (1/44) developed vascular catheter occlusion. Spontaneous bleeding occurred in 9% (4/44). Pre‐ versus post‐MARS systemic and blood circuit transmembrane pressures (mm Hg), and albumin dialysate afferent and efferent pressures were all stable. Coagulation indices were (pre‐ vs. post‐MARS): (i) prothrombin time (seconds): 36 ± 30 versus 42 ± 33, P = 0.143; (ii) activated partial thromboplastin time (seconds): 78 ± 43 versus 88 ± 45, P = 0.117; and (iii) platelet count (×10³/µL): 87 ± 40 versus 76 ± 48, P = 0.004. Systemic blood solute concentrations pre‐ versus post‐MARS were: (i) serum urea (mg/dL): 22.4 ± 19.6 versus 14.0 ± 8.4, P < 0.05; (ii) serum creatinine (mg/dL): 2.8 ± 2.3 versus 1.9 ± 1.5, P < 0.05; (iii) total bilirubin (mg/dL): 29.5 ± 8.8 versus 20.5 ± 5.1, P < 0.05; and (iv) plasma ammonia (µg/dL): 186 ± 85 versus 129 ± 66, P < 0.05. Anticoagulant‐free albumin dialysis remained effective despite frequent circuit clotting. This led to significant exacerbation of thrombocytopenia although bleeding risk remained low.     

Heparin–coated circuit during cardiopulmonary bypass

A prospective randomized study was performed to investigate the effect of surface coating with covalently endpoint–attached heparin (Carmeda Bio Active Surface) and reduced general heparinization on haematological indices and complement C5 activation. Care was taken to optimize the rheological design of the system using centrifugal pump and a closed system without venting or machine suction. Twenty patients scheduled for aortocoronary bypass grafting (EF > 0.5) participated in the study. Ten patients were randomized to be treated with heparin–coated equipment (CBAS) and reduced i.v. heparin (1.5 mg kg^-1) while 10 patients treated with identical but noncoated equipment and full heparinization (3 mg–kg^-1) served in a Control group. A vacuum suction was used to collect the blood from the operating field and it was autotransfused at weaning from extracorporeal circulation (ECC). Blood samples were obtained from the venous (precircuit) and arterial (postcircuit) side. We used a new and very specific method for detection of C5a based on monoclonal antibodies. The concentration of C5a was low in both groups during the operation but a significant increase was seen on days 1 and 2. In the Control group there was an increase from 10.2 ngml^-1±1.2 to 27.5 ng ml^-1 ± 4.8 on day 2 and in the CBAS group from 10.7 ng ml^-1 ± 1.2 to 35.6 ng ml^-1 ± 11.6 on day 2 (NS between groups). The granulocytes and total leukocyte count increased at the end of ECC and was maintained at the elevated level throughout the study period. The amount of free haemoglobin was high in the autotransfused blood in both groups. The present results confirm the feasibility of reducing general heparin when using heparin–coated systems but the study does not support the superiority of such coating with regard to biocompatibility in short procedures with a Theologically optimized circuit. The potential benefit from reduced heparin and protamine has not been fully evaluated.     

Urokinase can reduce heparin dose in patients with hypercoagulable states during hemodialysis

Abstract

Heparin is routinely administered at high doses during hemodialysis to patients with hypercoagulable states. This study aimed to evaluate the safety and efficacy of low-dose heparin in combination with urokinase in this patient population. The presence of a hypercoagulable state was confirmed by thromboelastography. Doses of heparin and urokinase were adjusted based on activated partial thromboplastin time (APTT). Clotting in the extracorporeal circuit was evaluated by a semi-quantitative index. Prothrombin time (PT) and APTT were measured before, during and after dialysis. Kt/V_urea was used to assess the efficacy of dialysis. D-dimer levels were measured 2?h after the start of hemodialysis. Hemodialysis data with heparin administered alone prior to dialysis were used as control in the present study. With urokinase treatment, the initial dose of heparin was reduced by 45.0?±?11.4% during hemodialysis and the maintenance dose by 46.8?±?12.8% compared with heparin alone. No side effects due to urokinase were observed. Bleeding events were rare. Post-dialysis PT (12.99?±?1.41 vs. 15.22?±?3.12?s, p?=?0.02) and APTT (97.75?±?43.62 vs. 140.16?±?30.12?s, p?=?0.002) with urokinase plus heparin were significantly shorter than with heparin alone. Finally, during dialysis, D-dimer levels were significantly higher with heparin alone (0.21?±?0.11?mg/L) than with heparin and urokinase (0.169?±?0.122?mg/L, p?=?0.017). In conclusion, urokinase significantly reduced the dose of heparin required during hemodialysis without any side effects in patients with hypercoagulable states during hemodialysis.     

Iloprost for Additional Anticoagulation in Continuous Renal Replacement Therapy—A Pilot Study

Purpose. The aim of this pilot study was to compare the effect of heparin anticoagulation with and without iloprost administration during continuous renal replacement therapy (CRRT) in critically ill patients. Material and methods. In a prospective, randomized, controlled pilot study at an intensive care unit at a university hospital, 20 patients requiring CRRT were investigated. Patients were allocated into two groups: group 1, the heparin group; and group 2, the heparin plus 1 ng/kg/min iloprost. In both groups, activated partial thromboplastin time (aPTT) was adjusted to 40–50 sec. Observation time was a maximum of 7 days. Results. Median filter run time was significantly prolonged by iloprost administration to a median of 14 h (13–26 h) compared to 10 h (4–12 h) in the heparin group (p = 0.004). A decrease in platelet count was attenuated by iloprost administration (p = 0.012). There were no bleeding complications in either group. Hemofiltration efficiency did not differ significantly between the groups. Conclusion. Additional administration of iloprost prolonged the filter run time of continuous veno-venous hemofiltration (CVVH) in this setting and attenuated the fall in platelet count during CRRT.     

Site-specific therapeutic angiogenesis after systemic administration of vascular endothelial growth factor

Purpose: Recent experimental studies have established the feasibility of therapeutic angiogenesis; in all cases, this has been achieved with local administration of angiogenic growth factors. This study was designed to investigate the hypothesis that systemic administration of an angiogenic growth factor specifically mitogenic for endothelial cells — vascular endothelial growth factor (VEGF) — could augment collateral vessel development in a rabbit ischemic hindlimb model.Methods: Ten days after the ligation of the external iliac artery and excision of the common and superficial femoral arteries in one limb of New Zealand white rabbits, heparin (800 IU, n = 13), VEGF (1 mg, n = 3; 5 mg, n = 5), heparin (800 IU) + VEGF (1 mg, n = 5; 5 mg, n = 7), or saline solution (n = 8) was injected as a single bolus in a marginal ear vein. Collateral vessel formation and limb perfusion were assessed 10 and 30 days after treatment.Results: Animals in both VEGF-treated groups had a significantly higher (p < 0.01) increase in calf blood pressure ratio at day 10 (control, 0.44 ± 0.02; heparin, 0.47 ± 0.02; VEGF, 0.60 ± 0.01; heparin + VEGF, 0.61 ± 0.02) and day 30 (control, 0.49 ± 0.05; heparin, 0.48 ± 0.02; VEGF, 0.70 ± 0.03; heparin + VEGF, 0.73 ± 0.03). Both VEGF-treated groups had a significantly higher (p < 0.05) angiographic score at day 30 (control, 0.28 ± 0.01; heparin, 0.28 ± 0.01; VEGF, 0.37 ± 0.01; heparin + VEGF, 0.38 ± 0.02). Maximum flow reserve at day 30 in the ischemic limb was higher (p < 0.05) in VEGF-treated rabbits (control, 1.87 ± 0.07; heparin, 1.92 ± 0.08; VEGF, 2.42 ± 0.16; heparin + VEGF, 2.33 ± 0.12). Capillary density was higher (p < 0.01) in the ischemic muscles of VEGF-treated rabbits (control, 156 ± 10/mm²; heparin, 178 ± 8/mm²; VEGF, 230 ± 10/mm²; heparin + VEGF, 233 ± 8/mm²).Conclusions: This series of in vivo experiments demonstrates that intravenous administration of VEGF, with or without heparin, results in both anatomic and physiologic evidence of enhanced collateral vessel formation in the rabbit ischemic hindlimb. Single-bolus systemic administration of VEGF may be a feasible therapeutic strategy in patients with lower-extremity ischemia. (J VASC SURG 1995;21:314-25.)