Colloid Fluid Resuscitation Research Articles

Expert consensus on the use of human serum albumin in critically ill patients.

Expert consensus on the use of human serum albumin in critically ill patients.

Adoption of rescue colloid during burn resuscitation decreases fluid administered and restores end-organ perfusion

IntroductionTraditionally, lactated Ringer’s solution (LR) has been utilized for the resuscitation of thermally injured patients via the Parkland or Brooke formulas. Both of these formulas include colloid supplementation after 24 h of resuscitation. Recently, the addition of albumin within the initial resuscitation has been reported to decrease fluid creep and hourly fluids given. Our institution has previously advocated for a crystalloid-driven resuscitation. Given reports of improved outcomes with albumin, we pragmatically adjusted these practices and present our findings for doing so. MethodsOur burn registry, consisting of prospectively collected patient data, was queried for those at least 18 years of age who, between July 2017 and December 2018, sustained a thermal injury and completed a formal resuscitation (24 h). At the attending physician’s discretion, rescue colloid was administered using 25% albumin for those failing to respond to traditional resuscitation (patients with sustained urine output of <0.5 mL/kg over 2–3 h, or unstable vital signs and ongoing fluid administration). We compared the total volume of the crystalloid-only and rescue colloid resuscitation fluids given to patients. We also examined the in/out fluid balances during resuscitation. Statistical analysis was performed using Stata software. ResultsA total of 91 patients with thermal injuries were included: the median age was 40 (IQR 31–57), 73% were male, and 30 patients received rescue albumin. The percentage of total body surface area burned (%TBSA) was greater in those who received rescue albumin (40.3% vs. 34%; p = 0.047). Despite a higher %TBSA in the albumin group, the total LR given during resuscitation was not significantly different between groups (15,914.43 mL vs. 11,828.71 mL; p = 0.129) even when normalized for TBSA and weight (ml LR/kg/%TBSA: 4.31 vs. 3.66; p = 0.129. The average in/out fluid ratio for the rescue group was higher than for the crystalloid group (0.83 ± 0.05 vs. 0.59 ± 0.11; p = 0.06) and returned to normal after colloid administration. ConclusionRescue albumin administration decreases the amount of fluid administered per %TBSA during resuscitation, and also increases end organ function as evidenced by increased urinary output. These effects occurred in patients who sustained larger burns and failed to respond to traditional crystalloid resuscitation. Our findings led us to modify our current protocol and a related prospective study of clinical outcomes.

Abstract 118: Resuscitative Transfusion With Hemoglobin Vesicles in the Management of Post-Partum Hemorrhage

Background: We developed a Hemoglobin vesicles (HbV), which are artificial substitute for Red blood cells (RBCs). Objective: To evaluate the efficacy of HbV for alternative treatment instead of RBCs transfusion in rabbits with hemorrhagic shock due to post-partum hemorrhage. Methods: New Zealand white rabbits at late gestation underwent uncontrolled hemorrhagic shock by transecting a right mid-artery in the myometrium, after cesarean section of right side uterus. Initially, in the simulated ordinal treatment of bleeding, rabbits received colloid fluids (Voluven®) through an femoral vein with equivalent volume of the bleeding every 5 minutes. Once blood loss achieved 100ml, animals subsequently faced on critical hemorrhagic situation, where mean arterial pressure (MAP) reduced to approximately 48mmHg. They were randomly divided into three isovolemic resuscitation regimens: continuing colloid fluid resuscitation (n=4); transfusion of autologous washed RBCs with plasma (n=4); HbV infusion combining 5% human serum albumin (n=4). After 60 minutes of bleeding, all animals underwent surgical control of bleeding and cesarean section of left side uterus. Results: At the point of critical hemorrhagic situation, Hb concentration reduced to 4.8 g/dl. At the end of resuscitation, HbV infusion regained MAP and restored Hb concentration as well as RBCs transfusion, besides colloid fluid resuscitation exaggerated the severe hemorrhagic shock as shown in the table. Conclusions: HbV treatment may be effective in the management of post-partum hemorrhagic shock.

Impact of Capnoperitoneum on Renal Perfusion and Urine Production in Infant and Adolescent Pigs: Crystalloid versus Colloid Fluid Resuscitation.

Infants are likely to develop anuria during laparoscopy which is uncommon in older patients. The reason for this susceptibility remains unknown. We compared the impact of CO2 pneumoperitoneum on renal perfusion and urine production in piglets compared with adolescent pigs. We furthermore investigated the effects of different resuscitation strategies. Male piglets (n = 21) were divided into four groups: (a) infant controls (n = 5), (b) infants with crystalloid restitution (n = 6), (c) infants with colloidal restitution (n = 5), and (d) adolescents with crystalloid restitution (n = 5). Animals were ventilated, the central vessels and ureters were cannulated, and the animals were subjected to a 3-hour, 10 mm Hg CO2 pneumoperitoneum followed by 2-hour resuscitation. Renal perfusion was assessed by fluorescent microspheres and the rate of urine flow was measured. Urine production significantly decreased after insufflation only in the infant crystalloid and adolescent group, but not in controls or infants treated with colloids. In the infant crystalloid group, urine production remained at levels below 20% of baseline throughout the experiment. In this group, the renal perfusion dropped significantly after the beginning of the capnoperitoneum and remained significantly reduced throughout the experiment. Our data indicates that capnoperitoneum impairs renal perfusion and urine production in infants. In moderate-pressure capnoperitoneum, this effect cannot be compensated by application of crystalloids but with colloids.

Prehospital Whole Blood in SOF: Current Use and Future Directions.

The US Joint Trauma System (JTS) recommends stored whole blood (SWB) as the preferred product for prehospital resuscitation of battlefield casualties in both their Tactical Combat Casualty Care (TCCC) guidelines and their clinical practice guidelines (CPGs). Clinical data from nearly 2 decades of war during Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) suggest that whole blood (WB) is safe, effective, and far superior to crystalloid and colloid resuscitation fluids. The JTS CPG for whole blood transfusion reflects the most recent clinical evidence but poses unique challenges for execution by Special Operations Forces (SOF) operating in austere environments. Given the limited shelf-life of 35 days, WB requires a constant steady pool of donors. Additionally, the cold-chain requirement for storage poses challenges for SOF on long missions without access to blood refrigerators. SOF operating in less-developed theaters face additional logistical challenges. To mitigate the challenges of WB delivery, US SOF have implemented various protocols to ensure optimal donor pool, awareness/education among medics and specialized equipment for tactical methods of blood-carry and delivery. In general, steps taken include the following: (1) Prior to deployment, soldiers are screened for blood type and titers in order to establish a large donor pool. Support soldiers have been found to be particularly beneficial donors as they typically are in closer proximity to the blood support detachment. (2) In units that operate in smaller teams, such as ODAs, medics are outfitted with "blood kits" to carry blood on missions for point of injury transfusion. In units with larger teams, LTOWB donors are identified on missions and deliver fresh WB in the event of casualties. (3) Medics receive a WB transfusion refresher tabletop exercise and review after action reviews from previous rotations. Additionally, prehospital WB delivery is a required component of scenario-based premission training. The expectation is that medics will administer WB on missions when tactically feasible. Using the prolonged field care framework (ruck, truck, house) as a template, medics now use different methods to store and transport the SWB depending on phase. Medic "truck" and "house" kits include the Dometic CFX™ powered coolers that run on AC, DC, or solar power and allow for constant temperature monitoring. When on foot, medics have been outfitted with tactical blood coolers including the Pelican Biomedical Medic 4™ or Combat Medical Blood Box™ along with a Belmont Buddy-Lite™ intravenous (IV) infusion warmer and IV administration kit with standard micron filter. Presently, SOF medics have the donor support, logistical framework, training, and equipment to deliver WB at the point of injury. However, widespread implementation will require expanded distribution and standardization of "blood kits." Additionally, SOF medical planners must put greater emphasis on education and the importance of WB over crystalloids or colloids-as many medics continue to carry only these products out of convenience. As SOF strive to establish tactics, techniques, and procedures (TTPs) and streamline prehospital WB delivery, we must constantly reassess and refine our procedures, incorporate the latest evidence and technology, and adapt to an evolving battlefield.

Acute abdominal compartment syndrome in a severely burned patient: Lack of colloid fluid availability in acute resuscitation may play a role

We report on a case in which a 27-year-old male patient sustained a significant burn injury requiring admission to the intensive care unit, with respiratory support and close haemodynamic monitoring. Owing to a lack of colloid resuscitation fluids, crystalloid fluids were used exclusively. The volume of fluid required to maintain an adequate urine output also resulted in fluid sequestration in other body compartments, eventually resulting in abdominal compartment syndrome. We believe this life-threatening complication could have been avoided had colloids been available

An Investigation Into the Effects of In Vitro Dilution With Different Colloid Resuscitation Fluids on Clot Microstructure Formation.

Balancing the beneficial effects of resuscitation fluids against their detrimental effect on hemostasis is an important clinical issue. We aim to compare the in vitro effects of 3 different colloid resuscitation fluids (4.5% albumin, hydroxyethyl starch [Voluven 6%], and gelatin [Geloplasma]) on clot microstructure formation using a novel viscoelastic technique, the gel point. This novel hemorheologic technique measures the biophysical properties of the clot and provides an assessment of clot microstructure from its viscoelastic properties. Importantly, in contrast to many assays in routine clinical use, the measurement is performed using unadulterated whole blood in a near-patient setting and provides rapid assessment of coagulation. We hypothesized that different colloids will have a lesser or greater detrimental effect on clot microstructure formation when compared against each other. Healthy volunteers were recruited into the study (n = 104), and a 20-mL sample of whole blood was obtained. Each volunteer was assigned to 1 of the 3 fluids, and the sample was diluted to 1 of 5 different dilutions (baseline, 10%, 20%, 40%, and 60%). The blood was tested using the gel point technique, which measures clot mechanical strength and quantifies clot microstructure (df) at the incipient stages of fibrin formation. df and clot mechanical strength decrease with progressive dilution for all 3 fluids. A significant reduction in df from baseline was recorded at dilutions of 20% for albumin (P < .0001), 40% for starch (P < .0001), and 60% for gelatin (P < .0001). We also observed significant differences, in terms of df, when comparing the different types of colloid (P < .0001). We found that albumin dilution produced the largest changes in clot microstructure, providing the lowest values of df (= 1.41 ± 0.061 at 60% dilution) compared with starch (1.52 ± 0.081) and gelatin (1.58 ± 0.063). We show that dilution with all 3 fluids has a significant effect on coagulation at even relatively low dilution volumes (20% and 40%). Furthermore, we quantify, using a novel viscoelastic technique, how the physiochemical properties of the 3 colloids exert individual changes on clot microstructure.

The crystalloid-colloid debate: Consequences of resuscitation fluid selection in veterinary critical care.

To provide a comprehensive review of the current literature in human and veterinary medicine evaluating the impact of resuscitation fluid choice on patient outcome and adverse effects. Prospective and retrospective studies, experimental models, and review articles in both human and veterinary medicine retrieved via PubMed. A series of recent, large, randomized controlled trials in critically ill human patients comparing crystalloid versus colloid driven fluid resuscitation algorithms have demonstrated no outcome benefit with the use of natural or synthetic colloids. Synthetic colloidal solutions are associated with an increased incidence of adverse effects including acute kidney injury, need for renal replacement therapy, and coagulopathies. Further, colloidal solutions demonstrate a larger volume of distribution in the setting of critical illness than hypothesized. These findings have created controversy regarding colloid fluid resuscitation in critically ill patients and challenge current resuscitation strategies. A thorough review of the most influential human data is provided. No veterinary clinical outcome data pertaining to fluid resuscitation choice currently exist. Veterinary data from experimental and small clinical trials evaluating the coagulopathic effects of hydroxyethyl starch solutions are described. Data pertaining to the use of natural colloids and albumin products in clinical veterinary patients are reviewed. In addition, data pertaining to the comparative intravascular volume expansion effectiveness of different fluid types in canine patients are reviewed. Clinical data from critically ill human patients have failed to demonstrate an outcome advantage associated with colloidal fluid resuscitation and indicate that hydroxyethyl starch solutions may be associated with significant adverse effects, including acute kidney injury, need for renal replacement therapy, coagulopathies, and pathologic tissue uptake. The ability to apply these findings to veterinary patients is unknown; however, similar pathophysiology may apply, and critical re-evaluation of resuscitation strategies is justified.

Effects of glycemic control on glucose utilization and mitochondrial respiration during resuscitated murine septic shock.

BackgroundThis study aims to test the hypothesis whether lowering glycemia improves mitochondrial function and thereby attenuates apoptotic cell death during resuscitated murine septic shock.MethodsImmediately and 6 h after cecal ligation and puncture (CLP), mice randomly received either vehicle or the anti-diabetic drug EMD008 (100 μg · g-1). At 15 h post CLP, mice were anesthetized, mechanically ventilated, instrumented and rendered normo- or hyperglycemic (target glycemia 100 ± 20 and 180 ± 50 mg · dL-1, respectively) by infusing stable, non-radioactive isotope-labeled 13C6-glucose. Target hemodynamics was achieved by colloid fluid resuscitation and continuous i.v. noradrenaline, and mechanical ventilation was titrated according to blood gases and pulmonary compliance measurements. Gluconeogenesis and glucose oxidation were derived from blood and expiratory glucose and 13CO2 isotope enrichments, respectively; mathematical modeling allowed analyzing isotope data for glucose uptake as a function of glycemia. Postmortem liver tissue was analyzed for HO-1, AMPK, caspase-3, and Bax (western blotting) expression as well as for mitochondrial respiratory activity (high-resolution respirometry).ResultsHyperglycemia lowered mitochondrial respiratory capacity; EMD008 treatment was associated with increased mitochondrial respiration. Hyperglycemia decreased AMPK phosphorylation, and EMD008 attenuated both this effect as well as the expression of activated caspase-3 and Bax. During hyperglycemia EMD008 increased HO-1 expression. During hyperglycemia, maximal mitochondrial oxidative phosphorylation rate was directly related to HO-1 expression, while it was unrelated to AMPK activation. According to the mathematical modeling, EMD008 increased the slope of glucose uptake plotted as a function of glycemia.ConclusionsDuring resuscitated, polymicrobial, murine septic shock, glycemic control either by reducing glucose infusion rates or EMD008 improved glucose uptake and thereby liver tissue mitochondrial respiratory activity. EMD008 effects were more pronounced during hyperglycemia and coincided with attenuated markers of apoptosis. The effects of glucose control were at least in part due to the up-regulation of HO-1 and activation of AMPK.Electronic supplementary materialThe online version of this article (doi:10.1186/2197-425X-2-19) contains supplementary material, which is available to authorized users.

Effects of limited fluid resuscitation on systemic inflammatory responses in rats with traumatic hemorrhagic shock: a comparison with unlimited fluid resuscitation

Objective To evaluate the effects of limited fluid resuscitation on systemic inflammatory responses in rats with traumatic hemorrhagic shock through comparing with unlimited fluid resuscitation.Methods Sixty pathogen-free male Sprague-Dawley rats,aged 2-3 months,weighing 250-290 g,were randomly divided into 6 groups (n =10 each) using a random number table:sham operation group (group S),no fluid resuscitation group (group NF),unlimited fluid resuscitation group (group ULF),limited crystalloid fluid resuscitation group (group LR),and limited colloid fluid resuscitation groups (group LSG and group LHES).Traumatic uncontrolled hemorrhagic shock was induced by withdrawal of blood from the femoral artery at 2.5 mL/100 g over a 20-minute period,followed by tail amputation at 10 min after the end of blood withdrawal.At 10 min after the end of blood withdrawal,fluid resuscitation was performed.Lactated Ringer's solution (ULF and LR groups),4 ％ succinylated gelatin (group LSG),or 6 ％ hydroxyethyl starch 130/0.4 (group LHES) was infused intravenously.The initial infusion rate was 2 ml · kg-1 · min-1.The target MAP was maintained at 50 mm Hg in rats with limited fluid resuscitation,while at 80 mm Hg in rats with unlimited fluid resuscitation.After 60 min of fluid resuscitation,bleeding in the tail was stopped by ligation and fluid infusion was replaced with blood resuscitation.After 60 min of blood resuscitation,180 main of observation was started.At 10 min after catheterization of the femoral artery and vein (T0),10 min after the end of blood withdrawal (T1),the end of fluid resuscitation (T2),the end of blood resuscitation (T3),and the end of observation (T4),arterial blood samples were collected to measure hematocrit (Hct)and concentrations of plasma tumor necrosis factor-alpha (TNF-α),interleukin (IL)-6,and IL-10.Blood samples were collected from the femoral artery at T2 for determination of the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) and activity of nuclear factor-kappaB (NF-κB) in monocytes.The amount of blood loss from the tail and volume of fluid infused were also recorded.Another 120 Sprague-Dawley rats were randomly divided into 6 groups (n =20 each) and resuscitation was performed according to the method previously described.The rats were observed for 72 h survival rate.Results Compared with group S,Hct was significantly decreased,the concentrations of plasma TNF-α,IL-6,and IL-10 and activity of NF-κB were increased,and the expression of TLR4,and MyD88 in monocytes was up-regulated in the other groups (P ＜ 0.05).Compared with group NF,the concentrations of plasma TNF-α and IL-6 and NF-κB activity were significantly increased,and the concentration of plasma IL-10 and Hct were decreased,and the expression of TLR4 and MyD88 in monocytes was up-regulated in ULF,LR and LSG groups,and the concentrations of plasma TNF-α and IL-6 were significantly increased,the concentration of plasma IL-10 and Hct were decreased in group LHES (P ＜ 0.05).Compared with group ULF,the concentrations of plasma TNF-α and IL-6 and NF-κB activity were significantly decreased,the concentration of plasma IL-10 and Hct were increased,the survival rate was higher,the expression of TLR4 and MyD88 in monocytes was down-regulated,and the amount of blood loss from the tail was decreased and the volume of fluid infused was reduced in LSG,LHES and LR groups (P ＜ 0.05).Compared with group LR,the concentrations of plasma TNF-α and IL-6 and NF-κB activity were significantly decreased and the expression of TLR4 and MyD88 in monocytes was down-regulated (P ＜ 0.05),and no significant change was found in the concentration of plasma IL-10 in group LHES (P ＞ 0.05),and the volume of fluid infused was reduced and the survival rate was increased (P ＜ 0.05),and no significant change was found in the amount of blood loss from the tail in LSG and LH-ES groups (P ＞ 0.05).Conclusion Compared with unlimited fluid resuscitation,limited fluid resuscitation exerts less effect on systemic inflammatory responses in rats with traumatic hemorrhagic shock,especially when resuscitation with 6％ hydroxyethyl starch 130/0.4 is performed,and inhibition of TLR4/NF-κB signaling pathway is involved in the mechanism. Key words: Resuscitation; Shock, hemorrhagic ; Systemic inflammatory response syndrome

Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study

IntroductionData are sparse as to whether obesity influences the risk of death in critically ill patients with septic shock. We sought to examine the possible impact of obesity, as assessed by body mass index (BMI), on hospital mortality in septic shock patients.MethodsWe performed a nested cohort study within a retrospective database of patients with septic shock conducted in 28 medical centers in Canada, United States and Saudi Arabia between 1996 and 2008. Patients were classified according to the World Health Organization criteria for BMI. Multivariate logistic regression analysis was performed to evaluate the association between obesity and hospital mortality.ResultsOf the 8,670 patients with septic shock, 2,882 (33.2%) had height and weight data recorded at ICU admission and constituted the study group. Obese patients were more likely to have skin and soft tissue infections and less likely to have pneumonia with predominantly Gram-positive microorganisms. Crystalloid and colloid resuscitation fluids in the first six hours were given at significantly lower volumes per kg in the obese and very obese patients compared to underweight and normal weight patients (for crystalloids: 55.0 ± 40.1 ml/kg for underweight, 43.2 ± 33.4 for normal BMI, 37.1 ± 30.8 for obese and 27.7 ± 22.0 for very obese). Antimicrobial doses per kg were also different among BMI groups. Crude analysis showed that obese and very obese patients had lower hospital mortality compared to normal weight patients (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.66 to 0.97 for obese and OR 0.61, 95% CI 0.44 to 0.85 for very obese patients). After adjusting for baseline characteristics and sepsis interventions, the association became non-significant (OR 0.80, 95% CI 0.62 to 1.02 for obese and OR 0.69, 95% CI 0.45 to 1.04 for very obese).ConclusionsThe obesity paradox (lower mortality in the obese) documented in other populations is also observed in septic shock. This may be related in part to differences in patient characteristics. However, the true paradox may lie in the variations in the sepsis interventions, such as the administration of resuscitation fluids and antimicrobial therapy. Considering the obesity epidemic and its impact on critical care, further studies are warranted to examine whether a weight-based approach to common therapeutic interventions in septic shock influences outcome.

Comparison of normal saline, hypertonic saline and hypertonic saline colloid resuscitation fluids in an infant animal model of hypovolemic shock

PurposeIncorrect resuscitation after hypovolemic shock is a major contributor to preventable pediatric death. Several studies have demonstrated that small volumes of hypertonic or hypertonic–hyperoncotic saline can be an effective initial resuscitation solution. However, there are no pediatric studies to recommend their use. The aim of this study is to determine if in an infant animal model of hemorrhagic shock, the use of hypertonic fluids, as opposed to isotonic crystalloids, would improve global hemodynamic and perfusion parameters. MethodsExperimental, randomized animal study including thirty-four 2-to-3-month-old piglets. 30min after controlled 30mLkg−1 bleed, pigs were randomized to receive either normal saline (NS) 30mLkg−1 (n=11), 3% hypertonic saline (HS) 15mLkg−1 (n=12), or 5% albumin plus 3% hypertonic saline (AHS) 15mLkg−1 (n=11). ResultsHigh baseline heart rate (HR) and low mean arterial pressure (MAP), cardiac index (CI), brain tissue oxygenation index (bTOI), and lactate were recorded 30min after volume withdrawal, with no significant differences between groups. Thirty minutes after volume replacement there were no significant differences between groups for HR (NS, 188±14; HS, 184±14; AHS, 151±14bpm); MAP (NS, 80±7; HS, 86±7; AHS, 87±7mmHg); CI (NS, 4.1±0.4; HS, 3.9±0.4; AHS, 5.1±0.4mLmin−1m−2); lactate (NS, 2.8±0.7; HS, 2.3±0.6; AHS, 2.4±0.6mmolL−1); bTOI (NS, 43.9±2.2; HS, 40.1±2.5; AHS, 46.1±2.3%). ConclusionsIn this model of hypovolemic shock, hypertonic fluids achieved similar end-points as twice the volume of NS. Animals treated with albumin plus hypertonic saline presented prolonged increase in blood volume parameters and recovery of the oxygen debt.

24 Comparison of Normal Saline, Hypertonic Saline and Hypertonic Colloid Resuscitation Fluids in An Infant Animal Model of Hemorrhagic Hypovolemic Shock

Background: Few studies have analyzed the effect of resuscitation fluid composition in infant animal models of hemorrhagic-hypovolemic shock. Our hypothesis was that hypertonic and hyperoncotic fluid will achieve goal-directed hemodynamic endpoints with less volume infusion than normal saline. Methods: Prospective, randomized study in 34 two month-old piglets (9.9±2kg). Following anaesthesia, paralysis and mechanical ventilation, hypovolemia was induced by controlled 30 ml/kg bleed. After 30 min, pigs were randomized to receive: Normal Saline (S0.9%) 30 ml/kg, n=11, Hypertonic 3% Saline (S3%) 15 ml/kg n=12, or Albumin 5% plus Hypertonic 3% Saline (A5%-S3%) 15 ml/kg, n=11. Hemodynamic (heart rate (HR), mean arterial pressure (MAP), cardiac index (CI)), brain tissue oxygenation by near infrared spectroscopy (bStO2) and tissue perfusion (arterial lactate and gastric pHi) parameters were compared by ANOVA. Results: 30 min. after bleeding, high baseline HR: 192±37, and low MAP 72±19 mmHg, CI 2.8±1L/min/m2, bStO2: 44±8%, gastric pHi 7.1±0.2 and lactate 3.4 ±2.3 mmol/L were recorded with non significant differences between groups. 30 min after infusion there were non significant differences between groups for HR (S0.9%: 188±14, S3%: 184±14, A5%-S3%: 151±14 bpm); MAP (S0.9%: 80±7, S3%: 86±7, A5%-S3%: 87±7 mmHg); CI (S0.9%: 4.9±0.5, S3%: 5.1±0.4, A5%-S3%: 5.3±0.4 ml/min/m2); lactate (S0.9%: 2.8±0.7, S3%: 2.3±0.6, A5%-S3%: 2.5±0.6mmol/l); bStO2 (S0.9%: 43.9±2.2, S3%: 40.1±2.5, A5%-S3%: 45.7±2.3 %); and pHi (S0.9%: 7.07±0.6, S3%: 7.25±0.5, A5%-S3%: 7.23±0.5). Conclusion: In this model of pediatric hypovolemic shock, both hypertonic (S3%) and hyperoncotic (A5%- S3%) fluids achieved similar hemodynamic endpoints, requiring half of the volume compared to normal saline.

The effects of commonly used resuscitation fluids on whole blood coagulation

Objectives: Evidence on the effect of crystalloid and colloid resuscitation fluids on coagulation is confusing, with contradictory results from previous studies. This study was performed to test the effect on...

Effects of crystalloid and colloid resuscitation on hemorrhage-induced vascular hyporesponsiveness to norepinephrine in the rat.

We have shown previously that hemorrhagic hypotension is associated with a progressive development of vascular hyporeactivity to norepinephrine (NE). The present study investigated whether select crystalloid or colloid resuscitation fluids would ameliorate this effect. Anesthetized male rats were hemorrhaged to and maintained at a mean arterial pressure (MAP) of 50 mm Hg for 60 minutes. Rats (n = 7 per group) were then resuscitated with lactated Ringer's (LR), 7.5% hypertonic saline (HS) for 1 hour followed by LR (HS-LR), Hespan, or Hextend to restore and maintain MAP to 70 mm Hg over 4 hours. Additional hemorrhaged groups were resuscitated with LR to the baseline MAP (LR-BL) or received no resuscitation. A sham hemorrhage group served as controls. The responses of MAP and the blood flow of the superior mesenteric, celiac, left renal, and left femoral arteries to NE (3 microg/kg administered intravenously) were measured at BL (prehemorrhage); at the end of the hypotensive period; and at 1, 2, and 4 hours after resuscitation. Hemorrhagic hypotension significantly (p < 0.01) reduced the NE-induced pressor response in MAP and significantly reduced the contractile responses (reflected by the reduction of blood flow after NE administration) of the four arteries to NE. Hespan and Hextend infusion improved the NE response of MAP and the contractile responses of the observed arteries to NE significantly better than LR, HS-LR, or LR-BL. The colloids improved the vascular contractile responses to NE in the superior mesenteric and left femoral arteries and the pressor response of MAP to NE, to 80% to 90% of their basal response level compared with 40% to 60% with the crystalloid fluids (p < 0.05). LR-BL infusion resulted in hemodilution, with no added benefit to vascular responsiveness. These data suggest that hypotensive resuscitation to 70 mm Hg with colloids was better than crystalloids in improving vascular responsiveness to the pressor effects of NE and required smaller volumes. Normotensive resuscitation with LR was not better than hypotensive resuscitation. Not all vasculatures improved equally after fluid resuscitation.

Effect of thoracic epidural anaesthesia on colonic blood flow

The effect of thoracic epidural block on splanchnic blood flow is unclear. It remains to be resolved if sympathetic block, increases or decreases regional splanchnic blood flow and whether regional splanchnic flow becomes dependent on cardiac output or perfusion pressure. A clear understanding of the regional haemodynamic consequences of an epidural block may modify practice with respect to epidural anaesthesia. Fifteen patients, who underwent anterior resection for rectal cancer, had invasive intraoperative monitoring of arterial pressure, central venous pressure, cardiac output, inferior mesenteric artery flow (Doppler flow probe), and colonic serosal red cell flux (laser Doppler probe), while an epidural block was established with local anaesthetic. In three consecutive time periods, arterial pressure was first allowed to fall (to a mean arterial pressure of 60 mm Hg), then treated with colloid fluid resuscitation and finally by vasopressors until the pre-epidural arterial pressure had been restored. On induction of epidural block, there was a reduction in mean colonic serosal red cell flux to 65% and inferior mesenteric artery flow to 80% (mean) of pre-epidural levels. There was a strong association between mean arterial pressure and both measured inferior mesenteric artery blood flow (P < 0.004) and colonic serosal red cell flux (P < 0.0001). Changes in cardiac output were poorly associated with either inferior mesenteric artery blood flow (P = 0.638) or colonic serosal red cell flux (P = 0.265). Inferior mesenteric artery blood flow and colonic serosal red cell flux were restored to pre-epidural levels after arterial pressure had been improved with a vasopressor. Once intraoperative epidural block has been established, colonic serosal red cell flux and inferior mesenteric artery flow are more closely associated with changes in mean arterial pressure than changes in cardiac output. The measured reduction in colonic flow does not respond to an increase in cardiac output with fluid resuscitation, but requires the use of a vasopressor to increase arterial pressure, before colonic blood flow is improved.

Crystalloid and colloid resuscitation of uncontrolled hemorrhagic shock following massive splenic injury.

Using a standardized massive splenic injury (MSI) model of uncontrolled hemorrhagic shock we studied the effect of vigorous crystalloid or colloid fluid resuscitation on the hemodynamic response, and survival in rats. The value of massive fluid infusion in uncontrolled hemorrhagic shock following intra-abdominal solid organ injury is still controversial. The effect of crystalloid and colloid infusion was studied following massive splenic injury. The animals were randomized into six groups: group 1 (n = 8) sham-operated, group 2 (n = 12) MSI untreated, group 3 (n = 10) MSI treated with 41.5 mL/kg Ringer's lactate (large-volume Ringer's lactate, LVRL), group 4 (n = 14) MSI treated with 5 mL/kg 7.5% NaCl (hypertonic saline, HTS), group 5 (n = 10) MSI treated with 7.5 mL/kg hydroxyethyl starch (HES-7.5), and group 6 (n = 11) MSI treated with 15 mL/kg hydroxyethyl starch (HES-15). Following MSI mean arterial pressure (MAP) in untreated group 2 decreased from 109.1 +/- 4.5 to 49.8 +/- 9.6 mmHg (P < 0.001) in 60 min. Mean survival time was 132.1 +/- 18.7 min, and total blood loss was 30.2 +/- 4.1% of blood volume. LVRL infusion resulted in an early rise in MAP from 59.7 +/- 7.3 to 90.0 +/- 11.3 mmHg (P < 0.01), which then rapidly dropped to 11.7 +/- 4.5 mmHg (P < 0.001) after 60 min. The mean survival time was 82.5 +/- 18.2 min (P < 0.01), and total blood loss was 53.7 +/- 2.9% (P < 0.01). Total blood loss following HTS infusion was 32.2 +/- 4.0% and survival time was 127.9 +/- 19.7 min. HES-7.5 infusion only moderately increased bleeding to 44.2 +/- 3.9% (P < 0.05), but mortality remained unchanged. HES-15 infusion resulted in an increase in blood loss to 47.8 +/- 7.1% (0.01), survival time dropped to 100.7 +/- 12.3 min (P < 0.05). Vigorous large volume infusion of Ringer's lactate or HES following MSI resulted in a significant increase in intra-abdominal bleeding and shortened survival time compared to untreated, small volume HTS, or HES-7.5-treated animals. The hemodynamic response to crystalloid or colloid infusion in blunt abdominal trauma is primarily dependent on the severity of injury and the rate of fluid resuscitation.

The capacity of different infusion fluids to lower the prooxidant activity of plasma iron: an important factor in resuscitation?

Prooxidant activity of non-protein-bound iron (NPBI) is an important contributor to reactive oxygen species-induced injury after the resuscitation of critically ill patients. Plasma NPBI occurs in critically ill adults, children, and newborn babies, who often require resuscitation. The ability of the resuscitation fluids to bind iron and lower the patients' NPBI levels in vitro has not previously been studied. In an in vitro model, highly iron-saturated cord blood plasma from 10 preterm and 10 term babies was mixed with FFP, pasteurized plasma protein solution, and 0.9-percent saline. Plasma from 10 healthy adult volunteers was used as a control. Before and after the mixing with any resuscitation fluid, NPBI levels and ceruloplasmin iron-oxidizing and transferrin iron-binding antioxidant capacities were measured. After the in vitro mixing with FFP, the incidence and concentration of NPBI were markedly decreased and the iron-binding antioxidant capacity was increased in the plasma of the preterm and term babies. Being mixed with pasteurized plasma protein solution and 0.9-percent saline did not influence the iron-binding antioxidant capacity of newborn babies' plasma. In the control plasma, results were not changed after the mixing with any resuscitation fluid. In every group, the iron-oxidizing antioxidant capacity was not changed after the mixing with any fluid. Iron-induced oxidative tissue damage may be influenced by resuscitation fluids. In the ongoing debate over the choice of crystalloid or colloid resuscitation fluids, the influence of each fluid on the patient's antioxidant capacity warrants more attention.

Crystalloid or colloid resuscitation of uncontrolled hemorrhagic shock after moderate splenic injury.

Using a standardized moderate splenic injury (MSI) model of uncontrolled hemorrhagic shock, we studied the effect of vigorous crystalloid or colloid fluid resuscitation on the hemodynamic response and survival time in rats. The animals were randomized into 6 groups: group 1 (n = 8) sham-operated, group 2 (n = 10) MSI untreated, group 3 (n = 10) MSI treated with 41.5 mL/kg Ringer's lactate (large-volume Ringer's lactate [LVRL]), group 4 (n = 10) MSI treated with 5 mL/kg 7.5% NaCl (hypertonic saline [HTS]), group 5 (n = 10) MSI treated with 7.5 mL/kg hydroxyethyl starch (HES-7.5), group 6 (n = 10) MSI treated with 15 mL/kg hydroxyethyl starch (HES-15). After MSI, mean arterial pressure (MAP) in group 2 decreased from 105.0+/-5.6 to 64.0+/-12.7 mmHg (P < 0.001) after 60 min. Mean survival time was 157.4+/-28.9 min, and total blood loss was 24.0+/-5.4% of blood volume. LVRL infusion resulted in an early rise in MAP from 75.2+/-8.7 to 96.7+/-9.0 mmHg (P < 0.01), which then rapidly dropped to 43.0+/-9.7 mmHg (P < 0.001) after 60 min. The mean survival time was 140.7+/-22.3 min, and total blood loss was 41.4+/-4.8% (P < 0.05). Total blood loss following HTS infusion was 24.7+/-3.7%, and mean survival time was 177.5+/-18.9 min. HES-7.5 infusion was followed by bleeding of 25.6+/-5.1%, and mean survival time was 181+/-16.1. HES-15 infusion resulted in an increase in blood loss to 48.2+/-7.3% (P < 0.05), and mean survival time of 133.0+/-27.7 min. Large-volume Ringer's lactate (LVRL) or hydroxyethyl starch (HES-15) infusion in uncontrolled hemorrhagic shock after moderate splenic injury resulted in a significant increase in intra-abdominal bleeding, but survival time remained unchanged compared with untreated, small-volume HTS-, or HES-7.5-treated animals. The hemodynamic response to large-volume crystalloid or colloid infusion was similar to moderate large-vessel injury.

An alternative pathway for preclinical research in fluid management.

Recent meta-analyses have created uncertainties regarding the appropriate clinical role of colloid resuscitation fluids in critically ill patients and prompted changes in fluid management practice. Such changes may not be justified in view of methodological limitations inherent in the meta-analyses. Further research is nevertheless needed to resolve the questions raised concerning the relationship between choice of resuscitation fluid and patient outcome. Animal studies can play an important part by reliably indicating whether particular fluids are likely to prove effective and safe in clinical trials. It is important to avoid costly large-scale clinical trials that fail to demonstrate the clinical utility of the tested therapy, as resources expended in failed trials raise overall development costs and thereby restrict the range of therapies meeting criteria of commercial feasibility. Promising therapies may thus not be pursued, even though an urgent clinical need may exist. An alternative pathway of preclinical research may be of value in avoiding some of the major clinical trial failures of recent years, particularly in the area of sepsis. This alternative pathway commences with the formulation of hypotheses by therapeutics developers. Independent preclinical investigators are challenged, by means of a competitive request for proposals, to test the hypotheses in rigorous randomized studies employing clinically relevant animal models. Promising proposals would then be selected for further development with the aid of peer review. The results of the randomized animal studies, along with other preclinical data, could also be evaluated using accepted principles of 'critical appraisal' commonly applied to clinical trial results. This critical appraisal might, where appropriate, include meta-analysis of animal study findings. This alternative preclinical pathway to new product evaluation should be completed before the commencement of large-scale clinical trials.