Choice Of Resuscitation Fluid Research Articles

Can the choice of resuscitation fluid in a patient with traumatic brain injury affect the outcome?

Madam, Traumatic brain injury (TBI) refers to non-congenital, non-degenerative damage to the brain caused by an external mechanical force which can lead to permanent or temporary impairment of cognitive, psychosocial, and physical functions, accompanied by a reduced or altered state of consciousness.1 TBI is the most frequently occurring among common neurological disorders and accounts for a significant public health challenge.2 TBI has a high prevalence worldwide in adolescent (15 to 18 years) and elderly (>65 years) groups with a reported incidence of 1.7 million cases in the US alone.3 Pakistan also has a high prevalence of TBI with approximately one-third of its population being affected by it mainly due to the high incidence of road traffic accidents.4 Patients with TBI often present with clinical features of shock especially when the mechanism of injury is associated with high-energy trauma like road traffic accidents. In such cases, there is an imminent need for fluid resuscitation which becomes more important in under-served areas where immediate neurosurgical care is not available. It is widely known that crystalloids are superior to colloids for the resuscitation of the patient in such settings.5 The ringer lactate solution is usually preferred over normal saline for resuscitation in non-TBI settings because of lower mortality but the same is not true in TBI settings in which normal saline has been reported with significantly lower mortality. This difference can be attributed to the fact that ringer lactate being a balanced crystalloid, is hypo-osmotic, and thus can increase the intracranial pressure as well as the incidence of hyponatremia in patients with TBI.6 Therefore, in TBI, normal saline should be the fluid of choice for resuscitation instead of ringer lactate solution. The choice of fluid for resuscitation is of paramount importance in TBI, especially in a country like Pakistan where advanced healthcare facilities for neurosurgical care are not available in every city and village. Hence, many patients get referred to tertiary care centers from primary and secondary care centers after initial resuscitation for further management. In such cases, the correct choice of resuscitation fluid can significantly help in improving the odds of survival till patient’s arrival at higher care facility, and thereby help in decreasing the overall mortality associated with TBI.

A randomized-controlled trial comparing 20% albumin to plasmalyte in patients with cirrhosis and sepsis-induced hypotension [ALPS trial

The choice of resuscitation fluid in patients with cirrhosis and sepsis-induced hypotension is unclear. 5% albumin was superior to normal saline in the FRISC study. We compared the efficacy and safety of 20% albumin, which has greater oncotic properties, to plasmalyte in reversing sepsis-induced hypotension. Critically ill patients with cirrhosis underwent open-label randomization to receive either 20% albumin (0.5-1.0g/kg over 3 hours; n= 50) or plasmalyte (30ml/kg over 3 hours, n= 50). The primary endpoint of the study was the attainment of mean arterial pressure (MAP) above 65mmHg at 3 hours. Baseline characteristics were comparable in albumin and plasmalyte groups; arterial lactate (6.16±3.18mmol/L vs. 6.38±4.77mmol/L; p= 0.78), MAP (51.4±6.52mmHg vs. 49.9±4.45mmHg; p= 0.17) and SOFA score (10.8±2.96 vs. 11.1±4.2; p= 0.68), respectively. Most patients were alcoholics (39%) and had pneumonia (40%). In the intention-to-treat analysis, albumin was superior to plasmalyte in achieving the primary endpoint (62% vs. 22%; p <0.001). A faster decline in arterial lactate (p= 0.03), a reduced need for dialysis (48% vs. 62%; p= 0.16), and a longer time to initiation of dialysis (in hours) (68.13±47.79 vs. 99.7± 63.4; p= 0.06) were seen with albumin. However, the 28-day mortality rate was not different (58% vs. 62%, p= 0.57) and treatment had to be discontinued in 11 (22%) patients in the albumin group due to adverse effects compared to no discontinuations in the plasmalyte group. In patients with cirrhosis and sepsis-induced hypotension, 20% albumin leads to a faster improvement in hemodynamics and lactate clearance than plasmalyte, while 28-day survival was similar. However, patients on 20% albumin need to be closely monitored as it was more often associated with pulmonary complications. NCT02721238. The current randomized-controlled trial performed in critically ill patients with cirrhosis and sepsis-induced hypotension highlights that 20% albumin restores arterial pressure more quickly but causes more pulmonary complications than plasmalyte. The impact on renal functions was also modest. These effects did not result in improvement in survival at 28 days. Plasmalyte is safer and well-tolerated and can be considered for volume resuscitation in patients with cirrhosis and sepsis-induced hypotension.

From the Editor’s Desk…

From the Editor’s Desk…

Выбор инфузионно-трансфузионной среды для защиты эндотелиального гликокаликса

До недавнего времени теоретические преимущества одного типа жидкости для ресусцитации перед другим основывались на устаревшем в настоящее время понимании проницаемости сосудов. Коллоидные жидкости считались превосходящими кристаллоиды из-за их теоретически более высокого удержания во внутрисосудистом пространстве, но данные клинических исследований не подтвердили это и неубедительно продемонстрировали преимущества в отношении смертности пациентов или эффективности одного типа раствора перед другим. Эти наблюдения становятся понятными благодаря пересмотренному уравнению Старлинга, которое объясняет сходные свойства объемного расширения и образования отека из межклеточной жидкости у кристаллоидных и коллоидных растворов, когда повреждается эндотелиальный гликокаликс, а гидростатическое давление у критических пациентов падает. Принимаются во внимание также другие соображения, такие как эффекты накопления коллоидов в интерстициальном пространстве. Будущие исследования в области жидкостной реанимации получат пользу от обновленного понимания детерминант проницаемости сосудов, и, возможно, наиболее многообещающим является определение эндотелиального гликокаликса в качестве возможной терапевтической мишени. Инфузионно-трансфузионные среды различаются по своей способности защищать и восстанавливать эндотелиальный гликокаликс. Хотя свежезамороженная плазма была определена как наиболее эффективная субстанция, необходимы дальнейшие исследования для установления механизмов и определения того, улучшает ли репарация гликокаликса клинические результаты. Стратегия реанимации, которая защищает и восстанавливает эндотелиальный гликокаликс, может оказаться наиболее эффективной.

Resuscitation After Hemorrhagic Shock in the Microcirculation: Targeting Optimal Oxygen Delivery in the Design of Artificial Blood Substitutes.

Microcirculatory preservation is essential for patient recovery from hemorrhagic shock. In hemorrhagic shock, microcirculatory flow and pressure are greatly reduced, creating an oxygen debt that may eventually become irreversible. During shock, tissues become hypoxic, cellular respiration turns to anaerobic metabolism, and the microcirculation rapidly begins to fail. This condition requires immediate fluid resuscitation to promote tissue reperfusion. The choice of fluid for resuscitation is whole blood; however, this may not be readily available and, on a larger scale, may be globally insufficient. Thus, extensive research on viable alternatives to blood has been undertaken in an effort to develop a clinically deployable blood substitute. This has not, as of yet, achieved fruition, in part due to an incomplete understanding of the complexities of the function of blood in the microcirculation. Hemodynamic resuscitation is acknowledged to be contingent on a number of factors other than volume expansion. The circulation of whole blood is carefully regulated to optimize oxygen delivery to the tissues via shear stress modulation through blood viscosity, inherent oxygen-carrying capacity, cell-free layer variation, and myogenic response, among other variables. Although plasma expanders can address a number of these issues, hemoglobin-based oxygen carriers (HBOCs) introduce a method of replenishing the intrinsic oxygen-carrying capacity of blood. There continue to be a number of issues related to HBOCs, but recent advances in the next-generation HBOCs show promise in the preservation of microcirculatory function and limiting toxicities. The development of HBOCs is now focused on viscosity and the degree of microvascular shear stress achieved in order to optimize vasoactive and oxygen delivery responses by leveraging the restoration and maintenance of physiological responses to blood flow in the microcirculation. Blood substitutes with higher viscous properties tend to improve oxygen delivery compared to those with lower viscosities. This review details current concepts in blood substitutes, particularly as they relate to trauma/hemorrhagic shock, with a specific focus on their complex interactions in the microcirculation.

Resuscitation with Hydroxyethyl Starch Maintains Hemodynamic Coherence in Ovine Hemorrhagic Shock.

Fluid resuscitation in hemorrhagic shock aims to restore hemodynamics and repair altered microcirculation. Hemodynamic coherence is the concordant performance of macro- and microcirculation. The present study on fluid therapy in hemorrhagic shock hypothesized that the choice of fluid (0.9% sodium chloride [saline group] or balanced 6% hydroxyethyl starch 130/0.4 [hydroxyethyl starch group]) impacts on hemodynamic coherence. After instrumentation, 10 sheep were bled up to 30 ml/kg body weight of blood stopping at a mean arterial pressure of 30 mmHg to establish hemorrhagic shock. To reestablish baseline mean arterial pressure, they received either saline or hydroxyethyl starch (each n = 5). Hemodynamic coherence was assessed by comparison of changes in mean arterial pressure and both perfused vessel density and microvascular flow index. Bleeding of 23 ml/kg blood [21; 30] (median [25th; 75th percentile]) in the saline group and 24 ml/kg [22; 25] (P = 0.916) in the hydroxyethyl starch group led to hemorrhagic shock. Fluid resuscitation reestablished baseline mean arterial pressure in all sheep of the hydroxyethyl starch group and in one sheep of the saline group. In the saline group 4,980 ml [3,312; 5,700] and in the hydroxyethyl starch group 610 ml [489; 615] of fluid were needed (P = 0.009). In hemorrhagic shock perfused vessel density (saline from 100% to 83% [49; 86]; hydroxyethyl starch from 100% to 74% [61; 80]) and microvascular flow index (saline from 3.1 [2.5; 3.3] to 2.0 [1.6; 2.3]; hydroxyethyl starch from 2.9 [2.9; 3.1] to 2.5 [2.3; 2.7]) decreased in both groups. After resuscitation both variables improved in the hydroxyethyl starch group (perfused vessel density: 125% [120; 147]; microvascular flow index: 3.4 [3.2; 3.5]), whereas in the saline group perfused vessel density further decreased (64% [62; 79]) and microvascular flow index increased less than in the hydroxyethyl starch group (2.7 [2.4; 2.8]; both P < 0.001 for saline vs. hydroxyethyl starch). Resuscitation with hydroxyethyl starch maintained coherence in hemorrhagic shock. In contrast, saline only improved macro- but not microcirculation. Hemodynamic coherence might be influenced by the choice of resuscitation fluid.

Handbook of Sepsis

Editors Wiersinga and Seymour provide an aptly named Handbook of Sepsis: a compact and concise review of this common presentation. The Handbook, which can be mistaken for a novel on first glance, reads as such. It differs from the average critical care textbook with its casual inviting appearance, and yet provides a comprehensive review of multiple topics in sepsis care. The book is divided into 4 major sections, which comprise a total of 16 chapters by 36 international authors. The first of the 4 sections is an overview of sepsis, which includes a discussion of its historical and contemporary understanding, as well as a review on the epidemiological considerations. Long-recognized issues such as culture-negative sepsis are appropriately summarized. The second section focuses on important pathogenetic mechanisms, with topics including coagulopathy of sepsis, metabolic sequelae, and important biomarkers. These chapters are brief, appropriately focused, and provide an excellent overview of current understanding of these topics. The few included figures and tables were clear and complemented the text well. The majority of the book focuses on the third section: sepsis management. Chapters are devoted to topics including consensus guidelines, fluid therapy, vasopressor therapy, multiorgan failure, pathogen control, relevant antimicrobial therapy, and immunotherapy. Discussion of these management techniques includes a review of landmark studies that guide international standards of care, as well as a review of areas of academic equipoise (eg, choice of fluids for resuscitation). The final section elaborates on future directions in sepsis research and management. The authors provide the reader with a review of sepsis-specific trial design and research, considerations for low- or middle-income countries, and a brief chapter on future management trends to close (eg, precision medicine). The book has several strengths, such as a diverse authorship. These include internationally renowned thought leaders in sepsis such as Jean-Louis Vincent, Derek Angus, and Flavia Machado. Importantly, the authors have mostly contributed to chapters of which they have recognized content expertise, for example, Dr Derek Angus on trial design in sepsis research. Another strength is the balanced focus between knowledge that is immediately clinically relevant, and a basic science understanding of these principles that make the foundation of sepsis care. Ultimately, a scientific rationale for specific sepsis management therapy is center stage. This is truly where the Handbook shines: the science (from bench-to-bedside) presented is comprehensive without alienating nonmethods experts. It makes efforts to explain the science behind sepsis with chapters on clinical guidelines development as well as the previously mentioned trial designs section. While the book presents with multiple strengths, we believe that its title may not accurately depict its content. The Handbook reads very easily, however, unlike typical clinical handbooks, there is a relative deficiency of salient clinical pearls that may be applied at the bedside. These can be found embedded as nuggets of clinical nuance within the text, but having these summarized or immediately visible would be of value to the bedside clinician reading this text. Overall, this book provides the reader with the context on which sepsis care has been built, a review of current management, as well as a discussion of future trends. It would be a welcomed addition to a bookshelf of any trainee, health professional, or basic/clinical researcher who seek to immerse themselves into this complex and well-studied disease entity. It is concise and lends itself as an excellent, yet intimate, introduction into this vast topic area. Vatsal Trivedi, MDDepartment of Anesthesiology and Pain MedicineThe Ottawa HospitalUniversity of OttawaOttawa, Ontario, Canada Manoj M. Lalu, MD, PhDDepartment of Anesthesiology and Pain MedicineThe Ottawa HospitalUniversity of OttawaOttawa, Ontario, CanadaClinical Epidemiology and Regenerative Medicine ProgramsOttawa Hospital Research InstituteOttawa, Ontario, CanadaDepartment of Cellular and Molecular MedicineUniversity of OttawaOttawa, Ontario, Canada[email protected]; [email protected]

PP21 Rapid assessment of membrane osmotic pressure as a guide to resuscitation in the acutely shocked patient

BackgroundResuscitation of the shocked patient presents a dilemma for the prehospital resuscitation team. Selection of the appropriate type and quantity of resuscitation fluid is not supported by evidence based consensus and discussions such as the ‘crystalloid colloid debate’ have been prolonged and unhelpful. We are seeking a straightforward way of guiding resuscitation of shocked patients.The Prior Hypothesis suggests that capillary blood pressure and membrane osmotic pressure (MOP) must be equal and opposite to achieve fluid balance in the microcirculation. Membrane osmotic pressure is critically dependant on the pore size of small vessels – larger pores allowing the egress of large molecules from capillaries and therefore lowering capillary MOP. Our studies suggest that shocked patients fall into two groups: a ‘dry shock’ group with elevated MOP, and a ‘leaky shock’ group with a low MOP. The ability to identify these different groups has implications for treatment– both choice of resuscitation fluid, and the use of other vasoactive pharmacological agents which influence capillary pore size.MethodsConcurrent blood pressure and MOP were measured in 57 shocked patients on presentation to the Emergency Department. MOPs were measured using a process taking less than 5 min with a standalone osmometer requiring as little as 50 µl of serum.ResultsIn the patients tested two distinct patterns of abnormal MOP were distinguishable. 20 patients fell into the ‘leaky’ shock group (MOP 19–24 mmHg), 9 in the ‘dry’ shock group (MOP 27–30 mmHg) with a further 16 having MOP in the normal range (24–27 mmHg).ConclusionOur findings are consistent with the use of a rapid MOP test to categorise acutely presenting patients into ‘dry’ and ‘leaky’ shock depending on capillary pore size. Further work is required to test the utility of near patient MOP testing as a guide to effective therapy during emergency resuscitation.

Effect of Ringer\u2019s acetate in different doses on plasma volume in rat models of hypovolemia

BackgroundEven though crystalloids are the first choice for fluid resuscitation in hemodynamically unstable patients, their potency as plasma volume expanders in hypovolemia of different etiologies is largely unknown. The objective of the study was to investigate dose–response curves of a crystalloid in hypovolemia induced by either sepsis or hemorrhagic shock.ResultsRats were randomized to resuscitation with Ringers acetate at a dose 10, 30, 50, 75, or 100 ml/kg at 4 h after induction of sepsis by cecal ligation and puncture (CLP) or 2.5 h after a 30 ml/kg hemorrhage. Plasma volume (125I–albumin) was the primary outcome. Plasma volume decreased by about 11.8 (IQR 9.9–14.5) ml/kg relative baseline after CLP and increased dose-dependently by at most 5.8 (IQR 3.3–7.0) ml/kg in the 100 ml/kg group at 15 min after resuscitation. In the hemorrhage group, the plasma volume increased by at most 13.8 (IQR 7.1–15.0) ml/kg in 100 ml/kg group. Blood volumes at baseline, calculated using hematocrit and plasma volumes, were 72.4 (IQR 68.2–79.5) ml/kg in sepsis group and 71.1 (IQR 69.1–74.7) ml/kg in hemorrhage group. At 15 min after resuscitation with a dose of 100 ml/kg blood volumes increased to 54.8 (IQR 52.5–57.7) ml/kg and ; 49.6 (IQR 45.3–56.4) ml/kg, in the sepsis and hemorrhage groups, respectively. Plasma volume expansion as the percentage of dose at 15 min was 5.9 (IQR 2.5–8.8)% and 14.5 (IQR 12.1–20.0)% in the sepsis and hemorrhage groups, respectively. At 60 min, average plasma volume as the percentage of dose had decreased to 2.9 (IQR ([−2.9] − 8.3)% (P = 0.006) in the sepsis group whereas no change was detected in the hemorrhage group. A dose-dependent decrease in the plasma oncotic pressure, which was more marked in sepsis, was detected at 60 min after resuscitation.ConclusionsWe conclude that the efficacy of Ringers acetate as a plasma volume expander is context dependent and that plasma volume expansion is lower than previously realized across a wide range of doses. Ringers acetate decreases plasma oncotic pressure in sepsis, in part, by mechanisms other than dilution.

Choice of resuscitative fluids and mortality in emergency department patients with sepsis

ObjectiveBalanced resuscitative fluids (BF) have been associated with decreased incidence of hyperchloremic metabolic acidosis in sepsis. We hypothesized that higher proportions of BF during resuscitation would thus be associated with improved mortality in Emergency Department (ED) patients with sepsis. MethodsThis was a retrospective chart review of adult ED patients who presented with sepsis to a large, urban teaching hospital over one year. The choice of resuscitation fluid in the first 2days of hospitalization was defined as either normal saline (NS) or balanced fluids (BF; Lactated Ringer's or Isolyte). The primary study outcome was in-hospital mortality, which was analyzed with multivariable logistic regression based on the proportion of BF received during the initial ED resuscitation. ResultsOf 149 patients screened, 33 were excluded, leaving 115 for analysis, of whom 18 died (16% overall mortality). Sixty-one (53%) patients received BF and NS, 6 (5%) patients received BF exclusively, while 48 (42%) patients received NS only. The mean number of liters administered was 5.4, and the mean percentage of BF administered was 29%. In univariate analysis, a higher proportion of BF was associated with lower odds of mortality (OR 0.973 [95% CI 0.961–0.986], p=0.00003). This association held true in multivariable models controlling for comorbidities and admission lactate level. ConclusionsWe found that the proportion of BF during the initial ED resuscitation in septic patients was associated with a significant reduction in mortality. This association provides the necessary rationale for future randomized clinical trials of BF resuscitation in sepsis.

Choice of Fluids for Resuscitation of the Critically Ill: What Nurses Need to Know.

Fluid administration is one of the most universal interventions in the intensive care unit; however, there remains a lack of optimal fluid choice in clinical practice. With increasing evidence suggesting that the choice and dose of fluid may influence patient outcomes, it is important to have an understanding of the differences between the various fluid products and these potential effects in order for nurses to navigate the critically ill patient. This article reviews properties, adverse effects, and monitoring of commonly used colloid and crystalloid fluids, providing information that may aid in fluid selection in the intensive care unit.

Fluid resuscitation practice patterns in intensive care units of the USA: a cross-sectional survey of critical care physicians.

BackgroundFluid resuscitation is a cornerstone of intensive care treatment, yet there is a lack of agreement on how various types of fluids should be used in critically ill patients with different disease states. Therefore, our goal was to investigate the practice patterns of fluid utilization for resuscitation of adult patients in intensive care units (ICUs) within the USA.MethodsWe conducted a cross-sectional online survey of 502 physicians practicing in medical and surgical ICUs. Survey questions were designed to assess clinical decision-making processes for 3 types of patients who need volume expansion: (1) not bleeding and not septic, (2) bleeding but not septic, (3) requiring resuscitation for sepsis. First-choice fluid used in fluid boluses for these 3 patient types was requested from the respondents. Descriptive statistics were performed using a Kruskal-Wallis test to evaluate differences among the physician groups. Follow-up tests, including t tests, were conducted to evaluate differences between ICU types, hospital settings, and bolus volume.ResultsFluid resuscitation varied with respect to preferences for the factors to determine volume status and preferences for fluid types. The 3 most frequently preferred volume indicators were blood pressure, urine output, and central venous pressure. Regardless of the patient type, the most preferred fluid type was crystalloid, followed by 5 % albumin and then 6 % hydroxyethyl starches (HES) 450/0.70 and 6 % HES 600/0.75. Surprisingly, up to 10 % of physicians still chose HES as the first choice of fluid for resuscitation in sepsis. The clinical specialty and the practice setting of the treating physicians also influenced fluid choices.ConclusionsPractice patterns of fluid resuscitation varied in the USA, depending on patient characteristics, clinical specialties, and practice settings of the treating physicians.Electronic supplementary materialThe online version of this article (doi:10.1186/s13741-016-0035-2) contains supplementary material, which is available to authorized users.

Hypertonic saline in the traumatic hypovolemic shock: meta-analysis

BackgroundA wealth of evidence from animal experiments has indicated that hypertonic saline (HS) maybe a better choice for fluid resuscitation in traumatic hypovolemic shock in comparison with conventional isotonic saline. However, the results of several clinical trials raised controversies on the superiority of fluid resuscitation with HS. This meta-analysis was performed to better understand the efficacy of HS in patients with traumatic hypovolemic shock comparing with isotonic saline. Materials and methodsAccording to the search strategy, we searched the PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, which was completed on October 2013. After literature searching, two investigators independently performed the literature screening, assessment of quality of the included trials, and data extraction. Disagreements were resolved by consensus or by a third investigator if needed. The outcomes included mortality, blood pressure, fluid requirement, and serum sodium. ResultsSix randomized controlled trials were included in the meta-analysis. The pooled risk ratio for mortality at discharge was 0.96 (95% confidence interval [CI], 0.82–1.14), whereas the pooled mean difference for the change in systolic blood pressure from baseline and the level of serum sodium after infusion was 6.47 (95% CI, 1.31–11.63) and 7.94 (95% CI, 7.38–8.51), respectively. Current data were insufficient to evaluate the effect of HS on the fluid requirement for the resuscitation. ConclusionsThe present meta-analysis was unable to demonstrate a clinically important improvement in mortality after the HS administration. Moreover, we observed HS administration maybe accompanied with significant increase in blood pressure and serum sodium.

Pre-hospital and initial management of head injury patients: An update

Background:Most of the bad outcomes in patients with severe traumatic brain injury (TBI) are related to the presence of a high incidence of pre-hospital secondary brain insults. Therefore, knowledge of these variables and timely management of the disease at the pre-hospital period can significantly improve the outcome and decrease the mortality. The Brain Trauma Foundation guideline on “Prehospital Management” published in 2008 could provide the standardized protocols for the management of patients with TBI; however, this guideline has included the relevant papers up to 2006.Methods:A PubMed search for relevant clinical trials and reviews (from 1 January 2007 to 31 March 2013), which specifically discussed about the topic, was conducted.Results:Based on the evidence, majority of the management strategies comprise of rapid correction of hypoxemia and hypotension, the two most important predictors for mortality. However, there is still a need to define the goals for the management of hypotension and inclusion of newer difficult airway carts as well as proper monitoring devices for ensuring better intubation and ventilatory management. Isotonic saline should be used as the first choice for fluid resuscitation. The pre-hospital hypothermia has more adverse effects; therefore, this should be avoided.Conclusion:Most of the management trials published after 2007 have focused mainly on the treatment as well as the prevention strategies for secondary brain injury. The results of these trials would be certainly adopted by new standardized guidelines and therefore may have a substantial impact on the pre-hospital management in patients with TBI.

Is sodium chloride worth its salt?

The choice of fluid for resuscitation of the brain-injured patient remains controversial, and the 'ideal' resuscitation fluid has yet to be identified. Large volumes of hypotonic solutions must be avoided because of the risk of cerebral swelling and intracranial hypertension. Traditionally, 0.9% sodium chloride has been used in patients at risk of intracranial hypertension, but there is increasing recognition that 0.9% saline is not without its problems. Roquilly and colleagues show a reduction in the development of hyperchloremic acidosis in brain-injured patients given 'balanced' solutions for maintenance and resuscitation compared with 0.9% sodium chloride. In this commentary, we explore the idea that we should move away from 0.9% sodium chloride in favor of a more 'physiological' solution.

Intracranial pressure following resuscitation with albumin or saline in a cat model of meningitis*

To compare the intracranial pressure after resuscitation to normovolemia by using 20% albumin or normal saline in a cat model of meningitis. Prospective, randomized animal study. University hospital laboratory. Twenty adult, male cats. Meningitis was induced by intrathecal injection of Escherichia coli-derived lipopolysaccharide (0.8 × 10 units/kg). Four hours after the lipopolysaccharide injection, the animals were randomized to intravenous treatment with 0.4 mL/kg/hr of 20% albumin or 7.5 mL/kg/hr of 0.9% sodium chloride for 6 hrs (n = 7 per group). A control group receiving lipopolysaccharide but no fluid was also studied (n = 6). Effects on intracranial pressure, mean arterial pressure, plasma volume (I-albumin technique), plasma oncotic pressure, and brain metabolism via cerebral interstitial lactate/pyruvate ratio and glycerol and glucose levels (microdialysis technique) were evaluated. Plasma volume decreased by approximately 20% and intracranial pressure increased from 10 to approximately 20 mm Hg at 4 hrs after the lipopolysaccharide injection. Six hours later, plasma volume had returned to baseline in both fluid groups while there was a further reduction in the control group. Intracranial pressure was higher in the saline group than in the albumin and control groups and was 25.8 ± 2.8 mm Hg, 18.3 ± 0.6 mm Hg, and 20.4 ± 1.7 mm Hg, respectively. Plasma oncotic pressure was higher in the albumin group than in the saline and control groups. Mean arterial pressure and microdialysis data were within normal range and did not differ among the groups. The results showed that the choice of resuscitation fluid may influence intracranial pressure in meningitis. The lower intracranial pressure in the colloid group may be explained by a higher plasma oncotic pressure and less fluid distribution to the brain interstitium.

Choice of fluids for resuscitation in children with severe infection and shock: systematic review

Objective To systemically review the evidence from clinical trials comparing the use of crystalloids and colloids for fluid resuscitation in children with severe infection.Data sources Medline (1950-2008), PubMed, the Cochrane...

Phase III Trials Required to Resolve Clinical Equipoise over Optimal Fluid Management in Children with Severe Malaria

There is a consensus among paediatricians that outcome of children presenting with life-threatening infections, irrespective of the infecting pathogen, can be improved by timely recognition and prompt intervention to correct disordered physiology using simple approaches to resuscitation [1–3]. These approaches include the provision of oxygen and the correction of fluid, electrolyte, and glucose deficits [4,5]. Indeed, studies have shown that most of the recent gains in survival of children with severe infections have come through the application of this approach by non-specialists during the initial hours of management [6,7]. Correction of hypotension and volume depletion through fluid administration is a fundamental component of resuscitation in most critically ill children [8,9], but its role in severe malaria remains uncertain and thus represents one of the most important theoretical gaps in our understanding of supportive treatments in this condition. Many children with severe malaria have signs of cardiovascular compromise or compensated shock on presentation to hospital and a smaller proportion are hypotensive [10]. One of the major unresolved aspects of management is whether volume expansion should be undertaken in children displaying signs of compensated shock, as is recommended in other paediatric disorders. Intravascular volume depletion (hypovolaemic shock) results in impaired cardiovascular function and inadequate tissue and organ perfusion, and would usually be corrected rapidly. Simple dehydration, predominantly affecting the intracellular compartment, can be safely corrected gradually. The choice of the optimum fluid for resuscitation is also unclear. Colloidal solutions, although more costly, are less likely to precipitate cerebral and pulmonary oedema due to their oncotic properties. Recognising the importance of adequate fluid management to the outcome of the critically ill child, the group at Kilifi has conducted a staged series of studies over the last 15 years to address each of these questions. In a collaboration that included specialists in paediatric intensive care, neurology, and clinical trials, the group demonstrated the importance, prognostic implications [11], and clinical correlates of metabolic acidosis in children with severe malaria [12] and provided clear evidence of intravascular hypovolaemia by using standard methods for studying critical illness [13]. We have undertaken two randomised trials to assess the safety of and response to volume expansion, and to determine whether colloid replacement offers any advantage over crystalloid replacement [13,14]. We hypothesised that administration of colloids such as human albumin solution with volume expansion would help to retain fluid in the intravascular compartment and may also improve endothelial function. In each of these trials we observed that albumin administration was associated with a lower mortality than saline. Although this data suggested the need for a large clinical trial of albumin, in view of the cost of albumin we thought that cheaper synthetic colloids should be assessed before embarking on a phase III trial. The intention in the small phase II trial, recently published in PLoS Clinical Trials [15], was to provide sufficient physiological data on succinylated gelatin to inform the design of the next phase, rather than to establish statistical superiority of one colloid over the other. For this purpose the trial was most instructive. Again we observed the same benefits of albumin: only one child who received albumin died, out of a group of participants that included children treated as emergencies who were subsequently found to be ineligible for the trial. The results for Gelofusine, however, were not encouraging. The combined findings that death, severe allergic reaction, and acute neurological events were more common in the Gelofusine group suggested that albumin, rather than a cheaper substitute, should be taken forward into the next phase. This was supported by the analysis of the combined data from three trials, including 238 children receiving volume expansion. While this small phase II study was not powered to prove that Gelofusine was superior to saline or albumin, the results suggest that Gelofusine is unlikely to offer any advantage over the cheaper saline solution. Given the continued controversy over the use of resuscitation fluids in the management of severe malaria, we suggest that this can only be resolved through a definitive clinical trial. Woodrow and Planche [16] have chosen a different interpretation. The evidence presented from two studies conducted in Gabon, one which assessed volume depletion in only 12 survivors [17] and the other larger study conducted in less critically unwell children [18], supports a position of equipoise—the basis which usually prompts the need for a definitive clinical trial.

Choice of fluid for resuscitation of septic shock

Objectives: To determine current practice in choice of fluid resuscitation in children following publication of a systematic review that demonstrated a higher mortality in patients treated with human albumin solution....

Cardiovascular Dysfunction in Sepsis and Septic Shock.

The optimal therapy for the treatment of sepsis and septic shock remains controversial. Many protocols are followed, using different strategies for initial resuscitation, cardiovascular monitoring, hemodynamic intervention, and eradication of infection. Overall, an aggressive approach to the management of cardiovascular dysfunction in septic shock is warranted. Initially, large volume fluid resuscitation is instituted. Our first choice of resuscitation fluid is 0.9% normal saline. Invasive hemodynamic monitoring using a flotation pulmonary artery catheter as well as invasive arterial blood pressure monitoring is a necessity in the hemodynamic management of septic shock. If the patient remains hypotensive (mean arterial pressure < 65 mm Hg) after adequate volume resuscitation has been established (pulmonary capillary wedge pressure 12 to 15 mm Hg), then vasopressor agents must be instituted. Our first choice is usually dopamine. In patients who remain hypotensive after maximal doses of dopamine are reached, norepinephrine is added. If these agents generate excessive tachycardia or if tachyarrhythmias develop, phenylephrine can be substituted or added. Inotropic agents are useful if the patient demonstrates hypotension with a low cardiac output state. Dobutamine is the agent of choice. We initiate broad-spectrum empiric antibiotics at presentation, modifying the exact regimen based on 1) site of infection; 2) prevailing organisms and antibiotic resistance patterns in the patient's environment; and 3) other specific risk factors (immunosuppression, chronic disease, exposure and vaccination history, invasive medical devices). When appropriate, aggressive surgical debridement is pursued. Currently, there are no clinical data to support the use of antagonists for sepsis mediators, although various clinical trials remain underway. Steroids are contraindicated except for adrenal replacement therapy.