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.     

Cardiotomy suction versus red cell spinning during repair of descending thoracic aortic aneurysms

Two consecutive series of patients undergoing repair of descending thoracic and thoracoabdominal aortic aneurysms with partial cardiopulmonary bypass and low systemic heparinization (activated coagulation time: ACT greater than 180 sec) for proximal unloading and distal protection were analyzed. During the surgical procedures, thoracic shed blood was recovered either with a red cell spinning autotransfusion device (n=10) or two pump suckers and Duraflo II heparin surface coated cardiotomy reservoirs (n=10). There were 5/10 acute lesions and 1/10 ruptures for the autotransfusion group versus 5/10 acute lesions and 2/10 ruptures for the cardiotomy group (NS). Extension of aortic resection (range 1-8) was 3.6+/-1.2 for autotransfusion versus 3.5+/-1.4 for cardiotomy suction (NS). Mean number of reimplanted patches for intercostal and visceral reperfusion was 0.3+/-0.6 for autotransfusion versus 0.6+/-1.0 for cardiotomy (NS). Perfusion time was 41+/-17 min for autotransfusion versus 60+/-19 min for cardiotomy (p less than 0.05) and cross clamp time was 33+/-14 min for autotransfusion versus 43+/-17 min for cardiotomy (p less than 0.01). Total heparin dose was for 9500+/-2100 IU for autotransfusion versus 9800+/-1300 IU for cardiotomy (NS). The mean of the lowest ACTs measured during perfusion was 281+/-121 sec for autotransfusion versus 258+/-58 sec for cardiotomy (NS). The total protamine dose given was 7800+/-2100 IU for autotransfusion versus 9700+/-1900 IU for cardiotomy (p less than 0.05). The volume of washed red cells prepared was 3186+/-1318 ml for autotransfusion versus 0 for cardiotomy (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyaluronan based heparin free coated open and closed extracorporeal circuits for high risk coronary revascularization

This prospective randomized study compares the inflammatory response and fibrinolytic activation of fully coated/uncoated and open/closed extracorporeal circuits (ECC) in high risk patients. Over a 2-month period, 48 patients with EuroSCOREs 6 or greater undergoing coronary revascularization were prospectively randomized to one of the four perfusion protocols: Group 1: Closed and totally hyaluronan based heparin free coated (Vision HFO-GBS-HF, Gish Biomedical, Rancho Santa Margarita, CA) ECC with a soft-shell coated venous reservoir (SVR11S2-HFC, Gish Biomedical) and a hard-shell cardiotomy (CAPVRF44, Gish Biomedical) (n = 12); Group 2: Closed and totally uncoated identical ECC with soft-shell uncoated venous reservoir and a hard-shell cardiotomy (n = 12); Group 3: Open, totally hyaluronan based heparin free coated ECC (n = 12); and Group 4: Control-open, uncoated ECC (n = 12). Blood samples were collected at T1: Baseline; T2: 15 minutes after cardiopulmonary bypass (CPB) initiation; T3: before cessation of CPB; T4: 15 minutes after protamine reversal, and T5: in the intensive care unit. Serum IL-6 levels were significantly lower at T2 in all study groups, at T3 for coated groups, and T4 for closed+coated group (p < .05 versus control). Creatine kinase M-band (MB) levels in coronary sinus blood demonstrated well preserved myocardium after CPB in both coated groups versus Control (p < .05). Neutrophil CD11b/CD18 levels were significantly lower for all study groups versus control at T2, for both coated groups at T3 and only for closed + coated group at T4 (p < .05). Postoperative hemorrhage (mL) was 510 +/- 40 in closed + coated and 536 +/- 40 in open + coated groups (control: 784 +/- 48, p < .05). No significant differences in thrombin-antithrombin complex and free plasma hemoglobin were observed. Desorbed protein amount on ECC (mg/dL) was 1.7 +/- .01 in closed+coated, 2.01 +/- .01 in open+coated, and 3.3 +/- .015 in control groups (p < or = .05). Use of a closed and completely heparin free coated ECC may reduce neutrophil degradation, cytokine release characterized by improved clinical outcomes including reduced blood loss, reduced requirement for inotropes, and reduced atrial fibrillation.     

Cardiopulmonary bypass over 24 hours without systemic anticoagulation: new horizons?

Open chest cardiopulmonary bypass was evaluated in eight canine experiments (mean bodyweight 37 +/- 7 kg) over 24 hours using either heparin surface coated equipment without systemic anticoagulation or standard equipment with systemic heparinization (ACT greater than 400 s). Mean duration of perfusion achieved was 23 +/- 2 hours in the group perfused without systemic anticoagulation versus 21 +/- 6 hours in the group with: [table; see text] These results show, that prolonged open chest perfusion by the means of heparin surface coated equipment without systemic anticoagulation can be performed with reduced blood trauma and without transfusion of blood products for 12 hours.     

Perfusion with low systemic heparinization during resection of descending thoracic aortic aneurysms.

Two series of 20 consecutive patients with aneurysms of the descending thoracic aorta (TAA) and thoraco-abdominal aorta (TAAA) underwent multisegmental aortic repair using either simple normothermic crossclamping and rapid reanastomosis (historic) or partial cardiopulmonary bypass (CPB) with heparin coated perfusion equipment and low systemic heparinization (actual). Chronic lesions were present in 14/20 patients (70%) for simple versus 13/20 (65%) for CPB (NS). Acute lesions (symptomatic less than 24 h) were present in 6/20 patients (30%) for simple versus 7/20 (35%) for CPB (NS). Dissecting lesions were observed in 4/20 patients (20%) for simple versus 8/20 (40%) for CPB (NS). Aneurysmal lesions were found in 16/20 patients (80%) for simple versus 12/20 (60%) for CPB (NS). Mean number of aortic segments (n = 8) resected was 3.2 +/- 1.1 for simple versus 4.0 +/- 1.2 for CPB (P less than 0.01). Replacement of the transdiaphragmatic aorta was performed in 10/20 patients (50%) for simple and 13/20 patients (65%) for CPB (NS). A heparin loading dose of 5000 IU for simple versus 100 IU/kg bodyweight for CPB was used. In the latter group, the activated clotting time was kept above 180 s during a mean perfusion time of 46 +/- 28 min at a mean pump flow of 2.2 +/- 0.7 l/min. Thirty-day survival for all (transdiaphragmatic) was 12/20 (5/10) patients for simple versus 20/20 (13/13) for CPB (P less than 0.002, P less than 0.01). One-year survival (all) was 11/20 patients (55%) for simple versus 19/20 (95%) for CPB (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Intrapulmonary shunting during deliberate hypotension with nifedipine, diltiazem and labetalol in dogs

Pulmonary shunt (Qs/Qt) was calculated in 49 mongrel dogs weighing 18-20 kg during mechanical ventilation, before and during deliberate hypotension with either nifedipine (group N), diltiazem (group D), labetalol (group L), or ethyl alcohol and polyethylene glycol (group E). A 30 per cent decrease in mean arterial blood pressure occurred after two minutes of nifedipine infusion, two minutes after diltiazem, and three minutes after labetalol; these effects lasted two hours after nifedipine administration, 90 minutes after diltiazem and three hours after labetalol. There was an accompanying significant decrease in systemic and pulmonary vascular resistance. Qs/Qt and cardiac output increased significantly after nifedipine infusion. Shunt increased (mean +/- S.E.) from 9.7 +/- 0.8 to 18.25 +/- 1.05 per cent at two minutes (p less than 0.0005); 19.05 +/- 1.2 per cent at 30 minutes (p less than 0.005); 17.5 +/- 1.6 per cent at two hours (p less than 0.01); and 12 +/- 1.1 per cent at three hours (p less than 0.025). No increase in shunt occurred after the administration of diltiazem, labetalol or polyethylene glycol and ethyl alcohol. Arterial oxygen tension (PaO2) decreased significantly after nifedipine infusion from 146 +/- 11.5 to 105 +/- 3.5 mmHg two minutes after infusion; to 89.5 +/- 3 mmHg 30 minutes after; 115 +/- 4.75 mmHg two hours after; and 130 +/- 10.75 mmHg three hours later. PaO2 was not significantly different after diltiazem, labetalol, or polyethylene glycol and ethyl alcohol administration. With nifedipine cardiac output increased from 2.25 +/- 0.3 to 3.95 +/- 0.25 after two minutes (p less than 0.005) to 3.85 +/- 0.35 after 30 minutes (p less than 0.005), 3.7 +/- 3 after two hours (p less than 0.01) to 2.9 +/- 1.1 after three hours. No significant increase in cardiac output occurred in groups D or L. These results suggest that only nifedipine infusion significantly alters oxygenation in dogs and therefore its use warrants caution in the presence of a preexisting abnormal Qs/Qt.     

Protection of the immature heart. Temperature-dependent beneficial or detrimental effects of multidose crystalloid cardioplegia in the neonatal rabbit heart

There are conflicting reports of the detrimental or beneficial effects of hypothermic cardioplegia in the immature heart. We therefore investigated the temperature-dependence of myocardial protection and the ability of single-dose and multidose infusions of cardioplegic solution to protect the immature heart during hypothermic ischemia. Isolated, working hearts (n = 6 per group) from neonatal rabbits (aged 7 to 10 days) were perfused aerobically (37.0 degrees C) for 20 minutes before infusion (2 minutes) with either perfusion fluid (noncardioplegia control) or St. Thomas' Hospital cardioplegic solution and ischemic arrest (for 4, 6, and 18 hours) at various temperatures between 10.0 degrees and 30.0 degrees C. Hearts arrested with cardioplegic solution received either one preischemic infusion only (single-dose cardioplegia) or repeated infusions at intervals of 60 or 180 minutes (multidose cardioplegia). Ischemic arrest with single-dose cardioplegia for 4 hours at 10.0 degrees, 20.0 degrees, 22.5 degrees, 25.0 degrees, 27.5 degrees, and 30.0 degrees C resulted in 96.0% +/- 4.3%, 96.6 +/- 2.5%, 87.0% +/- 3.8%, 71.8% +/- 10.0% (p less than 0.05 versus 10.0 degrees C group), 35.1% +/- 10.3% (p less than 0.01 versus 10.0 degrees C group), and 3.0% +/- 1.9% (p less than 0.04 versus 10.0 degrees C group) recovery of preischemic cardiac output, respectively. With 6 hours of ischemia at 20.0 degrees C, single-dose cardioplegia significantly (p less than 0.01) increased the recovery of cardiac output from 20.9% +/- 13.1% (control) to 76.4% +/- 4.4%, whereas multidose cardioplegia (infusion every 60 minutes) further increased recovery to 97.8% +/- 3.8% (p less than 0.01 versus control and single-dose cardioplegia). In contrast, after 6 hours of ischemia at 10.0 degrees C, cardiac output recovered to 93.4% +/- 1.2% (control) and 92.3% +/- 3.1% (single-dose cardioplegia), whereas multidose cardioplegia reduced recovery to 76.9% +/- 2.2% (p less than 0.01 versus both groups). This effect was confirmed after 18 hours of ischemia at 10.0 degrees C; single-dose cardioplegia significantly increased the recovery of cardiac output from 24.5% +/- 10.9% (control) to 62.9% +/- 13.3% (p less than 0.05), whereas multidose cardioplegia reduced recovery to 0.8% +/- 0.4% (p less than 0.01 versus single-dose cardioplegia) and elevated coronary vascular resistance from 8.90 +/- 0.56 mm Hg.min/ml (control) to 47.83 +/- 9.85 mm Hg.min/ml (p less than 0.01). This effect was not reduced by lowering the infusion frequency (from every 60 to every 180 minutes).(ABSTRACT TRUNCATED AT 400 WORDS)     

Disadvantages of prostacyclin infusion during cardiopulmonary bypass: a double-blind study of 50 patients having coronary revascularization

Prostacyclin (PGI2) has been suggested for use in cardiopulmonary bypass (CPB) because of its positive effects on platelet number and function. Fifty patients who underwent coronary artery bypass grafting using a bubble oxygenator received heparin, 3 mg per kilogram of body weight, and then were randomly assigned to receive PGI2, 25 ng/kg/min, beginning 5 minutes before and until the end of CPB (26 patients) or a placebo (24 patients). Both groups were similar in sex, age, heparin dose, protamine dose, and CPB time. During CPB, mean arterial pressure fell significantly with PGI2 (76 +/- 2 mm Hg to 53 +/- 2 mm Hg; p less than 0.05) and necessitated pressor substances. Platelet counts fell significantly in both groups with the start of CPB, but after 60 minutes were similar in both groups (118 +/- 9 X 10(3) versus 130 +/- 8 X 10(3); not significant [NS]) and were unchanged 3 hours after CPB. Total chest tube output was 647 +/- 51 ml (placebo group) versus 576 +/- 34 ml (PGI2 group) (NS); 18 of the patients given PGI2 required 26 transfusions compared with 16 transfusions in 8 of the patients given a placebo (p less than 0.05). In PGI2 patients, arterial oxygen tension on 100% oxygen fell from 281 +/- 18 mm Hg before CPB to 223 +/- 17 mm Hg immediately after CPB (p less than 0.05). The placebo patients did not show a change in this variable.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biocompatibility of extracorporeal circulation. In vitro comparison of heparin-coated and uncoated oxygenator circuits

Oxygenator/tubing sets coated with endpoint-attached heparin were compared to uncoated sets in a dynamic model of extracorporeal circulation. Biocompatibility was assessed by evaluations of complement activation and platelet loss. The median concentration of C3 activation products increased gradually from 12 AU/ml at baseline to 65 AU/ml after 120 minutes in the uncoated sets and from 12 AU/ml to 19 AU/ml after 120 minutes in the coated sets (p less than 0.002). The median concentration of the terminal complement complex in the uncoated sets increased gradually from 3.1 AU/ml at baseline to 18.2 AU/ml after 120 minutes. In the coated sets the terminal complement complex reached a peak of 12.0 AU/ml at 15 minutes and returned to baseline values at 60 minutes. Median platelet loss at 120 minutes was 166 x 10(9) in the uncoated and 21 x 10(9) in the coated sets (p less than 0.01). Heparin coating thus improved biocompatibility by reducing both complement activation and platelet loss.     

Clinical performance and biocompatibility of novel hyaluronan-based heparin-bonded extracorporeal circuits

We tested documented in vitro and ex vivo advantages of novel hyaluronan based heparin bonded extracorporeal circuits in a prospective randomized study. During the period from June until September 2005, 40 patients undergoing reoperation for coronary artery bypass grafting were allocated into two equal groups (n = 20): Group 1 was treated with hyaluronan-based heparin-bonded circuits and group 2 was treated with uncoated control circuits. Complete blood count, fibrinogen, albumin, C3a, interleukin-2 levels, and thromboelastographic data were documented after induction of anesthesia (T1) and heparin administration before cardiopulmonary bypass (CPB) (T2), 15 minutes after initiation of CPB (T3), before cessation of CPB (T4), 15 minutes after reversal with protamine (T5), and the first postoperative day at 8:00 a.m. (T6). Hollow fibers were collected for consecutive biomaterial analysis by optical and scanning electron microscopy (SEM). Desorbed protein deposition on fibers was compared by spectrophotometry. Leukocyte counts were lower in T4-T6 in group 1 (p < .05). Platelet counts demonstrated significant differences at T4 and T5 in coated group (p < .05). Albumin and fibrinogen levels were better preserved in Group 1 at T4, T5 and T4, T6, consecutively (p < .05). C3a and IL-2 levels were lower at T3-T5 and T4-T5 in intervention group (p < .05). Postoperative hemorrhage was 412 +/- 50 mL in group 1 and 684 +/- 50 ml in group 2 (p < .05). Respiratory support time was shorter in group 1 versus control (p < .05). Platelet adhesion was significantly lower in intervention group. Amount of desorbed protein was 1.44 +/- 0.01 mg/dL in group 1 and 1.94 +/- 0.01 mg/dL in control (p < .05). SEM and spectrophotometry demonstrated better surface preservation in the hyaluronan coated group. Novel hyaluronan-based heparin-bonded circuits reduce platelet adhesion-aggregation and protein adsorption and provide better perioperative clinical parameters through platelet, albumin, and fibrinogen-sparing effects.     

Cardiopulmonary bypass without systemic heparinization. Performance of heparin-coated oxygenators in comparison with classic membrane and bubble oxygenators

Performance characteristics of heparin-coated hollow-fiber membrane oxygenators (COATED HFMO, n = 5) were evaluated in an open-chest dog model without systemic heparinization. Four other oxygenators were evaluated with standard systemic heparinization (300 IU/kg, activated clotting time more than 400 seconds): a standard hollow-fiber membrane oxygenator (HFMO, n = 5), an inversed hollow-fiber membrane oxygenator (IHFMO, n = 5), a plate membrane oxygenator (PLATE MO, n = 5) and a bubble oxygenator (BUBBLE O, n = 5). The 25 dogs (36 +/- 12 kg) were perfused after cavo-aortic cannulation for 6 hours with a mean flow of 100 ml/kg body weight. At the end of perfusion without systemic heparin, heparin-coated equipment was replaced in three animals with standard uncoated equipment for control studies. Besides continuous hemodynamic evaluation with Mikro-Tip pressure transducers (Millar Instruments, Inc., Houston, Texas), a standard battery of analyses was performed before, after mixing, and every 30 minutes during bypass. All animals could be perfused in accordance with the protocol. Blood-gas values (pH, arterial oxygen tension, and arterial carbon dioxide tension) were maintained within physiologic ranges for all groups. After 6 hours of perfusion, plasma hemoglobin levels were as follows: 0.57 +/- 0.51 gm/L for COATED HFMO without systemic heparinization versus 2.65 +/- 1.02 gm/L for HFMO (p less than 0.05), 1.77 +/- 0.48 gm/L for IHFMO (p less than 0.05), 1.96 +/- 0.41 gm/L for PLATE O (p less than 0.05), and 1.5 +/- 0.40 gm/L for BUBBLE O (p less than 0.05) with systemic heparinization. Platelet levels were highest for COATED HFMO with 47% +/- 36% without systemic heparinization versus 33% +/- 9% for HFMO, 12% +/- 2% for IHFMO, 36% +/- 17% for PLATE O, and 19% +/- 12% for BUBBLE O with systemic heparinization. Activated clotting time for COATED HFMO without systemic heparinization was 135 +/- 75 seconds before bypass, 207 +/- 21 seconds after mixing, and 131 +/- 20 seconds after 4 hours of perfusion. There was no statistically significant increase of plasma heparin levels in the group perfused without systemic heparin. Determination of fibrin split products during perfusion without systemic heparinization did not show a significant increase. At the end of perfusion all devices were disconnected and gently rinsed with saline: There were no macroscopic clots in the COATED HFMO group perfused without systemic heparin. However, uncoated equipment introduced for control in animals perfused without systemic heparin showed major clotting.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cardiac output-changes during hemodialysis with ultrafiltration

Cardiovascular hemodynamics were studied noninvasively before, during and after hemodialysis with ultrafiltration in 18 patients on chronic hemodialysis. The cardiac output (CO) was determined by a continuous wave Doppler method. Overall, no major CO changes were seen (7.8 +/- 0.6 l/min post- versus 7.4 +/- 0.5 l/min pre-dialysis). Mean blood pressure rose slightly but significantly from 103 +/- 4 mmHg before to 113 +/- 3 mmHg after hemodialysis (p less than 0.01). Important interindividual differences in the intradialytic evolution of CO were observed. In patients with previous myocardial infarction or dilated cardiomyopathy (n = 12), CO rose significantly from 7.3 +/- 0.7 l/min before to 8.4 +/- 0.6 l/min after hemodialysis (p less than 0.05), while in patients without manifest myocardial disease (n = 6) CO decreased from 7.5 +/- 0.7 l/min to 6.6 +/- 0.9 l/min (NS). Comparison of the evolution of CO in both groups by variance analysis revealed a significant difference (p less than 0.01). It is concluded that, in response to hemodialysis with ultrafiltration, CO probably will increase in patients with myocardial infarction or congestive cardiomyopathy, but probably will decrease in patients without.     

Noncardiogenic pulmonary edema after abdominal aortic aneurysm surgery.

Limb ischemia in experimental animals leads to white blood cell (WBC) and thromboxane (Tx)A2 dependent pulmonary dysfunction. This study examines the pulmonary sequelae of lower torso ischemia in 20 consecutive patients aged 63 +/- 5 years (mean +/- SEM) who underwent elective abdominal aortic aneurysm surgery. After 30 minutes of aortic cross-clamping, plasma TxB2 levels had risen from 77 +/- 26 pg/ml to 359 +/- 165 pg/ml (p less than 0.01) and was temporally related to increases in mean pulmonary artery pressure (MPAP) from 18 +/- 1 to 23 +/- 3 mmHg (p less than 0.01), as well as to increases in pulmonary vascular resistance (PVR) from 0.07 +/- 0.02 to 0.12 +/- 0.02 mmHg sec/ml (p less than 0.01). Each time that the aortic clamp was repositioned and with final declamping, after 83 +/- 10 minutes, there were further increases in MPAP to a peak of 32 +/- 2 mmHg (p less than 0.01) and in PVR to 0.26 +/- 0.030 mmHg sec/ml (p less than 0.01), corresponding to a plasma TxB2 level of 406 +/- 177 pg/ml (p less than 0.01). MPAP and PVR returned to baseline values within 30 minutes of declamping. Ten minutes after removal of the aortic clamp, platelet levels had fallen from 180 +/- 41 to 97 +/- 17 X 10(3)/mm3 (p less than 0.01) and WBC levels from 8900 +/- 1100 to 4700 +/- 400/mm3 (p less than 0.01). Both platelets and WBC returned towards normal levels, but at 24 hours, while WBC was elevated at 13000 +/- 900/mm3 (p less than 0.01), platelets were 44% of baseline at 135 +/- 14 X 10(3)/mm3 (p less than 0.01). Four to 8 hours after surgery, pulmonary dysfunction was manifest by increases in physiologic shunt from 9 +/- 2% to 16 +/- 2% (p less than 0.01), and peak inspiratory pressure (PIP) from 23 +/- 2 to 33 +/- 2 cmH2O (p less than 0.01). Chest radiography demonstrated interstitial pulmonary edema in all patients, whereas pulmonary artery wedge pressure was 12 +/- 2 mmHg, excluding the possibility of left ventricular failure. After 24 hours, pulmonary edema had resolved, and the PIP and PaO2 had both returned to baseline. These data indicate that reperfusion of the ischemic lower torso leads to the synthesis of TxA2, an event temporally related to pulmonary hypertension and transient leukopenia with subsequent pulmonary microvascular injury manifest by interstitial edema.     

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 ± 2.8 h 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 CVVH. The bubble trap chamber is a frequent site of circuit clotting.     

Beneficial effects of combination therapy with losartan and low-dose hydrochlorothiazide in the treatment of essential hypertension

Although strict blood pressure control is essential for the prevention of cardiovascular disease, there are many hypertensive patients whose current hypertension treatments are inadequate. Therefore, we designed a clinical study to evaluate the efficacy achieving a blood pressure reduction by combination therapy with losartan and a low-dose diuretic. In the 10 hypertensive patients treated with candesartan at 8 mg/day for more than 2 months, combination therapy with losartan at 50 mg/day and hydrochlorothiazide (HCTZ) at 12.5 mg/day was conducted for 3 months after the cessation of treatment with candesartan. Either immediately before the onset of combination therapy or 3 months after the treatment, the 24 hour ambulatory blood pressure(ABP) and pulse rate were measured every 30 minutes. Pulse wave velocity(PWV) and homeostasis model assessment insulin resistance index(HOMA-R) with fasting blood were also measured after 3 months. In the treatment with candesartan, the ABP was 134.4 +/- 8.7/88.1 +/- 6.1 mmHg at 24 hours, 139.7 +/- 8.4/91.3 +/- 7.1 mmHg in the daytime, 123.8 +/- 11.6/81.6 +/- 5.9 mmHg in the nighttime, and 139.3 +/- 10.3/92.3 +/- 7.3 mmHg in the early morning(6 : 00-8 : 00). After the switch to the combination therapy with losartan and HCTZ, the blood pressure changed to 126.8 +/- 9.3/81.6 +/- 7.0 mmHg (p < 0.05/p < 0.05) at 24 hours, 130.6 +/- 12.0/84.2 +/- 8.5 mmHg (p < 0.05/p < 0.05) in the daytime, 119.3 +/- 8.7/76.6 +/- 6.5 mmHg (NS/NS) in the nighttime, and 129.7 +/- 11.7/84.0 +/- 9.2 mmHg(p < 0.05/p < 0.05) in the early morning. However, both the changes in heart rate and PWV, and the differences in blood glucose, lipid and HOMA-R were not significant. Nonetheless, the blood pressure control for 24 hours was better using the combination therapy with losartan at 50 mg/day and HCTZ of 12.5 mg/day than in the treatment with candesartan at 8 mg/day alone. Since losartan decreases uric acid unlike other angiotensin receptor blockers, the combination therapy of losartan and a diuretic can be expected to provide one of the best therapies for essential hypertensive patients.     

Erythromycin enhances delayed gastric emptying in dogs after Roux-Y antrectomy

Delayed gastric emptying occurs in up to 50% of patients after truncal vagotomy and Roux-Y antrectomy and is often resistant to nonsurgical therapy. This study evaluates the effect of erythromycin, metoclopramide, and motilin on delayed gastric emptying in four dogs after Roux-Y antrectomy. Solid food gastric emptying was measured using a radionuclide technique. Study groups were: (1) saline control; (2) erythromycin 1 mg/kg intravenously over 1 hour; (3) erythromycin 3 mg/kg by mouth 45 minutes prior to feeding; (4) metoclopramide 0.6 mg/kg intravenously over 1 hour; and (5) motilin 500 ng/kg intravenously over 1 hour. After Roux-Y antrectomy, saline control dogs had 73% +/- 5% (SEM) gastric retention at 2 hours. After intravenous and oral erythromycin, gastric emptying improved at 2 hours to 27% +/- 6% and 39% +/- 5% (p less than 0.01 compared with control). Erythromycin intravenously and by mouth improved gastric emptying compared with metoclopramide (64% +/- 8%, p less than 0.05). Motilin enhanced gastric emptying to a similar degree as erythromycin, with a 2-hour gastric retention of 37% +/- 4% (NS). Erythromycin improved gastric emptying in dogs with severe Roux-Y gastroparesis and may have clinical application.     

Mild hypothermia improves survival after prolonged, traumatic hemorrhagic shock in pigs

INTRODUCTION: Clinical studies have demonstrated improved survival after cardiac arrest with induction of mild hypothermia (34 degrees C). Infusion of ice-cold saline seems beneficial. The American Heart Association recommends therapeutic hypothermia for comatose survivors of cardiac arrest. For hemorrhagic shock (HS), laboratory studies suggest that mild hypothermia prolongs the golden hour for resuscitation. Yet, the effects of hypothermia during HS are unclear since retrospective clinical studies suggest that hypothermia is associated with increased mortality. Using a clinically relevant, large animal model with trauma and intensive care, we tested the hypothesis that mild hypothermia, induced with intravenous cold saline (ice cold or room temperature) and surface cooling, would improve survival after HS in pigs. METHODS: Pigs were prepared under isoflurane anesthesia. After laparotomy, venous blood (75 mL/kg) was continuously withdrawn over 3 hours (no systemic heparin). At HS 35 minutes, the spleen was transected. At HS 40 minutes, pigs were divided into three groups (n = 8, each): 1) Normothermia (Norm)(38 degrees C), induced with warmed saline; 2) Mild hypothermia (34 degrees C) induced with i.v. infusion of 2 degrees C saline (Hypo-Ice) and surface cooling; and 3) Mild hypothermia (34 degrees C), induced with room temperature (24 degrees C) i.v. saline (Hypo-Rm) and surface cooling. Fluids were given when mean arterial pressure (MAP) was <30 mmHg. At HS 3 hours, shed blood was returned and splenectomy was performed. Intensive care was continued to 24 hours. RESULTS: At 24 hours, there were two survivors in the Norm group, four in the Hypo-Ice group and seven in the Hypo-Rm group (p < 0.05 versus the Norm group, Log Rank). Time required to achieve 34 degrees C was 17 +/- 9 minutes in the Hypo-Ice group and 15 +/- 4 minutes in the Hypo-Rm group (NS). Compared with the Hypo-Rm group, the Hypo-Ice group required less saline during early HS (321 +/- 122 versus 571 +/- 184 mL, p < 0.05). The Hypo-Ice group also had higher lactate levels than the Hypo-Rm group (p < 0.05). Hypothermia did not cause any increase in bleeding compared with normothermia. CONCLUSION: Mild hypothermia during HS, induced by infusion of room temperature saline and surface cooling, improves survival in a clinically relevant model of HS and trauma. However, the use of iced saline in this model had detrimental effects and did not cool the animal more quickly than room temperature fluids. These findings suggest that optimal methods for induction of hypothermia need to be addressed for each potential indication, e.g. cardiac arrest versus HS.     

Resuscitation from hemorrhagic shock. Alterations of the intracranial pressure after normal saline, 3% saline and dextran-40.

Resuscitation from hemorrhagic shock by infusion of isotonic (normal) saline (NS) is accompanied by a transient elevation in intracranial pressure (ICP), although cerebral edema, as measured by brain weights at 24 hours, is prevented by adequate volume resuscitation. The transient increase in ICP is not observed during hypertonic saline (HS) resuscitation. The effect of colloid resuscitation on ICP is unknown. Beagles were anesthetized, intubated, and ventilated, maintaining pCO2 between 30-45 torr. Femoral artery, pulmonary artery, and urethral catheters were positioned. ICP was measured with a subarachnoid bolt. Forty per cent of the dog's blood volume was shed and the shock state maintained for 1 hour. Resuscitation was done with shed blood and a volume of either NS (n = 5), 3% HS (n = 5), or 10% dextran-40 (D-40, n = 5) equal to the amount of shed blood. Intravascular volume was then maintained with NS. ICP fell from baseline values (4.7 +/- 3.13 mmHg) during the shock state and increased greatly during initial fluid resuscitation in NS and D-40 groups, to 16.0 +/- 5.83 mmHg and 16.2 +/- 2.68 mmHg, respectively. ICP returned to baseline values of 3.0 +/- 1.73 mmHg in the HS group with initial resuscitation and remained at baseline values throughout resuscitation. NS and D-40 ICP were greater than HS ICP at 1 hour (p less than .001) and 2 hours (p less than .05) after resuscitation. These results demonstrate that NS or colloid resuscitation from hemorrhagic shock elevates ICP and that HS prevents elevated ICP.     

Valve-sparing aortic root reconstruction in patients with significant aortic insufficiency

BACKGROUND: To assess the feasibility and outcome of the valve-sparing aortic root reimplantation technique in patients with severe preoperative aortic insufficiency (AI). METHODS: Within 8 years we have operated on 158 patients with aneurysms of the ascending aorta using the reimplantation technique. We identified 83 patients with AI grade 3 or 4 (mean 3.1 +/- 0.4) preoperatively (study group). This cohort was compared with 71 patients with AI grade 2 or less (mean 1.3 +/- 0.9; control group) with regard to mortality, operative variables, complications, need for reoperation, postoperative AI, and clinical presentation during follow-up. RESULTS: Patient demographics were comparable in both groups. However, Marfan's syndrome (32% versus 13%, p = 0.006) and acute type A aortic dissection (20% versus 8.4%, p = 0.059) were more frequent in the control group. In addition, bypass (177 +/- 60 minutes versus 160 +/- 36 minutes, p = 0.022) and cross clamp times (133 +/- 34 minutes versus 124 +/- 27 minutes, p = 0.049) were significantly longer in controls. Mortality was low in the study group and comparable with controls (30-day, 3.6% versus 4.2%; during follow-up, 3.8% versus 5.9%; p = not significant [NS]). Reoperation rate was almost identical in both groups (3.8% versus 4.4%, p = NS). Mean grade of AI was significantly higher in the study group early postoperatively (0.31 +/- 0.46 versus 0.18 +/- 0.42, p = 0.049) but comparable at the last visit (0.43 +/- 0.58 versus 0.42 +/- 0.62, p = NS). During follow-up neither thromboembolic complications nor bleeding events were noted in either group. Clinical performance at the last visit revealed no significant difference between the groups. CONCLUSIONS: Preoperative severe aortic insufficiency does not impair the excellent outcome seen after a mean of 3 years of follow-up in patients undergoing the reimplantation technique for valve-sparing aortic root reconstruction.     

Cerebrovascular resuscitation after polytrauma and fluid restriction

BACKGROUND: There are few reproducible models of blast injury, so it is difficult to evaluate new or existing therapies. We developed a clinically relevant polytrauma model to test the hypothesis that cerebrovascular resuscitation is optimized when intravenous fluid is restricted. STUDY DESIGN: Anesthetized swine (42+/-5 kg, n=35) received blasts to the head and bilateral chests with captive bolt guns, followed by hypoventilation (4 breaths/min; FiO(2)=0.21). After 30 minutes, resuscitation was divided into phases to simulate typical prehospital, emergency room, and ICU care. For 30 to 45 minutes, group 1, the control group (n=5), received 1L of normal saline (NS). For 45 to 120 minutes, additional NS was titrated to mean arterial pressure (MAP) > 60 mmHg. After 120 minutes, mannitol (1g/kg) and phenylephrine were administered to manage cerebral perfusion pressure (CPP) > 70 mmHg, plus additional NS was given to maintain central venous pressure (CVP) > 12 mmHg. In group 2 (n=5), MAP and CPP targets were the same, but the CVP target was>8 mmHg. Group 3 (n=5) received 1 L of NS followed only by CPP management. Group 4 (n=5) received Hextend (Abbott Laboratories), instead of NS, to the same MAP and CPP targets as group 2. RESULTS: Polytrauma caused 13 deaths in the 35 animals. In survivors, at 30 minutes, MAP was 60 to 65 mmHg, heart rate was >100 beats/min, PaO(2) was < 50 mmHg, and lactate was>5 mmol/L. In two experiments, no fluid or pressor was administered; the tachycardia and hypotension persisted. The first liter of intravenous fluid partially corrected these variables, and also partially corrected mixed venous O(2), gastric and portal venous O(2), cardiac output, renal blood flow, and urine output. Additional NS (total of 36+/-1 mL/kg/h and 17+/-6 mL/kg/h, in groups 1 and 2, respectively) correlated with increased intracranial pressure to 38+/-4 mmHg (group 1) and 26+/-4 mmHg (group 2) versus 22+/-4 mmHg in group 3 (who received 5+/-1 mL/kg/h). CPP was maintained only after mannitol and phenylephrine. By 5 hours, brain tissue PO(2) was>20 mmHg in groups 1 and 2, but only 6+/-1 mmHg in group 3. In contrast, minimal Hextend (6+/-3 mL/kg/h) was needed; the corrections in MAP and CPP were immediate and sustained, intracranial pressure was lower (14+/-2 mmHg), and brain tissue PO(2) was> 20 mmHg. Neuropathologic changes were consistent with traumatic brain injury, but there were no statistically significant differences between groups. CONCLUSIONS: After polytrauma and resuscitation to standard MAP and CPP targets with mannitol and pressor therapy, we concluded that intracranial hypertension was attenuated and brain oxygenation was maintained with intravenous fluid restriction; cerebrovascular resuscitation was optimized with Hextend versus NS; and longer term studies are needed to determine neuropathologic consequences.