Comparison of three fluid solutions for resuscitation in dengue shock syndrome. Crystalloid versus colloid fluid therapy after cardiac surgery. Cardiac response is greater for colloid than saline fluid loading after cardiac or vascular surgery. Crystalloid versus colloid in fluid resuscitation of patients with severe pulmonary insufficiency. Restoration of volume by crystalloid versus colloid after coronary artery bypass: hemodynamics, lung water, oxygenation, and outcome. Intraoperative colloid administration reduces postoperative nausea and vomiting and improves postoperative outcomes compared with crystalloid administration. A prospective randomized trial evaluating colloid versus crystalloid resuscitation in the treatment of the vascular leak syndrome associated with interleukin-2 therapy. Randomized trial of efficacy of crystalloid and colloid resuscitation on hemodynamic response and lung water following thermal injury. [Preload during spinal anesthesia for cesarean section: comparison between crystalloid and colloid solutions.]. Hemostatic changes after crystalloid or colloid fluid administration during major orthopedic surgery: the role of fibrinogen administration. Randomized evaluation of fluid resuscitation with crystalloid (saline) and colloid (polymer from degraded gelatin in saline) in pediatric septic shock. [Tactics of infusion therapy in the acute period of intracranial hemorrhages]. Use of modified fluid gelatin and hydroxyethyl starch for colloidal volume replacement in major orthopaedic surgery. Effects of dextran and crystalloids on subcutaneous oxygen tension and collagen accumulation. A randomized study in surgical patients. Fluid therapy with Ringer's solution versus Haemaccel following coronary artery bypass surgery. The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients. Fluid balance and pulmonary functions during and after coronary artery bypass surgery: Ringer's acetate compared with dextran, polygeline, or albumin. Crystalloid vs. colloid resuscitation: is one better? A randomized clinical study. Efficacy of hetastarch in the resuscitation of patients with multisystem trauma and shock. The significance of colloid osmotic pressure measurement after crystalloid and colloid infusions. Fluid resuscitation in the management of early septic shock (FINESS): a randomized controlled feasibility trial. Effects of colloid or crystalloid administration on pulmonary extravascular water in the postoperative period after coronary artery bypass grafting. Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. Acute management of dengue shock syndrome: a randomized double-blind comparison of 4 intravenous fluid regimens in the first hour. A randomized clinical trial of 10% pentastarch (low molecular weight hydroxyethyl starch) versus 5% albumin for plasma volume expansion after cardiac operations. Colloid solutions in the critically ill. A randomised comparison of albumin and polygeline. 1. Outcome and duration of stay in the intensive care unit. Hypertonic saline fluid therapy following surgery: a prospective study. Treatment of faecal impaction with polyethelene glycol plus electrolytes (PGE + E) followed by a double-blind comparison of PEG + E versus lactulose as maintenance therapy. Effects of three colloid solutions on plasma volume and hemodynamics after coronary bypass surgery. Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study. A comparison of prelubricated hydrophilic and non-hydrophilic polyvinyl chloride catheters for urethral catheterization. The effects of perioperatively administered crystalloids and colloids on concentrations of molecular markers of activated coagulation and fibrinolysis. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. Long-term results of sealed capsule irrigation using distilled water to prevent posterior capsule opacification: a prospective clinical randomised trial. Colloid vs. crystalloid preloading to prevent maternal hypotension during spinal anesthesia for elective cesarean section. Short-term effectiveness of different volume replacement therapies in postoperative hypovolaemic patients. Custom-tailored hemodilution with albumin and crystalloids in acute ischemic stroke. A multicenter trial for resuscitation of injured patients with 7.5% sodium chloride. The effect of added dextran 70. The Multicenter Group for the Study of Hypertonic Saline in Trauma Patients. Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. Protocol-guided diuretic management: comparison of furosemide by continuous infusion and intermittent bolus. Tolerance and efficacy of polyethylene glycol 3350/electrolyte solution versus lactulose in relieving opiate induced constipation: a double-blinded placebo-controlled trial. Crystalloid preload versus rapid crystalloid administration after induction of spinal anaesthesia (coload) for elective caesarean section. Advantages of dextran 70 over Ringer acetate solution in shock treatment and in prevention of adult respiratory distress syndrome. A randomized study in man after traumatic-haemorrhagic shock. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. Prospective study of replacing administration sets for intravenous therapy at 48- vs 72-hour intervals. 72 hours is safe and cost-effective. Response of extravascular lung water to intraoperative fluids. Replacement of major surgical blood loss by hypo-oncotic or conventional plasma substitutes. A novel hydroxyethyl starch (Voluven) for effective perioperative plasma volume substitution in cardiac surgery. Hypertonic saline-dextran solutions for the prehospital management of traumatic hypotension. Hemodialysis infection prevention with polysporin ointment. Comparison of a low dose polyethylene glycol electrolyte solution with lactulose for treatment of chronic constipation. Furosemide in hyaline membrane disease. Comparison of 6% hydroxyethyl starch 130/0.4 and saline solution for resuscitation of the microcirculation during the early goal-directed therapy of septic patients. Hypertonic sodium lactate versus lactated ringer's solution for intravenous fluid therapy in operations on the abdominal aorta. A randomized, controlled pilot study of the safety and efficacy of 4% icodextrin solution in the reduction of adhesions following laparoscopic gynaecological surgery. Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage : a randomized controlled trial. Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study. 3% NaCl and 7.5% NaCl/dextran 70 in the resuscitation of severely injured patients. A randomized double-blind placebo-controlled trial of cyclosporine in steroid-resistant idiopathic focal segmental glomerulosclerosis in children. Effects of maintaining normal plasma colloid osmotic pressure on renal function and excretion of sodium and water after major surgery. A randomized study. [Therapy of rheumatic disease with a hydroxyethylsalicylate gel. Results of 2 clinical studies of effectiveness and bioavailability]. Hydroxyethyl starch versus albumin for colloid infusion following cardiopulmonary bypass in patients undergoing myocardial revascularization. Comparison of perindopril and amlodipine in cyclosporine-treated renal allograft recipients. Optimal fluid management after aortic reconstruction: a prospective study of two crystalloid solutions. Failure of intraperitoneal adjuncts to improve the outcome of pelvic operations in young women. Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial. Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study. Fluid resuscitation in circulatory shock: a comparison of the cardiorespiratory effects of albumin, hetastarch, and saline solutions in patients with hypovolemic and septic shock. Treatment of hemorrhagic shock with intraosseous or intravenous infusion of hypertonic saline dextran solution. Converting-enzyme inhibitor versus calcium antagonist in cyclosporine-treated renal transplants. Ringer's lactate with or without 3% dextran-60 as volume expanders during abdominal aortic surgery. A total balanced volume replacement strategy using a new balanced hydoxyethyl starch preparation (6% HES 130/0.42) in patients undergoing major abdominal surgery. Plasma infusion for hemolytic-uremic syndrome in children: results of a multicenter controlled trial. Randomised controlled trial of colloid infusions in hypotensive preterm infants. Hypertonic saline for intraoperative fluid therapy in transurethral resection of the prostate. [Parenteral antibiotic prophylaxis or oral antimicrobial bowel preparation for colorectal surgery (author's transl)]. Treatment of severe preeclampsia with antithrombin concentrate: results of a prospective feasibility study.
Dengue shock syndrome is characterized by severe vascular leakage and disordered hemostasis and progresses to death in 1 to 5 percent of cases. Although volume replacement is recognized as the critical therapeutic intervention, World Health Organization management guidelines remain empirical rather than evidence-based.
                We performed a double-blind, randomized comparison of three fluids for initial resuscitation of Vietnamese children with dengue shock syndrome. We randomly assigned 383 children with moderately severe shock to receive Ringer's lactate, 6 percent dextran 70 (a colloid), or 6 percent hydroxyethyl starch (a colloid) and 129 children with severe shock to receive one of the colloids. The primary outcome measure was requirement for rescue colloid at any time after administration of the study fluid.
                Only one patient died (<0.2 percent mortality). The primary outcome measure--requirement for rescue colloid--was similar for the different fluids in the two severity groups. The relative risk of requirement for rescue colloid was 1.08 (95 percent confidence interval, 0.78 to 1.47; P=0.65) among children with moderate shock who received Ringer's lactate as compared with either of the colloid solutions, 1.13 (95 percent confidence interval, 0.74 to 1.74; P=0.59) among children who received dextran as compared with starch in the group with severe shock, and 0.88 (95 percent confidence interval, 0.66 to 1.17; P=0.38) among children who received dextran as compared with starch in the combined analysis. Although treatment with Ringer's lactate resulted in less rapid improvement in the hematocrit and a marginally longer time to initial recovery than did treatment with either of the colloid solutions, there were no differences in all other measures of treatment response. Only minor differences in efficacy were detected between the two colloids, but significantly more recipients of dextran than of starch had adverse reactions. Bleeding manifestations, coagulation derangements, and severity of fluid overload were similar for all fluid-treatment groups.
                Initial resuscitation with Ringer's lactate is indicated for children with moderately severe dengue shock syndrome. Dextran 70 and 6 percent hydroxyethyl starch perform similarly in children with severe shock, but given the adverse reactions associated with the use of dextran, starch may be preferable for this group.
                Copyright 2005 Massachusetts Medical Society. Differences in hemodynamic stability and fluid requirements were examined in patients randomly assigned to receive either normal saline crystalloid solution (N = 10) or hetastarch colloid solution (N = 11) after coronary artery bypass or valve operation. Both solutions were administered in the same manner for 8 hours after surgery, with hourly assessment of hemodynamic parameters and intake/output data. Infusion rates and 8-hour intake were higher for the group receiving normal saline solution (p less than 0.001), as was postoperative weight gain (p less than 0.01), although urine and chest tube outputs did not differ. Despite lower filling pressures, subjects receiving hetastarch exhibited higher systolic blood pressures and cardiac outputs (p less than 0.05). Hematocrits on postoperative day 1 were lower in the group given hetastarch (p less than 0.001), suggesting prolonged intravascular expansion. The subjects given hetastarch also required significantly less time in the intensive care unit (p less than 0.001). Thus, cardiac surgical patients receiving colloids exhibited reduced fluid requirements, superior hemodynamic performance, and shortened intensive care stay when compared with those given crystalloid resuscitation. To study the effects on volume expansion and myocardial function of colloids or crystalloids in the treatment of hypovolaemic hypotension after cardiac and major vascular surgery.
                A single-centre, single-blinded, randomized clinical trial at the intensive care unit of a university hospital.
                Patients (n=67) were subjected to a 90-min filling pressure-guided fluid challenge with saline 0.9% or the colloids gelatin 4%, hydroxyethyl starch 6% or albumin 5%. Biochemical variables and haemodynamics (transpulmonary thermodilution) were measured.
                An amount of 1800 (1300-1800) ml of saline or 1600 (750-1800) ml of colloid solution (P< 0.005) was infused. Colloid osmotic pressure (COP) decreased in the saline group and increased in the colloid groups (P< 0.001). Plasma volume increased by 3.0% (-18 to 24) in the saline versus 19% (-11 to 50) in the colloid groups (P< 0.001). Cardiac index increased by median 13% (ns) in the saline group and by 22% in the colloid groups (P<0.005). The rise in left ventricular stroke work index was greater in the colloid than in the saline groups. The different colloids were equally effective. The rise in cardiac index related to the rise in plasma volume and global end-diastolic volume, confirming plasma volume and preload augmentation by the fluid loading.
                After cardiac or major vascular surgery, the pressure- and time-guided fluid response is dependent on the type of fluid used. Colloid fluid loading leads to a greater increase in preload-recruitable cardiac and left ventricular stroke work indices than that with saline, because of greater plasma volume expansion following an increase in plasma COP. Forty-six patients with severe pulmonary insufficiency were prospectively studied to compare the effects of resuscitation with either crystalloid or colloid. By random number, 26 patients received RL and 20 patients received 5 per cent ALB to maintain hemodynamic stability. Groups were comparable with respect to the cause of pulmonary insufficiency, age and sex. For the duration of the study and at 48 hours, there was no statistically significant difference between groups with respect to the following: cardiac index, colloid osmotic pressure (COP), pulmonary capillary wedge pressure (PCWP), COP-PCWP gradient, right and left ventricular stroke work indices, and amount of constant positive airway pressure required for treatment. Both groups had a significant improvement in intrapulmonary shunt (Qs/Qt) after 24 hours of treatment. The Qs/Qt in the ALB group was significantly lower than the RL group at the termination of the study, but this did not affect outcome. The RL group required more fluid than the ALB group, but the difference was not statistically significant. No clinical advantage was found for either solution in this study. We compared Ringer's acetate-gluconate solution with 6% dextran-70 infused during rewarming after coronary bypass surgery. In a randomized study, 18 patients received 56 +/- 15 ml/kg of crystalloid (group 1), and 14 patients received 16 +/- 6 ml/kg of dextran (group 2). Data were taken at the following intervals: 4 to 5 h after terminating the cardiopulmonary bypass, after rewarming, the next morning on controlled ventilation and continuous positive airway pressure (CPAP) breathing, and after extubation. The patients were followed for 14 days. Prophylactic nitroglycerin infusion may have increased the need for plasma expansion. After volume loading, the stroke index increased in both groups, but the left ventricular stroke work index increased in group 2 only. After transition to the CPAP mode, hydrostatic pressures increased, more in group 2, doubling the pulmonary shunt flow. Pulmonary extravascular thermal volume did not change in either group. We conclude that hemodynamic stability occurred faster with dextran, and ventilatory weaning was somewhat easier with crystalloid. The debate over colloid versus crystalloid as the best solution for intraoperative fluid resuscitation is not resolved. Published studies have shown that mortality is not related to the specific fluid used for resuscitation. In addition, the quality of postoperative recovery between colloid and crystalloid has not been well investigated. In a prospective, blinded fashion, we investigated the effects of colloid and crystalloid resuscitation on nausea and vomiting and on the postoperative patient recovery profile. Patients undergoing major elective noncardiac surgery were randomized to receive 6% hetastarch in saline (HS-NS), 6% hetastarch in balanced salt (HS-BS), or lactated Ringer's solution (LR) on the basis of a fluid administration algorithm. The anesthetic was standardized. Hemodynamic targets included maintenance of arterial blood pressure, heart rate, and urine output within a predefined range. A postoperative morbidity survey was performed at baseline and daily after surgery. Ninety patients participated in the study, with 30 patients in each group. The amounts of study fluid (mean +/- SD) administered were 1301 +/- 1079 mL, 1448 +/- 759 mL, and 5946 +/- 1909 mL for the HS-NS, HS-BS, and LR groups, respectively (P < 0.05, HS-NS and HS-BS versus LR). Both the HS-NS and HS-BS (colloid) groups had a significantly less frequent incidence of nausea and vomiting, use of rescue antiemetics, severe pain, periorbital edema, and double vision. We concluded that intraoperative fluid resuscitation with colloid, when compared with crystalloid administration, is associated with an improvement in the quality of postoperative recovery. Interleukin-2 (IL-2)-based therapy induces a vascular leak syndrome (VLS), manifested by hypotension, tachycardia, and oliguria, as is also seen with septic shock. The optimal method for treating such VLS is not known. A prospective randomized trial was undertaken to compare crystalloid and colloid fluid resuscitation for patients receiving bolus IL-2-based therapy for metastatic cancer. All patients received maintenance crystalloid fluid administration and were randomized to receive crystalloid (0.9% normal saline) or colloid (5% human serum albumin) fluid boluses to maintain acceptable vital signs and urine output. Patients refractory to fluid boluses were given dopamine for oliguria and/or phenylephrine for hypotension. Of 107 patients who completed one cycle of therapy on study, 76 completed a full treatment course (two cycles) on study. The total number of saline and albumin fluid boluses given were 9.5 +/- 0.9 versus 7.7 +/- 0.7 (p = 0.36, n = 107) for the first cycle and 19.2 +/- 1.8 versus 16.1 +/- 1.6 (p = 0.33, n = 76) for a complete course, respectively. Although patients receiving saline boluses had significantly more oliguria during a course of therapy, weight gain, number of IL-2 doses, tachycardia, hypotension, vasopressor use, hospital stay, and clinical response rates did not significantly differ between arms. Changes in hematocrit, hemoglobin, protein, albumin, blood urea nitrogen (BUN), and creatinine were analyzed, and patients receiving crystalloid showed greater decreases in albumin (p < 0.0001) and total protein (p < 0.05) as expected. A 40-fold greater cost associated with albumin suggested that crystalloid resuscitation be used to treat the VLS associated with IL-2 therapy.(ABSTRACT TRUNCATED AT 250 WORDS) To assess the effects of crystalloid and colloid resuscitation on hemodynamic response and on lung water following thermal injury, 79 patients were assigned randomly to receive lactated Ringer's solution or 2.5% albumin-lactated Ringer's solution. Crystalloid-treated patients required more fluid for successful resuscitation than did those receiving colloid solutions (3.81 vs. 2.98 ml/kg body weight/% body surface burn, p less than 0.01). In study phase 1 (29 patients), cardiac index and myocardial contractility (ejection fraction and mean rate of internal fiber shortening, Vcf) were determined by echocardiography during the first 48 hours postburn. Cardiac index was lower in the 12- to 24-hour postburn interval in the crystalloid group, but this difference between treatment groups had disappeared by 48 hours postburn. Ejection fractions were normal throughout the entire study, while Vcf was supranormal (p less than 0.01 vs. normals) and equal in the two resuscitation groups. In study phase 2 (50 patients), extravascular lung water and cardiac index were measured by a standard rebreathing technique at least daily for the first postburn week. Lung water remained unchanged in the crystalloid-treated patients (p greater than 0.10), but progressively increased in the colloid-treated patients over the seven day study (p less than 0.0001). The measured lung water in each treatment group was significantly different from one another (p less than 0.001). Cardiac index increased progressively and identically in both treatment groups over the study period (p less than 0.01). These data refute the existence of myocardial depression during postburn resuscitation and document hypercontractile left ventricular performance. The addition of colloid to crystalloid resuscitation fluids produces no long lasting benefit on total body blood flow, and promotes accumulation of lung water when edema fluid is being reabsorbed from the burn wound. Maternal hypotension is the most common complication following spinal anesthesia for cesarean section. This study aimed at comparing the incidence of hypotension and the need for vasopressors in patients submitted to cesarean section under spinal anesthesia following preload with either crystalloid or colloid (modified fluid gelatin).
                Participated in this prospective study 50 term pregnant patients, physical status ASA I, submitted to cesarean section under spinal anesthesia. Patients were randomly allocated into two groups receiving preload as follows: Crystalloid group, 10 mL.kg-1 lactated Ringer; Colloid group, 10 mL.kg-1 colloid (modified fluid gelatin). Control blood pressure was defined as the mean of three successive systolic blood pressure (SBP) values. SBP was measured at 1-minute intervals and 0.2 mg intravenous bolus of metaraminol was administered for SBP decrease above 10% of control blood pressure, and 0.4 mg bolus of the same drug for SBP decrease above 20% of control. Apgar score was evaluated after delivery and umbilical artery blood was sent for analysis. Modified Student's t test was used for statistical analysis and p < 0.05 was considered statistically significant.
                Hypotension 10% (100% and 100% of patients); hypotension 20% (72% and 72% of patients), nausea (4% and 8% of patients); vasopressor consumption (1.67+/- 0.89 mg and 1.88 +/- 0.74 mg) and umbilical artery pH (7.25 +/- 0.04 and 7.26 +/- 0.04), in Crystalloid and Colloid groups, respectively, were similar.
                In the conditions of this study, colloid (modified fluid gelatin) was equivalent to crystalloid (lactate Ringer) in preventing or decreasing the incidence of hypotension in patients submitted to cesarean section under spinal anesthesia. To explore whether disturbed fibrin polymerization is the main problem underlying dilutional coagulopathy and can be reversed by fibrinogen administration, we conducted a prospective study using modified thrombelastography (ROTEM).
                Sixty-six orthopedic patients randomly received modified gelatin solution, hydroxyethyl starch 130/0.4, or exclusively Ringer lactate solution. ROTEM analysis was performed, concentrations of coagulation factors and markers of thrombin generation were measured. Fibrinogen concentrate (Hemocomplettan) was administered (30 mg/kg) when thrombelastographically measured fibrinogen polymerization was critically decreased.
                The alpha angle, clot firmness, and fibrinogen polymerization (median [min to max]) significantly decreased in the patients receiving hydroxyethyl starch (area under the curve minus baseline (-5 [-9 to -2]), followed by gelatin solution (-3 [-8 to 0]), with the least reductions seen for Ringer lactate solution (-2 [- 4 to 1]) (colloids versus Ringer lactate P < 0.0001). Thirteen patients in the colloid groups but none in the Ringer lactate group needed fibrinogen concentrate to maintain borderline clot firmness. Activity of FVII, FVIII, FIX, and von Willebrand ristocetin activity decreased significantly with colloids. Thrombelastographically measured coagulation time, molecular markers of thrombin generation, and activity of all other coagulation factors were comparable in all groups.
                Disturbance of fibrinogen/fibrin polymerization is the primary problem triggering dilutional coagulopathy during major orthopedic surgery. The magnitude of clot firmness reduction is determined by the type of fluid used, with hydroxyethyl starch showing the most pronounced effects. These undesirable effects of intravascular volume therapy can be reversed by increasing fibrinogen concentration by administering fibrinogen concentrate, even during continuing blood loss and intravascular volume replacement. To compare the efficacy of crystalloid (Normal saline) and colloid (polymer from degraded Gelatin in saline Haemaccel) intravenous fluid in restoration of circulating volume in children with septic shock.
                Prospective, randomized, open-label trial.
                Pediatric Emergency and Intensive Care Unit of a tertiary care referral and teaching hospital. SUBJECTS AND INCLUSION CRITERIA: Sixty patients, between 1 month to 12 years of age, with septic shock, without clinical evidence of organ failure at admission or underlying immunodeficiency.
                Resuscitation with normal saline or polymer from degraded gelatin (Haemaccel) in the boluses rate of 20 mL/kg till hemodynamic stabilization or if central venous pressure (CVP) exceeded 10 mmHg (fluid requirement beyond 40 mL/kg guided by BP and CVP).
                Hemodynamic parameters (heart rate, capillary filling time, pulse volume, and blood pressure) were recorded before and during resuscitation, and then 2 hourly for 12 hours. Central venous pressure line was placed within first hour, soon after starting fluids. Estimation of plasma volume and body water was done at the end of first hour of fluid resuscitation.
                Hemodynamic stabilization (heart rate, capillary refill time, systolic BP in normal range), plasma volume at the end of fluid resuscitation and incidence of organ dysfunction.
                31 patients were randomized to normal saline and 29 to gelatin polymer. Both the groups were similar with respect to age, gender, primary diagnosis, initial hemodynamic parameters and PRISM score. Pneumonia (n = 22; 36%), gut-associated sepsis (n = 13), and dengue hemorrhagic fever (n = 11) were the common primary diagnosis. Initial hemodynamic stabilization was achieved in all. The mean (SD plasma volume (saline--53.4 (2.0 mL/kg, gelatin polymer--53.2 (1.9 mL/kg), extracellular fluid volume, total body water and interstitial fluid volume at the end of first hour of resuscitation were similar. The requirement of inotropes, incidence of organ dysfunction and case fatality rate (Saline--29%, gelatin polymer--31%), were similar in two groups.
                Both normal saline and gelatin polymer solution were equally effective as resuscitation fluid with respect to restoration of plasma volume and hemodynamic stability. Normal saline upto 110 mL/kg, and gelatin polymer solution upto 70 mL/kg may be required in first hour for successful fluid resuscitation of septic shock in children. The paper deals with the determination of infusion therapy tactics in critically ill patients with intracranial hemorrhages on the basis of invasive measurements of systemic hemodynamics. The routine hemodynamic parameters (blood and central venous pressures, heart rate) are noted to fail to assess the volemic status of the patients in full. Unlike the use of colloidal solutions, infusion therapy with physiological sodium chloride is not shown to correct systemic hemodynamics. It has been ascertained that in acute intracranial hemorrhages, infusion therapy with crystalloidal solutions leads to impaired pulmonary gas exchange and increased pulmonary extravascular fluid and the use of a combination of crystalloidal solutions and a colloidal agent in a 1:1 ratio can correct the volemic status of the patients and is not followed by lung dysfunctions. We have compared 6% hydroxyethyl starch (HES 200/0.5) with 3% modified fluid gelatin (MFG) for volume replacement in major orthopaedic surgery and studied the effects on haemodynamic state, colloid osmotic pressure, blood clotting and plasma homeostasis. Using a controlled, randomized, single-blind clinical design, we studied 46 consecutive patients undergoing major elective orthopaedic hip surgery. The two groups were comparable in age, body weight and duration of surgery. Patients were maintained haemodynamically stable using both HES and MFG over the entire study. Fluid balance and colloidal replacement volumes were comparable in both groups (median perioperative infusion volume: HES 2500 ml, MFG 2400 ml). Laboratory variables were not clinically different. We conclude that both colloidal solutions were comparable in volume efficacy and effects on plasma oncotic pressure, clotting and plasma homeostasis. In the small number of patients studied, 6% HES 200/0.5 was found to be safe when administered in amounts corresponding to the currently accepted maximum daily dose in Germany and France of 33 ml/kg body weight and 2.0 g/kg body weight, respectively. Twenty-nine patients, subjected to major abdominal surgery, were randomized to different types of postoperative fluid replacement, given on the basis of subcutaneous oxygen tension measurements (PscO2). One regimen consisted of crystalloids, the other of a combination of crystalloids and colloids (dextran 70). Perioperative fluid replacement was given according to clinical criteria and postoperatively according to polarographic PscO2 measurements. PscO2 was measured by a silicone catheter implanted in the upper arm. Two tubes of expanded polytetrafluoroethylene (ePTFE) were implanted next to the silicon catheter. They were removed on day 5 and 7, and analysed for hydroxyproline content. Total postoperative fluid support was equal in the two groups, and so was the hydroxyproline content on day 7. In conclusion, postoperative fluid substitution with dextran has no advantages over crystalloids only, with regard to granulation tissue formation if postoperative fluid support is optimum, according to PscO2 measurements. Crystalloid and colloid infusion can be used in volume therapy following heart surgery. In this prospective, randomised study we compared Ringer's solution (group R) to Haemaccel (group H) following coronary artery bypass grafting.
                A stringent protocol for adjusting the infusion rate was used. Haemodynamic parameters and pulmonary function were evaluated as well as chest tube drainage. The double-indicator dilution method was used to measure total blood volume index (TBVI), intrathoracic blood volume index (ITB-VI) and extravascular lung water index (EVLWI).
                Haemodynamic stability was achieved in both groups throughout the study period, as judged from mean arterial pressure, central venous pressure, pulmonary capillary wedge pressure, and cardiac index. However, the total volume infused was significantly higher in group R. TBVI and ITBV were higher in group H, although only significant at 8 h for TBVI. Pulmonary function was similar in both groups. There was no significant difference in EVLWI, pulmonary shunt fraction, and time on mechanical ventilation. Likewise, chest tube drainage was not significantly different in both groups.
                We conclude that volume therapy with Haemaccel following heart surgery requires less volume and achieves better filling of the circulation compared to Ringer's solution. The IV administration of sodium chloride solutions may produce a metabolic acidosis and gastrointestinal dysfunction. We designed this trial to determine whether, in elderly surgical patients, crystalloid and colloid solutions with a more physiologically balanced electrolyte formulation, such as Hartmann's solution and Hextend, can provide a superior metabolic environment and improved indices of organ perfusion when compared with saline-based fluids. Forty-seven elderly patients undergoing major surgery were randomly allocated to one of two study groups. Patients in the Balanced Fluid group received an intraoperative fluid regimen that consisted of Hartmann's solution and 6% hetastarch in balanced electrolyte and glucose injection (Hextend). Patients in the Saline group were given 0.9% sodium chloride solution and 6% hetastarch in 0.9% sodium chloride solution (Hespan). Biochemical indices and acid-base balance were determined. Gastric tonometry was used as a reflection of splanchnic perfusion. Postoperative chloride levels demonstrated a larger increase in the Saline group than the Balanced Fluid group (9.8 vs 3.3 mmol/L, P = 0.0001). Postoperative standard base excess showed a larger decline in the Saline group than the Balanced Fluid group (-5.5 vs -0.9 mmol/L, P = 0.0001). Two-thirds of patients in the Saline group, but none in the Balanced Fluid group, developed postoperative hyperchloremic metabolic acidosis (P = 0.0001). Gastric tonometry indicated a larger increase in the CO2 gap during surgery in the Saline group compared with the Balanced Fluid group (1.7 vs 0.9 kPa, P = 0.0394). In this study, the use of balanced crystalloid and colloid solutions in elderly surgical patients prevented the development of hyperchloremic metabolic acidosis and resulted in improved gastric mucosal perfusion when compared with saline-based solutions.
                This prospective, randomized, blinded trial showed that, in elderly surgical patients, the use of balanced IV solutions can prevent the development of hyperchloremic metabolic acidosis and provide better gastric mucosal perfusion compared with saline-based fluids. The effects on fluid balance, pulmonary functions and economics were evaluated in a randomized comparison of one colloid free and three colloid containing fluid regimens, for 48 hours during and after coronary artery bypass (CAB) surgery. A standard regimen for anaesthesia, extracorporeal circulation and monitoring was used. Only Ringer's acetate (RAc) was used as priming solution for extracorporeal circulation. Forty patients were randomized to receive either RAc, polygeline 35 mg.ml-1 (Haemaccel), dextran 70 (Macrodex) 60 mg.ml-1, or albumin 40 mg.ml-1 in saline whenever fluid volume was needed to stabilize haemodynamics. At the end of the operation, fluid retention was significantly lower in patients receiving polygeline and dextran 70, compared with patients receiving RAc. At 48 hours, however, there were no differences in cumulative fluid balance. Patients in the colloid groups postoperatively had a higher serum colloid osmotic pressure (s-COP), but a higher net lung capillary filtration pressure (delta P) only on the second postoperative day than the RAc group. However, this did not adversely affect intrapulmonary venous admixture, arterial oxygen tension, or time on respirator in the RAc group compared with the colloid groups. The most expensive colloid fluid regimen (albumin) cost about 230 US$ more per patient than the RAc fluid regimen. We conclude that Ringer's acetate for volume replacement to stabilize haemodynamics during and after CAB surgery is associated with increased fluid retention only during the intraoperative period, compared with dextran 70 or polygeline, and with a lower serum colloid osmotic pressure and net lung capillary filtration pressure postoperatively, compared with all three colloid groups. This does not affect pulmonary functions adversely.(ABSTRACT TRUNCATED AT 250 WORDS) The effects of hemodynamic resuscitation with protein-containing or balanced salt solution were studied prospectively in 29 patients undergoing abdominal aortic surgery. Blood loss was replaced with packed red cells and extracellular volume with either Ringer's Lactate (RL) or 5% albumin in Ringer's lactate (ALB). Fluids were given to maintain the pulmonary capillary wedge pressure (PCWP) equal to or within 5 torr above preoperative (PO) levels, the cardiac output (CO) equal to or greater than preoperative values, and the urine output at least 50 ml/hr. Serum colloid osmotic pressure (COP), CO, PCWP, the gradient between COP and PCWP (COP-PCWP), and intrapulmonary shunt (Qs/Qt) were measured PO, intraoperatively (IO), and daily for 3 days. The measured variables were similar PO in both groups. Operation time, estimated blood loss, and transfusions were similar. Total fluids received for resuscitation (day of operation) was 11.3 +/- 0.8 liters (RL) and 6.2 +/- 0.4 liters (ALB). Fluid balance at the end of resuscitation was 8.4 +/- 0.8 liters (RL) and 3.4 +/- 0.5 liters (ALB). Maximum decrease in COP was 40% (P less than 0.001) in the RL group and was insignificant in the ALB group. The COP-PCWP decreased from 11 +/- 1 to 2 +/- 1 in RL (P less than 0.001) and insignificantly in ALB. Qs/Qt increased slightly in both groups following operation but was not different between groups. Fluid balance, total fluid infused, sodium balance, total sodium infused, COP, or COP-PCWP did not significantly correlate with Qs/Qt. Two patients in the ALB group experienced pulmonary edema associated with normal COPs and elevated PCWPs. There were no cases of pulmonary edema associated with low COPs and normal PCWPs in the crystalloid group. These data seriously question the necessity to maintain COP by using protein-containing solutions during acute hemodynamic resuscitation. When titrated to physiological end points, even large volumes of balanced salt solutions are tolerated well. A prospective trial of 6% hetastarch (HES) v 5% plasma protein fraction (PPF) as the colloid component of intravenous (IV) fluid resuscitation was conducted in 32 patients with multisystem trauma and/or hemorrhagic shock. Patient age, mechanism and pattern of injury, and IV fluid requirements were similar in both groups. No intergroup differences were noted in indexes of hepatic, pulmonary, or renal function or in the incidence of infection. The frequency of other complications, including bleeding diatheses, and mortality were identical in the two groups. Although this investigation should be viewed as a pilot study, our results suggest that, compared with PPF, HES in large volumes is a safe, effective colloid solution in the resuscitation of patients with multisystem trauma and/or hemorrhagic shock. Further study of HES in a larger number of patients is warranted by these findings. Colloid osmotic pressure (COP) was followed postoperatively in 55 randomized patients. After minor operations and short-term infusion therapy only small changes of the COP could be observed and it was concluded that after such operations COP measurement is unnecessary. After major surgical interventions, however, COP measurement gave valuable hints. It was shown that even in the case of moderate blood loss replaced by crystalloids an abnormally low COP did not occur. The same applied also to preoperative hemodilution. It was unnecessary to substitute the withdrawn blood with a colloid solution. In addition, COP measurement helped to avoid expensive albumin administrations, and indicated colloid overload in cases of pulmonary edema. It is unknown whether fluid resuscitation with colloid or crystalloid in patients with severe sepsis or septic shock is associated with an improvement in clinical outcome. This randomized controlled trial determined the feasibility of conducting a large trial testing resuscitation with pentastarch vs normal saline in early septic shock, powered for a difference in mortality.
                At three Canadian and one New Zealand academic centre, 40 patients with early septic shock defined by at least two systemic inflammatory response syndrome criteria, infectious source, and persistent hypotension after >or= 1 L of crystalloid fluid were recruited. Feasibility measures were patient recruitment, blinding of the study fluids, and acceptability of the goal directed algorithms. Boluses of blinded normal saline or pentastarch (500 mL - maximum 3 L or 28 mL x kg(-1)) were administered within goal directed care for the first 12 hr.
                Of 161 patients screened, 121 were excluded and 40 patients were enrolled, for a recruitment rate of 0.75 patients/site/month. Only 57% of physicians and 54% of nurses correctly guessed the study fluid (P = 0.46 and P = 0.67, respectively). The goal directed algorithms were acceptable to 97% of physicians.
                The ability to recruit patients in this pilot randomized controlled trial was below expectations. Blinding of study fluids was adequate, and resuscitation algorithms were acceptable to most physicians. Methods to improve recruitment are required to enhance the feasibility of conducting a multicentre fluid resuscitation trial in early septic shock. The effect of postoperative fluid management on pulmonary extravascular thermal volume (ETVL) as in index of pulmonary extravascular water after coronary artery bypass grafting was compared, using the thermal-dye technique, among five patients who received 5% albumin (group A), five patients who received 6% hydroxyethyl starch (group H), and five who received lactated Ringer's solution (group C). Intraoperatively, all patients received lactated Ringer's solution intravenously, and the cardiopulmonary bypass (CPB) circuit prime included 5% albumin. No statistically significant changes in ETVL occurred postoperatively in any group, nor did ETVL differ significantly between groups. After CPB, colloid osmotic pressure (COP) significantly decreased and pulmonary artery wedge pressure (WP) and the WP-COP gradient significantly increased in each group, implying an increase in transcapillary fluid flux. Cardiac index changed variably. Pulmonary shunt fraction (Qsp/Qt) did not change in groups A and C but decreased during CPB in group H (from 0.22 +/- 0.03 to 0.16 +/- 0.11). Postoperatively, patients in the three groups received similar volumes of fluids and had similar perioperative weight gains. By the next morning (AM1), COP increased in all groups, returning to levels noted before CPB in group C, and exceeding these levels in groups A and H. Wedge pressure was similar in all three groups on AM1. PaO2 decreased significantly, and alveolar-arterial oxygen partial pressure difference increased significantly in all groups on AM1. In Group H, Qsp/Qt returned to levels observed before CPB by AM1 (0.27 +/- 0.09). We conclude that in patients without postoperative increases in WP, ETVL changes minimally during CPB and is not influenced by the type of fluid administered as the primary volume replacement in the postoperative period. Cisplatin, mitolactol (dibromodulcitol), and ifosfamide have been the most active single agents in squamous carcinoma of the cervix identified so far by the Gynecologic Oncology Group (GOG). Combinations of cisplatin plus ifosfamide and cisplatin plus mitolactol are prospectively compared with cisplatin alone.
                Patients were randomized to receive cisplatin 50 mg/m2 or the same dose of cisplatin plus mitolactol (C + M) 180 mg/m2 orally on days 2 to 6, or cisplatin plus ifosfamide (CIFX) 5 g/m2 given as a 24-hour infusion plus mesna 6 g/m2 during and for 12 hours after the ifosfamide infusion, every 3 weeks for up to six courses. Of 454 patients entered, 438 were eligible and analyzed for response and survival.
                CIFX had a higher response rate (31.1% v 17.8%, p = .004) and longer progression-free survival (PFS) time (P = .003) compared with cisplatin alone. The median times to progression or death were 4.6 and 3.2 months, respectively. C + M showed no significant improvement in these parameters compared with cisplatin alone. Survival was associated with initial performance score (PS; 0 was more favorable; P < .001) and with age (younger was unfavorable, P = .025). There was no significant difference in overall survival between cisplatin and either of the combinations. Leukopenia, renal toxicity, peripheral neurotoxicity, and CNS toxicity were more frequent with CIFX (P < .05).
                CIFX improved the response rate and PFS duration in advanced cervix cancer compared with cisplatin alone, but at the cost of greater toxicity and with no improvement in survival. Dengue hemorrhagic fever is an important cause of morbidity among Asian children, and the more severe dengue shock syndrome (DSS) causes a significant number of childhood deaths. DSS is characterized by a massive increase in systemic capillary permeability with consequent hypovolemia. Fluid resuscitation is critical, but as yet there have been no large trials to determine the optimal fluid regimen. We undertook a randomized blinded comparison of 4 fluids (dextran, gelatin, lactated Ringer's, and "normal" saline) for initial resuscitation of 230 Vietnamese children with DSS. All the children survived, and there was no clear advantage to using any of the 4 fluids, but the longest recovery times occurred in the lactated Ringer's group. The most significant factor determining clinical response was the pulse pressure at presentation. A comparison of the colloid and crystalloid groups suggested benefits in children presenting with lower pulse pressures who received one of the colloids. Further large-scale studies, stratified for admission pulse pressure, are indicated. Pentastarch is a hydroxyethyl starch similar to hetastarch, but with a lower average molecular weight (264,000 versus 450,000) and fewer hydroxyethyl groups (molar substitution ratio = 0.45 versus 0.70). These characteristics result in enhanced enzymatic hydrolysis, faster renal elimination (initial intravascular half-life = 2.5 versus 25.5 hours), and less effect on coagulation. We report on a randomized clinical trial comparing the clinical efficacy and safety of 10% pentastarch (group P) for plasma volume expansion after cardiac operations with that of 5% serum albumin (group A). During the first 24 hours after arrival of the patient in the intensive care unit, colloid was infused to maintain a cardiac index of 2.0 L/m2 or more and a mean arterial pressure within 10% of the preinduction value. Group P (n = 50) received 1706 +/- 393 ml of colloid (mean +/- standard deviation) during this period, and group A (n = 44), 1794 +/- 341 ml (p = no significant difference). Hemodynamic responses to infusion were similar for both groups, although in group P a greater increase in both cardiac index (0.5 +/- 0.5 versus 0.3 +/- 0.5 L/min/m2 in group A, p less than 0.01) and left ventricular stroke work index (10.8 +/- 8.0 versus 5.8 +/- 6.0 gm-m/m2, p less than 0.01) was observed during infusion of the first 500 ml. There were no significant differences in any of the measured respiratory parameters (alveolar-arterial oxygen gradient, estimated shunt fraction, and effective pulmonary compliance). Hemodilution with colloid significantly reduced serum protein levels in group P by 24 hours postoperatively (4.0 +/- 0.6 versus 5.0 +/- 0.7 gm/dl in group A, p less than 0.05), although mean serum colloid osmotic pressure was similar (15.4 +/- 2.6 [P] versus 15.5 +/- 2.7 mmHg [A], p = no significant difference). There were no significant between-group differences in prothrombin time, activated partial thromboplastin time, platelet count, bleeding time, or coagulation factors (fibrinogen, V, VII, VIII, or IX) on postoperative days 1 and 7. Perioperative fluid balance, weight change, chest tube output, red blood, platelet, or fresh frozen plasma usage, reexploration for bleeding, and clinical outcome were also similar. These findings indicate that pentastarch is as safe and effective s 5% albumin for plasma volume expansion after cardiac operations with no apparent adverse effects on coagulation. If commercially available at a lower cost than albumin, it would appear to be a reasonable first choice for colloid therapy in this setting. All patients admitted to an Intensive Care Unit were randomised to receive all volume replacement fluid as either human albumin solution or a synthetic colloid. A total of 475 patients were admitted during the study period. Patients' age, sex, APACHE score and calculated risk of death were assessed on admission. Outcome was assessed as length of Intensive Care stay and mortality. There was no difference between the groups. Subgroups of patients with APACHE score greater than 10, calculated risk of death greater than 50% and length of stay greater than 5 days were also evaluated but not significant differences were found between treatment groups. The use of albumin rather than 3.5% polygeline for volume replacement in the Intensive Care Unit has no influence on outcome. Successful resuscitation of the injured may be achieved more rapidly and with less fluid using hypertonic crystalloid solutions than with isotonic solutions. This randomized, double-blind study compared 0.9% normal saline (NS) to 1.8% hypertonic saline (HS) in 20 postoperative coronary artery bypass patients suffering uniform injury. Study solutions were administered to maintain physiologic endpoints: heart rate, blood pressure, and pulmonary capillary wedge pressure. The groups were similar with respect to age, body surface area, operative procedure, intraoperative fluid status, and intraoperative and postoperative red cell transfusion requirements. HS patients required 30% less fluid than NS patients and were in negative fluid balance during the study (-1,715 +/- 732 ml/24 hr, HS, vs. +266 +/- 825 ml/24 hr, NS; p less than 0.01). In contrast, NS patients were in positive fluid balance after 8 hours. Moreover, HS patients experienced less chest tube drainage than NS patients (981 +/- 88 ml, HS, vs. 1,700 +/- 285 ml, NS; p less than 0.01). Systemic and pulmonary hemodynamic measurements, oxygen delivery, oxygen consumption, and shunt fraction did not differ between the two groups. Serum sodium and osmolality increased in the HS group and peaked at 12 hours (145.4 +/- 1.4 mEq/L and 308.7 +/- 2.0 mOsm/kg, respectively) and correlated with the volume of HS infused (correlation coefficient = 0.81). No deaths occurred and no complication was attributed the hypertonicity of the solution. We conclude that 1.8% hypertonic saline is a safe alternative to isotonic crystalloid therapy in the fluid management of postoperative patients. Decreased third-space losses may occur with HS as suggested by the lower thoracic losses in the HS group; 1.8% NaCl may be the preferred solution in situations where excess free water administration is not desired, and where interstitial edema is detrimental to function and/or survival. To assess the efficacy of polyethylene glycol 3350 plus electrolytes (PEG + E; Movicol) as oral monotherapy in the treatment of faecal impaction in children, and to compare PEG + E with lactulose as maintenance therapy in a randomised trial.
                An initial open-label study of PEG + E in the inpatient treatment of faecal impaction (phase 1), followed by a randomised, double-blind comparison between PEG + E and lactulose for maintenance treatment of constipation over a 3-month period (phase 2) in children aged 2 to 11 years with a clinical diagnosis of faecal impaction.
                Disimpaction on PEG + E was achieved in 58 (92%) of 63 of children (89% of 2-4 year olds and 94% of 5-11 year olds) without additional interventions. A maximum dose of 4 sachets (for 2-4 year olds) or 6 sachets (for 5-11 year olds) was required; median time to disimpaction was 6 days (range, 3-7 days). Seven children (23%) reimpacted whilst taking lactulose, whereas no children reimpacted while taking PEG + E (P = 0.011). The total incidence rate of adverse events seen was higher in the lactulose group (83%) than in the PEG + E group (64%).
                PEG + E is safe and highly effective in the management of childhood constipation. It allows a single orally administered laxative to be used for disimpaction without recourse to invasive interventions. It is significantly more effective than lactulose as maintenance therapy, both in efficacy in treating constipation and efficacy in preventing the recurrence of faecal impaction. The effects of 4% plasma protein solution (group P), 6% dextran-70 (group D), and 5.5% oxypolygelatin (group G) on plasma volume and hemodynamics were compared with each other and with controls (group C) who received only maintenance infusion 20 h after coronary bypass surgery. After infusing 10 ml/kg of colloid at 1 g/min, the immediate increases in plasma volume were 6.1 ml/kg in group P, 8 ml/kg in group D, and 7.9 ml/kg in group G. After one hour, the corresponding increases were 4.2 ml/kg (group P), 8.2 ml/kg (group D), and 6.2 ml/kg (group G). The increases in pulmonary capillary wedge pressure and stroke index were greatest and most persistent in group D, second largest but shortest in duration in group G, and lowest in group P. In conclusion, the volume effects of these three colloid solutions in coronary bypass patients are comparable to those obtained in other elective surgical patients. Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300) To evaluate whether patients performing clean intermittent self-catheterization (CISC) for a short period preferred a prelubricated, hydrophilic, disposable polyvinyl chloride (PVC) catheter or a non-hydrophilic PVC catheter which could be used several times and that had to be lubricated by the patient.
                In a prospective cross-over study, 32 patients used each type of catheter for 3 weeks. After each 3-week period, the patients completed a questionnaire to assess comfort and preference, and urine specimens were obtained for culture.
                There was no significant difference between the groups in the frequency of CISC, discomfort when used, opinion on handling the catheters, preference toward one of the catheters, or of infection.
                Non-hydrophilic PVC catheters may be used safely and with no discomfort to the patient. In addition it may be possible for the healthcare system to save money, as the non-hydrophilic PVC catheters are much cheaper. To explore whether intravenous administration of routinely used crystalloid or colloid solutions differently affects the coagulation system, we investigated orthopaedic patients. Since crystalloid solutions might cause hypercoagulability, we here present our results on molecular markers of coagulation and fibrinolysis. Patients undergoing knee replacement surgery randomly received isovolemic amounts of lactated Ringer's solution, 6% hydroxyethyl starch 200/0.5 or 4% modified gelatine. Arterial blood samples for determination of specific molecular markers of activated coagulation (thrombin/antithrombin complex, D-dimer, prothrombin fragment F1 + 2), fibrinolysis (plasmin/alpha 2-antiplasmin complex, tissue plasminogen activator, plasminogen activator inhibitor-1), and concentrations of coagulation factor XIII were obtained at baseline, before tourniquet release, at the end of surgery and 2 h after operation. During the observation period, thrombin/antithrombin complex increased from 4.8 to 54.7 microg/l, D-dimer increased from 0.3 to 6.0 mg/ml, prothrombin fragment F1 + 2 increased from 1.7 to 5.9 nmol/l, tissue plasminogen activator decreased from 7.3 to 6.7 ng/ml, plasminogen activator inhibitor-1 increased from 68.4 to 71.0 ng/ml, plasmin/alpha 2-antiplasmin complex increased from 281.5 to 884 microg/l and factor XIII decreased from 89.0 to 58.5%. All parameters changed significantly but without any detectable difference in the response profile between the groups receiving different intravenous fluids. During knee replacement surgery a pronounced activation of the coagulation/fibrinolytic system was observed, regardless of whether patients received crystalloid or colloid fluids. Thus, these results cannot confirm the hypothesis that crystalloid fluids per se cause hypercoagulability in vivo. In 1986, a protocol comparing primary radiation therapy (RT) plus hydroxyurea (HU) to irradiation plus fluorouracil (5-FU) and cisplatin (CF) was activated by the Gynecologic Oncology Group (GOG) for the treatment of patients with locally advanced cervical carcinoma. The goals were to determine the superior chemoradiation regimen and to quantitate the relative toxicities.
                All patients had biopsy-proven invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix. Patients underwent standard clinical staging studies and their tumors were found to be International Federation of Gynaecology and Obstetrics stages IIB, III, or IVA. Negative cytologic washings and para-aortic lymph nodes were required for entry. Patients were randomized to receive either standard whole pelvic RT with concurrent 5-FU infusion and bolus CF or the same RT plus oral HU.
                Of 388 randomized patients, 368 were eligible; 177 were randomized to CF and 191 to HU. Adverse effects were predominantly hematologic or gastrointestinal in both regimens. Severe or life-threatening leukopenia was more common in the HU group (24%) than in the CF group (4%). The difference in progression-free survival (PFS) was statistically significant in favor of the CF group (P = .033). The sites of progression in the two treatment groups were not substantially different. Survival was significantly better for the patients randomized to CF (P = .018).
                This study demonstrates that for patients with locally advanced carcinoma of the cervix, the combination of 5-FU and CF with RT offers patients better PFS and overall survival than HU, and with manageable toxicity. We investigated long-term safety and efficacy of sealed capsule irrigation (SCI) during cataract surgery to prevent posterior capsule opacification (PCO).
                One eye of each of 17 patients (mean age: 70.1+/-9.7 years) who presented with bilateral cataracts was randomly chosen for SCI treatment. After phacoemulsification, the capsular bag was vacuum sealed with the PerfectCapsule device (Milvella) followed by SCI using distilled water for two minutes. No vacuum loss occurred during irrigation. Each patient's fellow eye served as a control. One hydrophilic acrylic intraocular lens model was implanted in all eyes. Five patients had to be excluded due to deep anterior chamber, small pupil or unilateral surgery. Follow-up examinations took place one day and one, three, six, 12 and 24 months after surgery. We evaluated safety parameters, anterior capsule (AC) overlapping and PCO.
                Postoperatively, mean best corrected visual acuity, pachymetry, endothelial cell count, intraocular pressure, AC overlapping and PCO showed no statistically significant difference between SCI and the control group (p>0.05, Wilcoxon test).
                SCI is a safe procedure and enables the specific pharmacological targeting of lens epithelial cells inside the capsular bag. Using distilled water, however, it is not possible to reduce PCO development significantly. Thus, alternative substances should be evaluated. Hypotension associated with spinal anesthesia for cesarean section is still a clinical problem. Colloid solutions seem preferable to crystalloid solutions for preloading. In most studies the overall rate of hypotension is reported. Few studies have, however, investigated the maternal and neonatal consequences of different levels of maternal hypotension.
                In this randomized, double-blinded study 110 patients presenting for elective cesarean section received either 1000 ml acetated Ringer's solution or 1000 ml 3% dextran 60 solution immediately before spinal anesthesia. The effect on overall hypotension, clinically significant hypotension (hypotension associated with maternal discomfort defined as nausea, retching/vomiting, dizziness or chest symptoms) and severe hypotension (systolic arterial pressure <80 mmHg) was studied.
                Dextran reduced the incidence of overall hypotension from 85 to 66% (P=0.03), reduced the incidence of clinically significant hypotension from 60 to 30% (P=0.002) and reduced the incidence of severe hypotension from 23 to 3.6% (P=0.004) compared to Ringer's solution. There were neither differences in neonatal outcome between treatment groups nor between neonates grouped after severity of maternal hypotension.
                Clinically significant hypotension seems to be a more suitable outcome variable than overall hypotension. The protective effect of the colloid solution increased with increased severity of hypotension. To examine the kinetics of volume loading with crystalloid and colloid infusions in critically ill patients after major surgery, using the pulse contour cardiac output (PiCCO) monitoring technique.
                This prospective, randomized, multicentre study of 11 ICUs involved 200 mixed postoperative hypovolaemic patients (50 patients per group) in Hungary. Patients received 10 ml kg of lactated Ringer's solution, succinylated gelatin 4% w/v, 130/0.4 hydroxyethyl starch 6% w/v (HES) or human albumin 5% w/v over 30 min. A complete haemodynamic profile was obtained at 30, 45, 60, 90 and 120 min after baseline. The peak haemodynamic effects, the 120 min changes compared with baseline, the area under the curve (AUC) for the haemodynamic parameters over 120 min and the haemodilution effect of the solutions were analysed. The primary outcome was to compare the AUCs and the secondary outcome was to evaluate the haemodynamic changes at 120 min.
                There were significant differences in the AUCs of the haemodynamic parameters between colloids and lactated Ringer's solution in the cardiac index and global end-diastolic volume index (GEDVI); human albumin vs. lactated Ringer's solution in stroke volume variation (SVV); and succinylated gelatin, HES vs. lactated Ringer's solution in the oxygen delivery index (DO2I). Colloid infusions (mainly HES and human albumin) at 120 min caused significant changes in central venous pressure, cardiac index, GEDVI, SVV, DO2I and central venous oxygen saturation compared with baseline. The haemodilution effect was significantly greater in colloids vs. lactated Ringer's solution.
                In postoperative hypovolaemic patients, lactated Ringer's solution can significantly improve haemodynamics at the end of volume loading, but this effect completely disappears at 120 min. Ten millilitres per kilogram of colloid bolus (especially HES) improved the haemodynamics at 120 min; however, this was by only 5-25% compared with baseline. The colloids caused significantly larger AUCs than lactated Ringer's solution, but only in the cardiac index, GEDVI and DO2I, plus human albumin in the SVV. Hemodilution in the acute phase of ischemic stroke is still controversial. Multicenter studies have failed to demonstrate any benefit. The present study focuses attention on analysis of circulation in stroke and on individual restabilization of circulation.
                The Amsterdam Stroke Study is a prospective, single-center, randomized clinical trial (n = 300). Normovolemic hemodilution is accomplished in a customized procedure by administration of 20% albumin plus crystalloids under hemodynamic and rheological monitoring in the acute phase of stroke. All patients receive general intensive care treatment and monitoring with a pulmonary artery catheter. This custom-tailored fluid therapy is guided on the basis of a target pulmonary capillary wedge pressure (12 +/- 3 mm Hg) and hematocrit (0.32 +/- 0.02). The control group receives only customized rehydration by infusion of crystalloids.
                We obtained significant (p less than 0.05) reduction in mortality at 3 months (from 27% to 16%) and an increase in independence at home (from 35% to 48%) after viscosity reduction by means of hemodilution with albumin in the subgroup with a hematocrit less than 0.45 (n = 201) (specific viscosity effect). We also obtained a significant (p less than 0.005) reduction in mortality at 3 months (from 27% to 8%) and an increase in independence (from 35% to 59%) after only rehydration with crystalloids in the subgroup with overt dehydration (hematocrit greater than or equal to 0.45; n = 51) as compared with the normal-hematocrit group without signs of dehydration (hematocrit less than 0.45; n = 103) (specific rehydration effect).
                This study may provide an explanation for the failures in former hemodilution trials and may re-establish proper hemodilution and rehydration as a valuable therapy in the acute phase of stroke, thus reducing mortality and improving independence after 3 months. To evaluate the use of 250 mL of a 7.5% sodium chloride solution, both with and without added dextran 70, for the prehospital resuscitation of hypotensive trauma patients.
                Double-blind randomized trial.
                Six trauma systems served by helicopter transport.
                Injured patients with systolic blood pressures less than 90 mm Hg at any time in the field or during helicopter transport.
                Infusion of study solution, in the field or during transport, followed by conventional isotonic solutions as needed. Solutions studied in four cohorts were as follows: (1) lactated Ringer's; (2) 7.5% sodium chloride (hypertonic saline); (3) 7.5% sodium chloride combined with 6% dextran 70; and (4) 7.5% sodium chloride combined with 12% dextran 70.
                Blood pressure response; survival to time of hospital discharge among the treatment groups; and survival compared with that predicted by norms from the Major Trauma Outcome Study (MTOS).
                The mean (+/- SD) change in systolic blood pressure on arrival in the emergency department was significantly higher in the hypertonic saline solution group than that in the lactated Ringer's solution group (34 +/- 46 vs 11 +/- 49 mm Hg, P < .03). Overall survival in the four treatment groups was 49%, 60%, 56%, and 45% (not statistically significant). Survival in the hypertonic saline solution group, however, was significantly higher than that predicted by the MTOS norms (60% vs 48%, P < .001). Survival to hospital discharge in patients with baseline Glasgow Coma Scale scores of 8 or less was correlated with treatment group (P < .05 by logistic regression and P < .01 by Cox proportional-hazards analysis; with survival in the hypertonic saline solution group [34%] vs lactated Ringer's solution group [12%]).
                Prehospital infusion of 250 mL of 7.5% sodium chloride is associated with an increase in blood pressure and an increase in survival to hospital discharge compared with survival predicted by the MTOS norms. Patients with low baseline Glasgow Coma Scale scores seem to benefit the most from 7.5% sodium chloride resuscitation. Hypertonic saline solution without added dextran 70 is as effective as the more expensive solutions that contain dextran 70. Cyclosporine has been effective in patients with steroid-refractory attacks of ulcerative colitis (UC). We investigated the effects of intravenous (IV) cyclosporine as single IV therapy (without glucocorticosteroids) for severe UC and compared these with the response to glucocorticosteroids.
                Patients with a severe attack of UC were randomized to treatment with IV cyclosporine, 4 mg x kg(-1) x day(-1), or with methylprednisolone, 40 mg/day, in a randomized, double-blind, controlled trial. After 8 days, patients who had a response received the same medication orally in combination with azathioprine. Patients were followed up clinically, endoscopically, and by scintigraphy. Renal function was assessed using urinary inulin clearances. Endpoints were clinical improvement, discharge from the hospital, and remission up to 12 months after intravenous therapy.
                Thirty patients were included. After 8 days, 8 of 15 patients (53%) who received methylprednisolone had a response to therapy vs. 9 of 14 (64%) receiving cyclosporine. In nonresponders, 3 of 7 methylprednisolone patients and 1 of 3 cyclosporine patients improved when both treatments were combined. No serious drug-related toxicity was observed with either treatment. At 12 months, 7 of 9 patients (78%) initially controlled with cyclosporine maintained their remission vs. 3 of 8 (37%) initially treated with methylprednisolone. No clinically significant decrease of renal function was observed.
                Cyclosporine monotherapy is an effective and safe alternative to glucocorticosteroids in patients with severe attacks of UC. To evaluate the safety and relative effectiveness of two diuretic protocols in the intensive care unit (ICU).
                Prospective, randomized comparative study.
                Thirty-three cardiac and medical ICU patients with pulmonary edema or fluid overload for which aggressive diuresis was intended.
                Enrolled patients were randomized to fluid management strategies combining fluid restriction and individually adjusted diuretic therapy by either continuous or bolus infusions of furosemide, titrated to achieve negative hourly fluid balance.
                Cumulative intake minus output (primary endpoint); change in serum creatinine, and length of ICU and hospital stay (secondary endpoints). Diuresis by either protocol was feasible, safe, and effective. The main outcome measures were not significantly different for either group managed with a standardized protocol.
                Protocol-guided diuretic management, with individualized titration of dosage to defined physiologic endpoints can be readily and safely implemented in the ICU. Both continuous and bolus diuretic regimens appear equally effective in achieving negative fluid balance. Larger studies with a randomized control arm are needed before these protocols can be recommended as routine practice. Chronicity and high therapeutic cost prompted this study to determine a cost-effective and efficacious regimen in treating narcotic-induced constipation. The efficacy of lactulose was compared with polyethylene glycol 3350/electrolyte solution for relief of methadone-induced constipation. This was a randomized, triple cross-over after control run-in (no treatment) study conducted at a methadone maintenance program in Baltimore, Maryland in 57 patients who are affected by opiate-induced constipation. The study was measured by self-reported frequencies, consistency, and ease of defecation during a 1 week run-in control period, followed by 3 treatment phases of 2 weeks each. Polyethylene glycol 3350/electrolyte solution and lactulose produced more "nonhard" stools than the placebo (P < 0.01) and control (P < 0.003). Polyethylene glycol 3350/electrolyte solution produced the loosest stool (P < 0.0001) compared with the control, whereas lactulose had the most adverse effects. There were no significant differences in reducing hard stool formation in either experimental group, but both were better than having nothing or just the placebo. Polyethylene glycol/electrolyte solution resulted in the loosest (diarrheal) stool. It is also likely that polyethylene glycol/electrolyte solution is the most cost effective. Current methods of crystalloid preload administration prior to spinal anaesthesia for elective caesarean section are relatively ineffective in preventing hypotension. This study examined the relevance of the timing of the fluid administered. Fifty women were randomly allocated to receive either 20 ml x kg(-1) of crystalloid solution during 20 minutes prior to induction of spinal anaesthesia (preload), or an equivalent volume by rapid infusion immediately after induction (coload). Significantly more patients in the coload group did not require vasopressor therapy pre-delivery (P=0.047). The coload group required a lower median dose (P=0.03) and a lower median number (P=0.04) of ephedrine doses for the treatment of maternal hypotension pre-delivery. There was no between-group difference in either the total cumulative dose, or in the total number of doses of ephedrine. Neonatal outcomes among the two groups were similar. Rapid crystalloid administration after, rather than over 20 minutes before the induction of spinal anaesthesia for elective caesarean section, may be advantageous in terms of managing maternal blood pressure prior to delivery. Twenty-three patients aged 20-58 years in a serious state of shock and suffering from major pelvic and femoral fractures sustained in traffic accidents were studied. As initial fluid management, either dextran 70 (1000-1500 ml) together with Ringer's acetate solution (2000-3000 ml), or Ringer's acetate alone (5000-8000 ml), was administered on a random basis. Thus, 12 patients received dextran and 11 patients crystalloid treatment to counteract shock. Both groups were given whole blood. The resuscitation time--i.e. the interval from the start of fluid therapy until a stable circulatory condition was achieved--was significantly shorter (P less than 0.001) in the dextran group (108 +/- 18 min; mean +/- S.D.) than in the Ringer group (170 +/- 43 min). During the post-resuscitative observation period of 6 days the dextran patients were given 500 ml of dextran daily, while the Ringer group did not receive any colloidal solution. To maintain a stable circulation and a urinary output above 50 ml/h the Ringer patients required significantly more (P less than 0.001) crystalloid solution (910 +/- 300 ml) daily than the dextran patients (460 +/- 400 ml). The frequency of adult respiratory distress syndrome (ARDS) was significantly lower (P less than 0.05) in the dextran group (0 of 12) than in the Ringer group (4 of 11). Thus, in the initial treatment of traumatic-haemorrhagic shock and in the post-resuscitative period dextran 70 would seem of advantage over Ringer's acetate both in shortening the shock period and in reducing the frequency of adult respiratory distress syndrome. The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids.
                In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points.
                The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate.
                The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.)
                2008 Massachusetts Medical Society We prospectively studied the safety of replacing intravenous delivery systems, including those used in total parenteral nutrition, at 72- compared with 48-hour intervals in 487 patients. Although the prevalence of contamination of intravenous fluid was higher in administration sets replaced at 72-hour intervals (10/664, 1.5%) than in sets replaced every 48 hours (6/710, 0.8%), the difference is not statistically significant. Contamination in both groups was almost exclusively with small numbers of coagulase-negative staphylococci (range, 1 to 27 colony-forming units/mL); no contaminated infusion was associated with clinical signs of sepsis or concordant bacteremia. Contaminants were recovered less frequently from peripheral venous infusions (0.6%) than from infusions used for central venous access or hemodynamic monitoring (1.5%) or total parenteral nutrition (3.6%); infusions in an intensive care unit were more frequently contaminated (2.5%) than infusions on medical and surgical wards (0.9%). These data indicate that extrinsic contamination of intravenous fluid is a rare cause of endemic nosocomial septicemia, and for most infusions it is unnecessary to routinely replace delivery systems more frequently than every 72 hours. The effect of Ringer's Lactate (RL) and a colloid containing salt solution Plasmanate (PL) on extravascular lung water (EVLW) during aortic surgery was evaluated in a prospective study of 18 patients. Measured blood loss was replaced with packed red blood cells. In addition to red blood cell replacement, either RL or PL was infused (1) to maintain the cardiac output (CO) equal to or greater than the preoperative value, (2) to maintain the pulmonary capillary wedge pressure (PCWP) plus or minus 2 mmHg of preoperative values, and (3) to keep the urinary output greater than or equal to 30 cc/hr. Cardiac output, EVLW, PCWP, serum colloid osmotic pressure (COP), and intrapulmonary shunt fraction (Qs/Qt) were measured serially. All baseline values were similar between groups. The groups were well matched for age, associated disease, operating time, blood loss, and blood transfusions. During operation, the RL group required two times the rate of infusion of the PL group. Urine flow rates were similar on the day of surgery, but by postoperative days one and two, the PL group had approximately one-half of the urine flow rate compared to the RL group. Cardiac output and Qs/Qt increased in both groups. EVLW did not change after operation in either group, despite marked decrease in COP in the RL group. These data indicate that crystalloid resuscitation to physiologic endpoints does not increase extravascular lung water. Thus, manipulation of COP by PL was unnecessary in these patients. The purpose of the study was to examine the effects of hypooncotic 4% hydroxyethyl starch 120/0.7, 3% dextran 70, 5% albumin and hyperoncotic 6% hydroxyethyl starch 120/0.7 on the perioperative colloid osmotic pressure (COP), albumin and protein concentrations and fluid balance. The plasma substitutes were used with red cell concentrates to replace blood loss with equal volume in sixty major abdominal or urological surgeries. A special effort was made to keep replacements and losses at even volumes constantly and to avoid fluctuation of blood volume. The blood specimen were obtained before induction, after each 20% blood loss, at the end of the recovery room phase and on the three following postoperative mornings. There were significant differences in the peroperative and immediate postoperative COPs. However, these differences had vanished by the first postoperative morning. COP was preserved above 16 mmHg in all groups throughout the study. The identical peroperative albumin and protein concentrations of the synthetic colloid groups suggests that their volume effect was the same, regardless of the varying COP. During the observation period there were no significant differences among the groups concerning the diuresis and the fluid balances. We conclude, that the hypooncotic 4% HES 120 and 3% dextran 70 solutions provide the same clinical effect as 6% HES 120 solution. Consequently less colloid is needed, which allows the use of greater volumes of the dilute colloid solutions in replacement therapy. To compare the new hydroxyethyl starch HES 130/0.4 (Voluven) and the standard HES 200/0.5 (pentastarch) regarding effectiveness for plasma volume substitution and safety of large volumes in heart surgery.
                Fifty-nine patients scheduled for coronary artery bypass grafting were enrolled in a prospective, randomised, double-blind, parallel-group, multicentre, clinical, phase III study. Hydroxyethyl starch was used as the exclusive artificial colloid for acute normovolemic hemodilution, priming of the heart lung machine, and for intra- and postoperative plasma volume substitution from induction of anesthesia until 16 hr after the end of surgery. Efficacy was evaluated by comparing the amount of colloid infused, hemodynamics, and colloid osmotic pressure (COP). Safety endpoints were blood loss, the use of allogeneic blood products, coagulation variables, and adverse events.
                Effectiveness, as assessed by the total amount of infused HES volumes within the treatment period, was similar between HES 130/0.4 and HES 200/0.5 (2,550 mL +/- 561 mL vs 2,466 mL +/- 516 mL). Also, no differences were found for the use of other colloids (pasteurised plasma), hemodynamics, and COP In HES 130/0.4 patients, the postoperative increase of von-Willebrand factor (vWF) was higher (P < 0.01), blood loss was lower, and less packed red blood cells were transfused.
                Hydroxyethyl starch 130/0.4 is an effective plasma volume expander in heart surgery and may be used as the sole artificial colloid to cover the perioperative period. We found a reduced influence of HES 130/0.4 on the physiologic postoperative increase of vWF. We report the results of the first clinical study on the use of a hypertonic saline-dextran solution for the prehospital management of hypotensive victims of penetrating trauma. During a 4-month period, 48 trauma patients with penetrating injuries and a prehospital systolic blood pressure of 90 mm Hg or less were infused in-field with 250 ml of either a hypertonic saline-dextran solution or the crystalloid plasmalyte A. There were no complications associated with the infusion of the hypertonic saline-dextran solution, and execution of the protocol by paramedic personnel was both safe and uniformly successful. The potential impact of this solution on medical care and the results of this feasibility study justify the initiation of a larger prospective, randomized clinical trial on the efficacy of this solution in the prehospital setting. Hemodialysis patients in whom permanent vascular access cannot be achieved are dependent on a central venous catheter. In such patients, catheter-related infections are a common and serious complication. This study was a randomized clinical trial to determine if topical Polysporin Triple antibiotic ointment applied to the central venous catheter insertion site could reduce the incidence of catheter-related infections. A total of 169 patients receiving hemodialysis through a central venous catheter were randomized to receive Polysporin Triple or placebo using a double-blind study design. In the 6-mo study period, infections were observed in more patients in the placebo group than in the Polysporin Triple group (34 versus 12%; relative risk, 0.35; 95% CI, 0.18 to 0.68; P = 0.0013). The number of infections per 1000 catheter days (4.10 versus 1.02; P < 0.0001) and the number of bacteremias per 1000 catheter days (2.48 versus 0.63; P = 0.0004) were also greater in the placebo group. Within the 6-mo study period, there were 13 deaths in the placebo group as compared with 3 deaths in the Polysporin Triple group (P = 0.0041). When all available follow-up information was included, the difference in survival remained significant (19 versus 9 deaths; P = 0.0027). Within the first 6 mo, infections were observed in 7 of the 13 placebo subjects who died (54%) as compared with no infections in the three Polysporin Triple subjects who died. The prophylactic application of topical Polysporin Triple antibiotic ointment to the central venous catheter insertion site reduced the rate of infections and was associated with improved survival in hemodialysis patients. Polyethylene glycol (PEG) 3350 is a non-absorbable, non-metabolised osmotic agent used in lavage solutions for gut cleansing.
                To compare the efficacy of PEG and lactulose in chronic constipation.
                A total of 115 patients with chronic constipation entered a multicentre, randomised, comparative trial. They initially received two sachets containing either PEG (13 g/sachet) or lactulose (10 g/sachet) and were given an option to change the dose to one or three sachets/day, depending on response.
                Ninety nine patients completed the trial. After four weeks, patients in the PEG group (n=50) had a higher number of stools and a lower median daily score for straining at stool than patients in the lactulose group (n=49). Overall improvement was greater in the PEG group. Clinical tolerance was similar in the two groups, but flatus was less frequently reported in the PEG group. The mean number of liquid stools was higher in the PEG group but the difference was significant only for the first two weeks. There were no serious adverse events and no significant change in laboratory tests in either group. At the end of the study, the number of sachets used by the patients was 1.6 (0.7)/day in the PEG group and 2.1 (0.7)/day in the lactulose group. Sixty one patients completed a further two months open study of one to three sachets PEG daily; there was no loss of efficacy and no serious toxicity. Conclusion: Low dose PEG 3350 was more effective than lactulose and better tolerated. In a randomized clinical trial designed to evaluate the effect of diuresis on infants with hyaline membrane disease, seven infants were treated with furosemide (2 mg/kg intravenously) and five received 5% dextrose water in 0.225% sodium chloride (control group). Arterial blood gas analyses performed before and during the six hours after treatment showed no significant difference between control and treated infants. Urine output and urine sodium and calcium loss were significantly increased (P less than .05) in the infants receiving furosemide. The diuresis seemed to have no effect on left atrial size determined echocardiographically, whereas measurements of dynamic skinfold thickness suggested mobilization of subcutaneous water. One infant became seriously dehydrated and hypotensive secondary to a massive diuresis. We concluded that furosemide had a potent diuretic effect in infants with hyaline membrane disease but does not improve cardiorespiratory function acutely. This may be because of failure to mobilize pulmonary interstitial fluid in the time period tested. It may also be possible that the presence of pulmonary interstitial fluid does not play an important role in the impairment of gas exchange in the acute stage of hyaline membrane disease. The aim of this study was to show that 6% hydroxyethyl starch (HES) 130/0.4 achieves a better resuscitation of the microcirculation than normal saline solution (SS), during early goal-directed therapy (EGDT) in septic patients.
                Patients with severe sepsis were randomized for EGDT with 6% HES 130/0.4 (n = 9) or SS (n = 11). Sublingual microcirculation was evaluated by sidestream dark field imaging 24 hours after the beginning of EGDT.
                On admission, there were no differences in Sequential Organ Failure Assessment score, mean arterial pressure, lactate, or central venous oxygen saturation. After 24 hours, no difference arose in those parameters. Sublingual capillary density was similar in both groups (21 ± 8 versus 20 ± 3 vessels/mm(2)); but capillary microvascular flow index, percent of perfused capillaries, and perfused capillary density were higher in 6% HES 130/0.4 (2.5 ± 0.5 versus 1.6 ± 0.7, 84 ± 15 versus 53 ± 26%, and 19 ± 6 versus 11 ± 5 vessels/mm(2), respectively, P < .005).
                Fluid resuscitation with 6% HES 130/0.4 may have advantages over SS to improve sublingual microcirculation. A greater number of patients would be necessary to confirm these findings.
                Copyright © 2010 Elsevier Inc. All rights reserved. Fifty-eight patients who were to undergo aortic reconstruction were prospectively randomized into two groups to compare the effects of perioperative fluid replacement with isotonic and hypertonic crystalloid solutions. Blood loss was replaced with packed red blood cells, and additional fluid was given as either Ringer's lactate solution (RL, 130 mEq sodium/L, 274 mOsm/L) or a hypertonic balanced salt solution (HSL, 250 mEq sodium/L, 514 mOsm/L). Fluid was administered to maintain the cardiac filling pressure within 3 torr of the preoperative level and the cardiac output (CO) at or above the preoperative level. The groups were similar with respect to age, preexisting disease, duration of operation, and operative blood loss. During the operation, the RL group required 9.5 +/- 0.8 L of fluid, whereas the HSL group required 4.5 +/- 0.3 L (P less than 0.001). Pulmonary, cardiac, and renal functions were adequately maintained in both groups. There were no significant differences between the groups with regard to CO, urine output, or creatinine clearance during the operation and early postoperative period. Postoperatively, the intrapulmonary shunt was 20 +/- 1% in the RL group and it was 16 +/- 1% in the HSL group (P less than 0.05). The amount of sodium infused and the cumulative sodium balance at the completion of the study period were similar in both groups. Serum sodium and osmolarity were significantly greater in the HSL group (P less than 0.001), reaching a maximum of 151 +/- 1 mEq/L and 305 +/- 2 mOsm/L, respectively. Two patients in the HSL group had a persistent elevation in serum osmolarity (greater than 320 mOsm/L) during operation, for which they received RL for the balance of the resuscitation. There were no complications that could be attributed to the hypertonicity of the solution. HSL is effective for resuscitation of patients with extracellular fluid deficit and is safe provided that the serum sodium and osmolarity are monitored during periods of large volume administration. Adhesion-related readmissions are frequent sequelae to gynaecological surgery. Attempts to prevent adhesions by separating healing peritoneal surfaces include site-specific barriers and hydroflotation by instilled solutions. Rapid absorption limits the effectiveness of solutions such as Ringer's lactated saline (RLS). This pilot study assessed the safety, tolerability and preliminary effectiveness of a non-viscous, iso-osmolar solution of 4% icodextrin, an alpha-1,4 glucose polymer with prolonged intraperitoneal residence, in reducing adhesions after laparoscopic gynaecological surgery.
                Women aged > or = 18 years, requiring laparoscopic adnexal surgery (n = 62), were entered into a randomized, open-label, assessor-blinded, multicentre study to compare 4% icodextrin with RLS. Treatments were coded in blocks of four with equal randomization to each group, and pre-allocated to consecutively numbered patients. At least 100 ml per 30 min was used for intra-operative lavage, with 1 l instilled post-operatively. Per protocol analysis included all eligible patients (n = 53); reformation analysis required one or more baseline adhesion (n = 42). Incidence, extent and severity of post-operative adhesions were assessed at second-look laparoscopy after 6-12 weeks. Procedures were video-taped for third party, blinded assessment.
                Safety and tolerability (laboratory variables, adverse events, clinical follow-up) were good with no difference between treatments. A shift analysis of incidence-ranked adhesions (n = 53) showed apparent improvements in more patients with icodextrin than RLS (37 versus 15%; not significant). Adhesion score reduction (n = 42) was more frequent in icodextrin- than RLS-treated patients: incidence (52 versus 32%), extent (52 versus 47%), and severity (65 versus 37%). Despite greater baseline adhesions, median reformation was less after icodextrin (24%) than RLS (60%). The pilot study group sizes were not powered for statistical significance.
                In this preliminary study, 4% icodextrin lavage plus instillation was well tolerated and reduced adhesion formation and reformation following laparoscopic gynaecological surgery. A Phase III pivotal study is currently in progress. Cerebral blood flow (CBF) is reduced after subarachnoid hemorrhage (SAH), and symptomatic vasospasm is a major cause of morbidity and mortality. Volume expansion has been reported to increase CBF after SAH, but CBF values in hypervolemic (HV) and normovolemic (NV) subjects have never been directly compared.
                On the day after aneurysm clipping, we randomly assigned 82 patients to receive HV or NV fluid management until SAH day 14. In addition to 80 mL/h of isotonic crystalloid, 250 mL of 5% albumin solution was given every 2 hours to maintain normal (NV group, n=41) or elevated (HV group, n=41) cardiac filling pressures. CBF ((133)xenon clearance) was measured before randomization and approximately every 3 days thereafter (mean, 4.5 studies per patient).
                HV patients received significantly more fluid and had higher pulmonary artery diastolic and central venous pressures than NV patients, but there was no effect on net fluid balance or on blood volume measured on the third postoperative day. There was no difference in mean global CBF during the treatment period between HV and NV patients (P=0.55, random-effects model). Symptomatic vasospasm occurred in 20% of patients in each group and was associated with reduced minimum regional CBF values (P=0.04). However, there was also no difference in minimum regional CBF between the 2 treatment groups.
                HV therapy resulted in increased cardiac filling pressures and fluid intake but did not increase CBF or blood volume compared with NV therapy. Although careful fluid management to avoid hypovolemia may reduce the risk of delayed cerebral ischemia after SAH, prophylactic HV therapy is unlikely to confer an additional benefit. In previous comparative studies tacrolimus was superior to the standard formulation of ciclosporin in preventing acute rejection after renal transplantation. We have compared the microemulsion formulation of ciclosporin with tacrolimus in a multicentre randomised trial.
                The 6-month open study involved 560 patients in 50 European centres. 287 patients were randomly assigned tacrolimus and 273 ciclosporin microemulsion plus azathioprine and corticosteroids. The initial oral daily doses were 0.30 mg/kg for tacrolimus and 8-10 mg/kg for ciclosporin. The primary endpoint was the proportion of patients with biopsy-proven acute rejection and the time to this event.
                The two study groups were similar in terms of baseline characteristics. Three patients did not receive study treatment or did not undergo transplantation (one tacrolimus, two ciclosporin). The rate of biopsy-confirmed acute rejection was significantly lower with tacrolimus than with ciclosporin microemulsion (56 patients [19.6%] vs 101 [37.3%]; 17.7% difference [95% CI 10.3-25.1]; p<0.0001). Biopsy-confirmed corticosteroid-resistant rejection was also significantly lower with tacrolimus (27 [9.4%] vs 57 [21.0%]; 11.6% difference [5.7-17.5]; p<0.0001). Cross-over between therapies because of biopsy-proven rejection was judged necessary in one of 286 (0.3%) tacrolimus-group patients and 27 of 271 (10.0%) ciclosporin-group patients (p<0.0001). There were no significant differences in survival of patients or grafts or in renal function. The overall frequency of adverse events was similar in the two groups, though hypertension and hypercholesterolaemia were more common in the ciclosporin group and tremor and hypomagnesaemia were more frequent in the tacrolimus group.
                Tacrolimus was significantly more effective than ciclosporin microemulsion in preventing acute rejection after renal transplantation and had a superior cardiovascular-risk profile. Cardiovascular resuscitation of the severely injured patient in the field remains unsatisfactory because large volumes of intravenous fluid are needed to keep up with ongoing blood losses and because only small volumes of fluid can be given. In the first study reported here, small volumes (less than or equal to 12 mL/kg) of 3% NaCl were given to patients who were having surgery for severe injuries. The 3% NaCl restored blood pressure, pH, and urine output with approximately one half of the cumulative fluid requirement of patients who received isotonic fluids (p less than 0.05). In a second study, 7.5% NaCl/dextran 70, 250 mL, was given in a prospective, randomized, and double-blinded trial to injured patients in the field. Blood pressure in the hypertonic/hyperoncotic group increased 49 mmHg during transport (p less than 0.005); blood pressure in patients given lactated Ringer's solution increased 19 mmHg (NS). Survival favored the hypertonic/hyperoncotic group. The 7.5% NaCl/dextran 70 solution appears particularly promising for treatment of injured patients in the field. There is no generally accepted treatment for primary focal segmental glomerulosclerosis (FSGS). Steroids alone and steroids plus cyclophosphamide can be expected to induce a remission of the proteinuria in only 27% of patients. Probably the majority of FSGS patients will reach ESRD over the extended course of their disease. In addition to the work presented in this study, there have been many reports of the potential effectiveness of cyclosporine (CSA) on reducing the proteinuria of FSGS. This study was undertaken to test the efficacy and safety of a 6-month course of CSA in a double-blinded, prospectively randomized, placebo-controlled trial in children with corticosteroid-resistant FSGS. The potential inhibitory effect of hypercholesterolemia on the proteinuria-reducing actions of CSA was also assessed. Twenty-five patients with FSGS were randomized to receive either placebo or CSA for 6 months. Twelve of the 12 patients that received CSA experienced a diminution of their proteinuria as opposed to only two of the 12 placebo-treated patients. Proteinuria was significantly reduced from 151.7 +/- 162.4 mg/kg per 24 h at Week 0 to 36.9 +/- 42.3 at the end of the study in the group that received CSA (P < 0.05). There was no significant change in the proteinuria of the patients in the placebo group. A significant correlation between the percentage change of proteinuria over the 6 months of the study and the prestudy serum cholesterol levels (r = 0.79, P < 0.05) was seen in the CSA group. A partial correlation analysis controlling for the effects of serum cholesterol uncovered a significant relationship between average CSA level and proteinuria change (r = -0.76, P < 0.05). The fractional decline in GFR over the course of the study was not significantly different between the CSA and placebo-treated groups. In conclusion, CSA reduces proteinuria, increases serum albumin levels, and can be expected, therefore, to reduce the symptoms of nephrotic syndrome. Hypercholesterolemia antagonizes this effect of CSA. A prospective, randomized study of patients undergoing abdominal aortic surgery was undertaken to determine the effects of maintaining normal plasma colloid osmotic pressure (COPp) on postoperative renal function and excretion of water and electrolytes. Two groups of 13 patients were given whole blood transfusions to replace blood loss. One group (ALB) received 80 g albumin on the day of operation and 20 g albumin the following three days. The other group (NON-ALB) received no extra albumin. The glomerular filtration rate (GFR) did not change significantly from preoperative values on the first or fourth postoperative day in any of the groups. The differences between the groups were non-significant. COPp could not be correlated to either GFR or sodium or fluid balances. Postoperative sodium and water retention was found to depend on the amount of infused sodium. Unexplained fluid shifts to a "third space" did not occur. Administration of albumin in addition to quantitative blood loss replacement is unnecessary and expensive. Two clinical studies were carried out to investigate the efficacy and safety as well as the local and systemic availability of a hydroxyethylsalicyclate gel. A double blind, multicenter trial, involving 113 patients with nonarticular rheumatic back pain, revealed statistically significant relief of pain as compared with placebo. Local and systemic tolerance was excellent. An open study of bioavailability after local application in 16 patients showed a mean salicylate concentration of 0.93 +/- 0.5 microgram/ml in the synovial fluid and 0.40 +/- 0.23 microgram/ml in the synovial membrane, compared with 0.14 +/- 0.04 microgram/ml in the serum. Genetisinic acid was not detected, while OH-hippuric acid was detected only in the serum and synovial fluid. Hydroxyethyl starch or hetastarch (HES), a synthetic colloid for intravascular volume expansion, was compared with albumin after coronary artery operations in 30 patients (15 in each study group). Cardiac index, atrial pressures, heart rate, and systolic blood pressure were similar in both groups. There were no differences in cumulative urine output at 24 hours or in weight change during the first 7 postoperative days. Values for colloid osmotic pressure, as well as for this variable minus left atrial pressure, were lowest soon after bypass but returned to baseline within 4 hours, with no difference between groups in the first 24 hours or 7 days after operation. Coagulation variables were similar, but prothrombin and partial thromboplastin times were higher 12 hours postoperatively and fibrinogen level was lower 7 days postoperatively in the patients receiving HES. There was no clinical evidence of excessive bleeding, although cumulative chest drainage at 12 and 24 hours was slightly higher in the HES group (p = 0.09 and 0.08, respectively). We conclude that hetastarch is a safe and effective colloid to use following coronary operations. The objective of this study was to compare the antihypertensive efficacy and influence on renal function of perindopril and amlodipine in cyclosporine-treated renal allograft recipients with mild to moderate hypertension. We conducted a randomized, double-blind, double-dummy crossover trial in ambulatory patients. Four phases were conducted: 2 weeks on placebo, 8 weeks of maintenance (perindopril or amlodipine), and 2 weeks of washout between treatment periods. Ten hypertensive patients with stable renal allograft function transplanted more than 6 months previously and receiving cyclosporine as part of their immunosuppressive regimen were studied. The patients were allocated to perindopril (2 or 4 mg/d) and amlodipine (5 mg/d) in a random sequence. If office diastolic pressure was greater than or equal to 90 mm Hg after 4 weeks, the dosage was doubled and continued for another 4 weeks. The main outcome measures were office and 24-hour ambulatory blood pressure changes after 8 weeks of active treatment and treatment and time effect on glomerular filtration rate and effective renal plasma flow. Perindopril and amlodipine were equally effective in lowering office blood pressure and similarly efficacious for the 24-hour period of the day. Neither drug affected glomerular filtration rate or effective renal plasma flow. Both agents demonstrated equivalent capacity (time x treatment, P = .955) to reverse renal vascular resistance (amlodipine from 0.35 +/- 0.02 to 0.30 +/- 0.02 mm Hg/mL per minute per 1.73 m2; perindopril from 0.36 +/- 0.03 to 0.32 +/- 0.01) (time effect of all treatments together, P = .043).(ABSTRACT TRUNCATED AT 250 WORDS) To determine optimal fluid management after elective aortic surgery we compared postoperative administration of 5% dextrose Ringer's lactate solution (102 patients) with 5% dextrose half-normal saline solution (80 patients). For 72 hours after operation, intravenous fluids were titrated to maintain urine output between 50 and 100 ml/hr. The group receiving 5% dextrose Ringer's lactate required less intravenous volume per day (2005 +/- 138 ml [mean +/- standard error of the mean] vs. 2701 +/- 145 ml, p less than 0.05), gained less weight (0.8 +/- 0.2 kg vs. 3.2 +/- 0.2 kg, p less than 0.05), and sustained less hyponatremia (serum sodium reduction, 0.1 mEq/L vs. 4.5 mEq/L, p less than 0.05). The group receiving 5% dextrose Ringer's lactate exhibited consistently lower pulmonary capillary wedge pressure (7.3 +/- 1.0 mm Hg vs. 11.4 +/- 1.9 mm Hg) and required treatment for fluid overload in 9 of 102 instances compared with 30 of 80 instances with hypotonic saline solution (p less than 0.05). The patients receiving 5% dextrose Ringer's lactate maintained higher arterial PO2 at 40% forced inspiratory oxygen (PaO2, 83 +/- 3 torr vs. PaO2, 67 +/- 5 torr, p less than 0.05). Optimal fluid management was approached by the use of 5% dextrose Ringer's lactate solution postoperatively. The use of hypotonic saline solution after aortic surgery offered no advantage and predisposed the patient to volume overload. An examination was made of the possibility that 100 to 200 ml of intraperitoneal 32% dextran 70 and/or 0.5% hydrocortisone sodium succinate (randomized independently with similar volumes of Ringer's lactate solution) might help to lessen the postoperative formation of adhesions among patients undergoing surgical procedures for peritubal adhesions (n = 76), endometriosis (n = 27), or midtubal occlusion (n = 61). Patients in the first two groups who were given intraperitoneal corticosteroids were also given systemic steroids. Nonparametric comparison of median adhesion scores at operation and at subsequent laparoscopy showed that there was a poorer outcome with dextran than when dextran was not used in every subgroup except one (repeat salpingolysis after previous operation for adhesions), including first operations for adnexal adhesions (Mann-Whitney U = 200, m = 23, n = 26; p less than 0.05). The probability was small (p beta less than 0.002) that an important beneficial effect of dextran was overlooked. Systemic corticosteroids were associated with a consistent trend toward improved outcome, especially in patients who initially had few or no adhesions, such as those operated on for endometriosis (U = 2, m = 7, n = 4; p less than 0.025), but among patients with tubal resections and anastomoses with adnexal adhesions the use of intraperitoneal hydrocortisone alone was associated with a worse outcome (U = 15, m = 12, n = 8; p less than 0.02). Life-table analysis of the accumulating probability of pregnancy showed that no significant difference resulted from adjunct use in any group. The conclusion is that no empiric basis supports the use of intraperitoneal 32% dextran 70 or 0.5% hydrocortisone in the attempt to prevent peritoneal adhesions, but further investigations on the systemic administration of corticosteroids to decrease the formation of adhesions would be useful. Because granulocyte colony-stimulating factor (G-CSF) has anti-inflammatory and neuroprotective properties and is known to mobilize stem cells, it may be useful in the treatment of acute ischemic stroke. We sought to examine the feasibility, safety and efficacy of using G-CSF to treat acute stroke.
                We conducted a randomized, blinded controlled trial involving 10 patients with acute cerebral infarction (middle cerebral artery territory as documented by the admission MRI) who presented within 7 days of onset and whose scores on the National Institutes of Health Stroke Scale (NIHSS) were between 9 and 20. Patients were assigned to either G-CSF therapy or usual care. The G-CSF group (n = 7) received subcutaneous G-CSF injections (15 microg/kg per day) for 5 days. The primary outcome was percentage changes between baseline and 12-month follow-up in mean group scores on 4 clinical scales: the NIHSS, European Stroke Scale (ESS), ESS Motor Subscale (EMS) and Barthel Index (BI). We also assessed neurologic functioning using PET to measure cerebral uptake of fluorodeoxyglucose in the cortical areas surrounding the ischemic core.
                All of the patients completed the 5-day course of treatment, and none were lost to follow-up. No severe adverse effects were seen in patients receiving G-CSF. There was greater improvement in neurologic functioning between baseline and 12-month follow-up in the G-CSF group than in the control group (NIHSS: 59% change in the mean G-CSF group score v. 36% in the mean control group score, ESS: 33% v. 20%, EMS: 106% v. 58%, BI: 120% v. 60%). Although at 12 months there was no difference between the 2 groups in cerebral uptake of fluorodeoxyglucose in the ischemic core, uptake in the area surrounding the core was significantly improved in the G-CSF group compared with the control group. There was positive correlation between metabolic activity and EMS score following simple linear correlation analysis.
                Our preliminary evidence suggests that using G-CSF as therapy for acute stroke is safe and feasible and leads to improved neurologic outcomes. ABSTRACT: INTRODUCTION: Inadequate initial treatment and delayed hemodynamic stabilization (HDS) may be associated with increased risk of death in severe sepsis patients. METHODS: In order to compare the hemodynamic efficacy and safety of 6% HES 130/0.4 and NaCl 0.9% for HDS in patients with severe sepsis, we designed a prospective, multicenter, active-controlled, double-blind, randomized study in intensive care units. RESULTS: 174 out of 196 patients reached HDS (88 and 86 patients for HES and NaCl, respectively). Significantly less HES was used to reach HDS vs. NaCl (1,379 ±886 ml in the HES group and 1,709 ±1,164 ml in the NaCl group (mean difference = -331± 1,033, 95% CI -640 to -21, P = 0.0185). Time to reach HDS was 11.8 10.1 hours vs. 14.3 ±11.1 hours for HES and NaCl, respectively. Total quantity of study drug infused over four consecutive days, ICU and hospital LOS, and area under the curve of SOFA score were comparable. Acute renal failure occurred in 24 (24.5%) and 19 (20%) patients for HES and NaCl, respectively (P = 0.454). There was no difference between AKIN and RIFLE criteria among groups and no difference in mortality, coagulation, or pruritus up to 90 days after treatment initiation. CONCLUSION: Significantly less volume was required to achieve HDS for HES vs. NaCl in the initial phase of fluid resuscitation in severe sepsis patients without any difference for adverse events in both groups. CLINICALTRIALS.GOV: NCT00464204. Twenty-six consecutive patients in hypovolemic shock were randomized to fluid challenge with 5% albumin (A), 6% hetastarch (H), or 0.9% saline (S) solutions. Fluid challenge consisted of 250 ml of test fluid every 15 min until the pulmonary artery wedge pressure (WP) reached 15 mm Hg. Thereafter, WP was maintained at 15 mm Hg for an additional 24 h with infusions of the same test fluid. Vital signs, hemodynamic and respiratory variables, as well as arterial lactate and colloid osmotic pressure (COP) were monitored according to protocol. Chest x-rays were performed by standardized technique before fluid challenge and at 12 and 24 h of maintenance fluid therapy and were evaluated for evidence of pulmonary edema. Cardiac function and hemodynamic stability were restored by fluid challenge with A, H, and S. Two to 4 times the volume of S as A or H was required to achieve similar hemodynamic endpoints. COP was increased by fluid challenge with A or H but was markedly reduced by fluid challenge with S and throughout the 24-h maintenance period. Fluid challenge resulted in reductions in COP-WP gradient of 62% in the A, 43% in the H, and 125% in the S groups. Resuscitation with S resulted in a significantly higher incidence of pulmonary edema (87.5%) than did resuscitation with A (22%) or H (22%). Urine output was not different among the groups at any time during the study. We conclude that 6% H performs as well as 5% A as a resuscitative fluid and that resuscitation with either of these colloids is associated with a lower incidence of pulmonary edema than is resuscitation with 0.9% S. The efficacy of intravenous or intraosseous infusion of 250 ml of 7.5% NaCl and 6% dextran 60 (H/H) was compared with intravenous Ringer's lactate (RL) for the initial treatment of patients with hemorrhagic shock due to upper gastrointestinal bleeding. 49 patients were randomly assigned to receive either H/H (n = 26) or RL (n = 23). In the first 16 patients with H/H and in all RL patients, solutions were infused by the intravenous route, while the intraosseous route through sternal puncture was chosen for the last 10 H/H subjects. H/H patients were analyzed together since no differences were noticed between the routes of infusion. The H/H group also received 2.3 +/- 0.7 liters of intravenous crystalloid solutions in the first hour and 4.4 +/- 0.1 liters in the 24-hour period, while RL received 3.3 +/- 0.7 and 7.3 +/- 2.4 liters, respectively. Blood pressure (BP) increased during the first 15 min in the H/H group (from 61 +/- 17/30 +/- 12 to 85 +/- 30/48 +/- 14 mm Hg) and thereafter, while remaining unchanged in the RL group (from 75 +/- 18/40 +/- 12 to 75 +/- 17/40 +/- 14 mm Hg; p less than 0.05). The differences between groups were significant throughout 24 h. Urine output and improvement of the Glasgow Coma Score were also higher in H/H patients than in the control group (p less than 0.05). There were 5 deaths in RL group and 1 in the H/H group. Sternal of peripheral vein infusion of 250 ml of 7.5% NaCl/6% dextran 60 is an effective initial treatment of hemorrhagic shock. The influence of antihypertensive treatment on the long-term evolution of arterial pressure and renal function was studied in a prospective controlled trial conducted in renal transplant recipients treated by cyclosporine. Within six months after transplantation, patients were randomly allocated to treatment by the angiotensin-converting enzyme inhibitor, lisinopril (ACEI, alone or associated with frusemide; N = 14), or the calcium antagonist, nifedipine (CA, alone or associated with atenolol; N = 11). Glomerular filtration rate (TcDTPA clearance) and effective renal plasma flow (hippuran clearance) as well as 24-hour urinary excretion of electrolytes and albumin were estimated at about 1 and 2.5 years of follow-up. Before initiation of antihypertensive therapy, the two groups were similar with regards to mean arterial pressure (119 +/- 2 vs. 120 +/- 4 mm Hg), effective renal plasma flow (285 +/- 26 vs. 248 +/- 33 ml/min/1.73 m2) and glomerular filtration rate (59 +/- 4 vs. 61 +/- 8 ml/min/1.73 m2 in the ACEI and CA groups, respectively). Both ACEI and CA treatments were associated with no change in renal function, a similar change in mean arterial pressure (ACEI -18 +/- 3; CA -13 +/- 5 mm Hg) and identical trough blood levels of cyclosporine. Urinary albumin excretion did not change significantly in any groups. Of interest, only in the ACEI group did filtration fraction significantly decrease (from 0.22 +/- 0.01% to 0.19 +/- 0.01% at final studies). These results indicate that in cyclosporine-treated transplant recipients, a satisfactory control of hypertension is obtained by chronic ACEI, which is as effective on arterial pressure as a combination of CA and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS) To compare a solution of 3% dextran-60 (D60) in Ringer's lactate (RL) with RL alone as maintenance fluids for abdominal aortic surgery.
                Randomized control trial of 20 consecutive patients undergoing elective aortic reconstructive surgery.
                A surgical ICU in a university hospital.
                Consecutive patients, mean age 64 yr. Five patients had abdominal aneurysm, 12 had aortic obstruction disease, and three had aortic renal bypass surgery. These patients were followed for 1 month.
                Pulmonary artery occlusion pressure of at least 10 mm Hg and a urine output greater than 30 mL/h were used to guide the intraoperative fluid infusion rates, which were 36 and 104 mL/kg of D60 and RL, respectively (ratio 1:2.9).
                Body weight at 24 hr had increased more with RL (7.8 kg) than with D60 (3.2 kg) infusion (p less than .01), despite intraoperative urine volumes of 151 and 92 mg/kg with RL and D60, respectively. Total intravascular albumin decreased from 0.7 g/kg (1.4 to 0.7 g/kg) in both groups, corresponding to a plasma volume (PV) loss of 13 mg/kg without fluid infusions. A total intravascular dextran of 0.5 g/kg resulted in a PV expansion at 1 hr of 4.4 mL/kg above preoperative level, in sharp contrast to 7.0 mL/kg decrease in PV with RL. Of the intraoperative 3% D60 and RL infused, an estimated 51% D60 and 6% RL remained as PV expansion at 1 hr.
                A diluted colloid solution in Ringer's lactate is of significant value in maintaining intravascular volumes and hemodynamics during and after major operative procedures. The kind of fluid for correcting hypovolaemia is still a focus of debate. In a prospective, randomized, controlled and double-blind study in patients undergoing major abdominal surgery, a total balanced volume replacement strategy including a new balanced hydroxyethyl starch (HES) solution was compared with a conventional, non-balanced fluid regimen.
                In Group A (n = 15), a new balanced 6% HES 130/0.42 was given along with a balanced crystalloid solution; in Group B (n = 15), an unbalanced conventional HES 130/0.42 plus an unbalanced crystalloid (saline solution) were administered. Volume was given when mean arterial pressure (MAP) was <65 mmHg and central venous pressure (CVP) minus positive end-expiratoric pressure (PEEP) level was <10 mmHg. Haemodynamics, acid-base status, coagulation (thrombelastography (TEG)) and kidney function (including kidney-specific proteins, N-acetyl-beta-d-glucosaminidase (beta-NAG) and alpha-1-microglobulin) were measured after induction of anaesthesia, at the end of surgery, 5 and 24 h after surgery.
                Group A received 3533 +/- 1302 mL of HES and 5333 +/- 1063 mL of crystalloids, in Group B, 3866 +/- 1674 mL of HES and 5966 +/- 1202 mL of crystalloids were given. Haemodynamics, laboratory data, TEG data and kidney function were without significant differences between the groups. Cl- concentration and base excess (-5 +/- 2.4 mmol L-1 vs. 0.4 +/- 2.4 mmol L-1) were significantly higher in patients of Group B than of Group A.
                A complete balanced volume replacement strategy including a new balanced HES preparation resulted in significantly less derangement in acid-base status compared with a non-balanced volume replacement regimen. The new HES preparation showed no negative effects on coagulation and kidney function. The results of a controlled trial to ascertain the usefulness of plasma infusion for the treatment of hemolytic-uremic syndrome (HUS) are reported. Criteria for admission were (1) observation within 8 days from first symptoms, (2) dialysis treatment required, and (3) no special treatments and no more than 25 ml blood/kg previously received. Children were subdivided according to age (less than or more than 3 years) and then randomly assigned to treatment with plasma or symptomatic therapy. Thirty-two children ranging in age from 4 months to 6 years entered this study; 17 received plasma (P+ group) and 15 only symptomatic therapy (P- group). The mean follow-up period was 16 months in both groups. Surgical renal biopsy was performed 29 to 49 days after onset in 11 P+ and 11 P- children, and 33 histologic findings were semiquantitatively evaluated. No death occurred in either group. No differences were found in blood pressure, proteinuria, or hematuria at the end of the follow-up period; in no case were severe arteriolar lesions found. There were no significant differences for the scores of the individual histologic measurements; on electron microscopy, no vascular changes were observed in seven children of the P+ group, whereas in five of seven of the P- group, thickening of the lamina rara interna and arteriolar damage were present. The ability of plasma to stimulate prostacyclin (PGI2) production, measured as its stable derivative 6-keto-PGF1 alpha, was within the normal range for all patients. In our patients with predominant glomerular involvement who were treated in a very early phase of HUS, infusions of plasma did not significantly influence the short- and medium-term clinical outcome and were not effective in severe HUS when given later in the course of the disease. A longer follow-up is needed to ascertain whether the presence of endothelial damage, demonstrated by electron microscopy in children who were not given plasma, is of clinical relevance. Colloid infusions are often given to treat hypotension in preterm infants. The aim of this work was to assess whether it was the amount of protein or the volume of the colloid infused which accounted for the observed increase in blood pressure. Sixty preterm infants were randomised (20 in each group) to receive 5 ml/kg 20% albumin, 15 ml/kg fresh frozen plasma, or 15 ml/kg 4.5% albumin. All infusions were given at a rate of 5 ml/kg/hour in addition to maintenance fluids. The infants were randomised when hypotensive (systolic blood pressure less than 40 mm Hg for two hours). There was no significant difference in the blood pressure of the three groups before or one hour after beginning the infusion. The mean increase in blood pressure one hour after completing the infusion, however, was significantly lower in infants receiving 20% albumin: 9% compared with 17% in the group receiving 4.5% albumin, and 19% in the group receiving fresh frozen plasma. It is concluded that the volume infused rather than albumin load is important in producing a sustained increase in blood pressure. We tested hypertonic saline solution (HS) to determine its effectiveness in surgical procedures for prostatic hypertrophy. We randomly selected 40 patients undergoing elective transurethral resection of the prostate for either infusion of HS (3% NaCl) at 4ml·kg(-1)·min(-1) (HS group) or lactated Ringer's solution (LR) at 8 ml·kg(-1)·min(-1) (LR group). Anesthesiologists regulated the intraoperative infusion rate as needed to maintain blood pressure. There were no differences in systolic blood pressure, heart rate, central venous pressure, or arterial blood oxygenation between the two groups. In the HS group, plasma sodium, chloride, and osmolality, measured in the recovery room, were significantly increased; however, they returned to preanesthetic levels the day after surgery. In the LR group, in contrast, plasma sodium decreased significantly and this lower value persisted for 1 day. An osmolar gap exceeding 10mOsm·kg(-1) was observed in 2 patients in the HS group, but plasma sodium remained at normal values. However, in the 1 patient in the LR group whose osmolar gap exceeded 10mOsm·kg(-1), plasma sodium was 115 mEq·I(-1). HS, at a low dose, is useful in the intraoperative management of transurethral resection of the prostate. A prospective randomized trial was designed to establish whether parenteral antibiotic prophylaxis was as effective as oral antimicrobial bowel preparation in preventing sepsis after colorectal surgery. Patients scheduled for elective resection of colorectal cancer received metronidazole and kanamycin either orally in the preoperative phase or parenterally as a short-term perioperative prophylaxis. The former regimen resulted in reduction of the microbial concentrations in the bowel contents in the absence of therapeutic serum concentrations at the time of operation, whereas the latter achieved therapeutic intraoperative serum levels without altering the colonic microflora. 72 patients were studied. There was no significant difference in the occurrence of postoperative sepsis between the two groups (a total of 72 patients). These results differ from those obtained at the Birmingham General Hospital using the same protocol, in which postoperative sepsis was significantly more common in the group of patients having oral bowel preparation. This difference was most probably due to an overgrowth of kanamycin-resistant coliforms during the period of oral antibiotic preparation. The presence of resistant organisms did not, however, result in failure of systemic prophylaxis. The authors conclude that short-term parenteral application is the safer method of antibiotic prophylaxis in colorectal surgery and is to be preferred to oral antimicrobial bowel preparation. The prospective feasibility study was designed to determine whether treatment with antithrombin (AT) concentrates could be used for patients with severe preeclampsia to provide clinical efficacy without the full systemic antihypertensive drug. Twenty-nine severe preeclamptic patients (24 to 36 weeks of gestation, gestosis index [GI] >/= 6 points) were randomized to receive AT (1500 U/day) or not. AT was given intravenously once daily for 7 consecutive days. Twenty-four hours of continuous infusion of 5000 U/day of unfractionated heparin was given simultaneously in both groups. There were no statistical differences in the clinical profiles of the two groups. Maternal symptoms were evaluated from the difference of GI before and after treatment, and fetal findings were evaluated from the changes of the biophysical profile score. Improvement was significantly greater in the AT group for both the GI ( P = 0.046) and the biophysical profile score ( P = 0.022). The improvement of coagulation parameters was also evaluated. The improvement of plasmin-plasmin inhibitor complex (PPIC), D-dimer levels, and platelet counts was observed in the AT group compared with the non-AT group. The coagulation index as a composite coagulation test parameter showed a significantly improvement in the AT group. No adverse events related to AT were observed. Given that AT plus heparin was significantly better than treatment with heparin alone for improvement of both GI and biophysical profile of infant, it is suggested that therapy with AT alone might be effective enough for severe preeclampsia.
From this review, there is no evidence that one colloid solution is more effective or safe than any other, although the CIs were wide and do not exclude clinically significant differences between colloids. Larger trials of fluid therapy are needed if clinically significant differences in mortality are to be detected or excluded.