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Background Optimal infusion rate of colloids in patients with suspected hypovolemia is unknown, and the primary objective of the present study was to test if plasma volume expansion by 5% albumin is greater if fluid is administered slowly rather than rapidly. Methods Patients with signs of hypoperfusion after major abdominal surgery were randomized to intravenous infusion of 5% albumin at a dose of 10 ml/kg (ideal body weight) either rapidly (30 min) or slowly (180 min). Plasma volume was measured using radiolabeled albumin at baseline, at 30 min, and at 180 min after the start of infusion. Primary outcome was change in plasma volume from the start of infusion to 180 min after the start of infusion. Secondary outcomes included the change in the area under the plasma volume curve and transcapillary escape rate (TER) for albumin from 180 to 240 min after the start of albumin infusion. Results A total of 33 and 31 patients were included in the analysis in the slow and rapid groups, respectively. The change in plasma volume from the start of infusion to 180 min did not differ between the slow and rapid infusion groups (7.4 ± 2.6 vs. 6.5 ± 4.1 ml/kg; absolute difference, 0.9 ml/kg [95%CI, − 0.8 to 2.6], P  = 0.301). Change in the area under the plasma volume curve was smaller in the slow than in the rapid infusion group and was 866 ± 341 and 1226 ± 419 min ml/kg, respectively, P  < 0.001. TER for albumin did not differ and was 5.3 ± 3.1%/h and 5.4 ± 3%/h in the slow and in the rapid infusion groups, respectively, P  = 0.931. Conclusions This study does not support our hypothesis that a slow infusion of colloid results in a greater plasma volume expansion than a rapid infusion. Instead, our result of a smaller change in the area under the plasma volume curve indicates that a slow infusion results in a less efficient plasma volume expansion, but further studies are required to confirm this finding. A rapid infusion has no effect on vascular leak as measured after completion of the infusion. Trial registration EudraCT2013-004446-42 registered December 23, 2014.

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.

Background and objective The haemodynamics of crystalloid and colloid fluid loading may depend on underlying disease, i.e. sepsis versus non-sepsis. Design and setting A single-centre, single-blinded, randomized clinical trial was carried out on 24 critically ill sepsis and 24 non-sepsis patients with clinical hypovolaemia, assigned to loading with normal saline, gelatin 4%, hydroxyethyl starch 6% or albumin 5% in a 90-min (delta) central venous pressure (CVP)-guided fluid loading protocol. Transpulmonary thermodilution was done each 30 min, yielding, among others, global end-diastolic volume and cardiac indices (GEDVI, CI). Results Sepsis patients had hyperdynamic hypotension in spite of myocardial depression and dilatation, and greater inotropic/vasopressor requirements than non-sepsis patients. Independent of underlying disease, CVP and GEDVI increased more after colloid than saline loading ( P  < 0.018), so that CI increased by about 2% after saline and 12% after colloid loading ( P  = 0.029). The increase in preload-recruitable stroke work was also greater with colloids and did not differ among conditions. Conclusion Fluid loading with colloids results in a greater linear increase in cardiac filling, output and stroke work than does saline loading, in both septic and non-septic clinical hypovolaemia, in spite of myocardial depression and presumably increased vasopermeability potentially decreasing the effects of colloid fluid loading in the former.

Background: The choice of fluid is important in neurosurgical patients, who may be dehydrated due to the administration of diuretics in order to reduce cerebral edema. Normal saline, the infused fluid routinely used in neurosurgical patients, can cause hyperchloremic metabolic acidosis. A balanced crystalloid (BC) may help to maintain the metabolic status more favorably in these patients, without adversely affecting brain relaxation. Methods: We conducted a prospective, randomized controlled trial on patients undergoing elective craniotomy for supratentorial tumor resection under general anesthesia. 44 patients were randomly allocated into two groups of 22 each to receive either normal saline or BC (Plasmalyte) as the maintenance fluid, intra-operatively. The metabolic parameters and osmolality were measured at regular intervals. Brain relaxation score was assessed by the operating surgeon. The patients were monitored with serum neutrophil gelatinase-associated lipocalin (NGAL), blood urea and serum creatinine for assessing the degree of acute kidney injury. Results: The metabolic profile was better maintained with the BC. The brain relaxation score was comparable between the two groups. The postoperative NGAL, urea and creatinine values were significantly higher in the normal saline group compared to the BC group. Conclusion: The balanced crystalloid maintains metabolic status more favorably than normal saline in neurosurgical patients. Hyperchloremic metabolic acidosis, and the other problems which occur as a consequence of normal saline infusion may be circumvented by choosing a balanced crystalloid electrolyte solution. Neither of the crystalloids appeared to have any adverse effect on brain relaxation.

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.

Background Hyper- and hyponatremia are frequently observed in patients after subarachnoidal hemorrhage, and are potentially related to worse outcome. We hypothesized that the fluid regimen in these patients is associated with distinct changes in serum electrolytes, acid–base disturbances, and fluid balance. Methods Thirty-six consecutive patients with SAH were randomized double-blinded to either normal saline and hydroxyethyl starch dissolved in normal saline (Voluven ® ; saline ) or balanced crystalloid and colloid solutions (Ringerfundin ® and Tetraspan ® ; balanced , n  = 18, each) for 48 h. Laboratory samples and fluid balance were evaluated at baseline and at 24 and 48 h. Results Age [57 ± 13 years (mean ± SD; saline ) vs. 56 ± 12 years ( balanced )], SAPS II (38 ± 16 vs. 34 ± 17), Hunt and Hess [3 (1–4) (median, range) vs. 2 (1–4)], and Fischer scores [3.5 (1–4) vs. 3.5 (1–4)] were similar. Serum sodium, chloride, and osmolality increased in saline only ( p  ≤ 0.010, time–group interaction). More patients in saline had Cl >108 mmol/L [16 (89 %) vs. 8 (44 %); p  = 0.006], serum osmolality >300 mosmol/L [10 (56 %) vs. 2 (11 %); p  = 0.012], a base excess <−2 [12 (67 %) vs. 2 (11 %); p  = 0.001], and fluid balance >1,500 mL during the first 24 h [11 (61 %) vs. 5 (28 %); p  = 0.046]. Hyponatremia and hypo-osmolality were not more frequent in the balanced group. Conclusions Treatment with saline-based fluids resulted in a greater number of patients with hyperchloremia, hyperosmolality, and positive fluid balance >1,500 mL early after SAH, while administration of balanced solutions did not cause more frequent hyponatremia or hypo-osmolality. These results should be confirmed in larger studies.

Purpose To describe the current practices of volume expansion in French intensive care units (ICU). Methods In 19 ICUs, we prospectively observed the prescription and monitoring practices of volume expansion in consecutive adult patients with shock [sustained hypotension and/or need of vasopressor therapy, associated with at least tachycardia and/or sign (s) of hypoperfusion]. Patients were included at the time of prescription of the first fluid bolus (FB). Thereafter, all the FBs administered during the 96 h following shock onset were surveyed. An FB was defined as an intravenous bolus of at least 100 ml of a blood volume expander intended to rapidly improve the patient’s circulatory condition. Results We included 777 patients [age: 63 ± 15 years; female gender: 274 (35 %); simplified acute physiology score II: 55.9 ± 20.6; ICU length of stay: 6 days (interquartile range (IQR) 3–13); ICU mortality: 32.8 %] and surveyed 2,694 FBs. At enrolment mean arterial pressure was 63 mmHg (IQR 55–71). The most frequent triggers of FB were hypotension, low urine output, tachycardia, skin mottling and hyperlactataemia. Amount of fluid given at each FB was highly variable between centres. Crystalloids were used in 91 % (2,394/2,635) and synthetic colloids in 3.3 % (87/2,635) of FBs. Overall, clinicians used any kind of haemodynamic assessment (central venous pressure measurement, predictive indices of fluid responsiveness, echocardiography, cardiac output monitoring or a combination of these) in 23.6 % (635/2,694) of all FBs surveyed, with an important between-centre heterogeneity. Conclusions High between-centre variability characterised all the aspects of FB prescription and monitoring, but overall haemodynamic exploration to help guide and monitor FB was infrequent.

Background By tradition colloid solutions have been used to obtain fast circulatory stabilisation in shock, but high molecular weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis. Now lower molecular weight HES 130/0.4 is the preferred colloid in Scandinavian intensive care units (ICUs) and 1 st choice fluid for patients with severe sepsis. However, HES 130/0.4 is largely unstudied in patients with severe sepsis. Methods/Design The 6S trial will randomise 800 patients with severe sepsis in 30 Scandinavian ICUs to masked fluid resuscitation using either 6% HES 130/0.4 in Ringer's acetate or Ringer's acetate alone. The composite endpoint of 90-day mortality or end-stage kidney failure is the primary outcome measure. The secondary outcome measures are severe bleeding or allergic reactions, organ failure, acute kidney failure, days alive without renal replacement therapy or ventilator support and 28-day and 1/2- and one-year mortality. The sample size will allow the detection of a 10% absolute difference between the two groups in the composite endpoint with a power of 80%. Discussion The 6S trial will provide important safety and efficacy data on the use of HES 130/0.4 in patients with severe sepsis. The effects on mortality, dialysis-dependency, time on ventilator, bleeding and markers of resuscitation, metabolism, kidney failure, and coagulation will be assessed. Trial Registration ClinicalTrials.gov: NCT00962156

Background Since the advent of cardiopulmonary bypass, many efforts have been made to avoid the complications related with it. Any component of the pump participates in occurrence of these adverse events, one of which is the type of prime solution. In this study, we aimed to compare the effects of 6% hydroxyethyl starch 130/0.4 with a commonly used balanced electrolyte solution on postoperative outcomes following coronary bypass surgery. Methods Two hundred patients undergoing elective coronary bypass surgery were prospectively studied. The patients were randomized in to two groups. First group received a balanced electrolyte solution and the second group received 6% hydoxyethyl starch 130/0.4 as prime solution. The postoperative outcomes of the patients were studied. Results The mean age of the patients was 61.81 ± 10.12 in the crystalloid group whereas 61.52 ± 9.29 in the HES group. There were 77 male patients in crystalloid group and 74 in HES group. 6% hydroxyethyl starch 130/0.4 did not have any detrimental effects on renal and pulmonary functions. The intensive care unit stay and postoperative hospital length of stay were shorter in hydroxyethyl starch group (p < 0.05 for each). Hydroxyethyl starch did not increase postoperative blood loss, amount of blood and fresh frozen plasma used, but it decreased platelet concentrate requirement. It did not have any effect on occurrence of post-coronary bypass atrial fibrillation (p > 0.05). Conclusions 6% hydroxyethyl starch 130/0.4 when used as a prime solution did not adversely affect postoperative outcomes including renal functions and postoperative blood transfusion following coronary bypass surgery.

Background: 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. Methods: 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 ≥ 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·kg −1 ) were administered within goal directed care for the first 12 hr. Results: 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. Conclusion: 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.