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Maintenance intravenous fluids are the most frequently ordered medications for hospitalized children. Since the American Association of Pediatrics published national guidelines, there has been an increased reflexive use of isotonic solutions, especially 0.9% saline, as a prophylaxis against hyponatremia. In this educational review, we discuss the potential deleterious effects of using 0.9% saline, including the development of hyperchloremia, metabolic acidosis, acute kidney injury, hyperkalemia, and a proinflammatory state. Balanced solutions with anion buffers cause relatively minimal harm when used in most children. While the literature supporting one fluid choice over the other is variable, we highlight the benefits of balanced solutions over saline and the importance of prescribing fluid therapy that is individualized for each patient. [ABSTRACT FROM AUTHOR]

Fluid resuscitation during diabetic ketoacidosis (DKA) is most frequently performed with 0.9% saline despite its high chloride and sodium concentration. Balanced Electrolyte Solutions (BES) may prove a more physiological alternative, but convincing evidence is missing. We aimed to compare the efficacy of 0.9% saline to BES in DKA management. MEDLINE, Cochrane Library, and Embase databases were searched for relevant studies using predefined keywords (from inception to 27 November 2021). Relevant studies were those in which 0.9% saline (Saline‐group) was compared to BES (BES‐group) in adults admitted with DKA. Two reviewers independently extracted data and assessed the risk of bias. The primary outcome was time to DKA resolution (defined by each study individually), while the main secondary outcomes were changes in laboratory values, duration of insulin infusion, and mortality. We included seven randomized controlled trials and three observational studies with 1006 participants. The primary outcome was reported for 316 patients, and we found that BES resolves DKA faster than 0.9% saline with a mean difference (MD) of −5.36 [95% CI: −10.46, −0.26] hours. Post‐resuscitation chloride (MD: −4.26 [−6.97, −1.54] mmoL/L) and sodium (MD: −1.38 [−2.14, −0.62] mmoL/L) levels were significantly lower. In contrast, levels of post‐resuscitation bicarbonate (MD: 1.82 [0.75, 2.89] mmoL/L) were significantly elevated in the BES‐group compared to the Saline‐group. There was no statistically significant difference between the groups regarding the duration of parenteral insulin administration (MD: 0.16 [−3.03, 3.35] hours) or mortality (OR: −0.67 [0.12, 3.68]). Studies showed some concern or a high risk of bias, and the level of evidence for most outcomes was low. This meta‐analysis indicates that the use of BES resolves DKA faster than 0.9% saline. Therefore, DKA guidelines should consider BES instead of 0.9% saline as the first choice during fluid resuscitation. [ABSTRACT FROM AUTHOR]

Background and Aims: The choice of intravenous fluids is important in patients with traumatic brain injury (TBI), where large volumes may be required for resuscitation. Our study aimed to compare 0.9% normal saline (NS) with balanced crystalloid (Plasmalyte) in TBI patients in terms of metabolic and coagulation profile, brain relaxation score (BRS) and renal functions using serum urea, creatinine and urinary tissue inhibitor of metalloproteinases-2* insulin-like growth factor binding protein-7, [TIMP-2]*[IGFBP7], value to assess the risk of acute kidney injury. Methods: This randomised controlled trial on 90 TBI patients undergoing emergency craniotomy and subdural haematoma evacuation was conducted in a tertiary care institute. The patients were randomised to receive either NS (Group NS) or Plasmalyte (Group P) as the intraoperative maintenance fluid. The primary outcome measures included the potential of hydrogen (pH), base excess (BE) and chloride values from an arterial blood gas. The secondary outcomes were the coagulation profile, BRS and urinary [TIMP-2]*[IGFBP7]. The two groups’ metabolic profile differences were analysed using two-way repeated analysis of variance. BRS was analysed using the Mann–Whitney U test. A P value < 0.05 was considered to be statistically significant. Results: The pH and chloride values were significantly higher, and the BE values were significantly lower in Group P compared to Group NS (P < 0.001). Brain relaxation and coagulation profiles were comparable between the two groups. Serum creatinine (P = 0.002) and urinary [TIMP-2]*[IGFBP7] (P = 0.042) were significantly higher in the NS group. Conclusion: Plasmalyte maintains a more favourable metabolic profile than NS in TBI patients without affecting brain relaxation adversely.

Background and Aims: The choice of intravenous fluids is important in patients with traumatic brain injury (TBI), where large volumes may be required for resuscitation. Our study aimed to compare 0.9% normal saline (NS) with balanced crystalloid (Plasmalyte) in TBI patients in terms of metabolic and coagulation profile, brain relaxation score (BRS) and renal functions using serum urea, creatinine and urinary tissue inhibitor of metalloproteinases-2* insulin-like growth factor binding protein-7, [TIMP-2]*[IGFBP7], value to assess the risk of acute kidney injury. Methods: This randomised controlled trial on 90 TBI patients undergoing emergency craniotomy and subdural haematoma evacuation was conducted in a tertiary care institute. The patients were randomised to receive either NS (Group NS) or Plasmalyte (Group P) as the intraoperative maintenance fluid. The primary outcome measures included the potential of hydrogen (pH), base excess (BE) and chloride values from an arterial blood gas. The secondary outcomes were the coagulation profile, BRS and urinary [TIMP-2]*[IGFBP7]. The two groups' metabolic profile differences were analysed using two-way repeated analysis of variance. BRS was analysed using the Mann-Whitney U test. A P value < 0.05 was considered to be statistically significant. Results: The pH and chloride values were significantly higher, and the BE values were significantly lower in Group P compared to Group NS (P < 0.001). Brain relaxation and coagulation profiles were comparable between the two groups. Serum creatinine (P = 0.002) and urinary [TIMP-2]*[IGFBP7] (P = 0.042) were significantly higher in the NS group. Conclusion: Plasmalyte maintains a more favourable metabolic profile than NS in TBI patients without affecting brain relaxation adversely. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a global health concern with significant economic impact. Optimal fluid therapy aims to restore intravascular volume, maintain cerebral perfusion pressure and blood flow, thus preventing secondary brain injury. While 0.9% saline (NS) is commonly used, concerns about acid-base and electrolyte imbalance and development of acute kidney injury (AKI) lead to consideration of balanced fluids as an alternative. This study aimed to compare the outcomes of patients with moderate to severe TBI treated with Sterofundin (SF) versus NS. A double-blinded randomised controlled trial of patients aged 18 to 65 years with TBI was conducted at the University Malaya Medical Centre from February 2017 to November 2019. Patients were randomly assigned to receive either NS or SF. The study fluids were administered for 72 h as continuous infusions or boluses. Participants, investigators, and staff were blinded to the fluid type. The primary outcome was in-hospital mortality. Relative risk (RR) with 95% confidence interval (CI) was calculated. A total of 70 patients were included in the analysis, with 38 in the NS group and 32 in the SF group. The in-hospital mortality rate were 3 (7.9%) in the NS group vs. 4 (12.5%) in the SF group, RR = 1.29 (95% CI, 0.64 to 2.59; p = 0.695). No patients developed AKI and required renal replacement therapy. ICP on day 3 was significantly higher in the SF group (18.60 ± 9.26) compared to 12.77 ± 3.63 in the NS group, (95% CI, −11.46 to 0.20; p = 0.037). There were no significant differences in 3-day biochemical parameters and cerebral perfusion pressure, ventilator-free days, length of ICU stay, or Glasgow Outcome Scale-Extended (GOS-E) score at 6 months. In patients with moderate to severe TBI, the use of SF was not associated with reduced in-hospital mortality, development of AKI, or improved 6-month GOS-E when compared to NS. [ABSTRACT FROM AUTHOR]

This review summarises some of my work on fluid and electrolyte balance over the past 25 years and shows how the studies have influenced clinical practice. Missing pieces in the jigsaw are filled in by summarising the work of others. The main theme is the biochemical, physiological and clinical problems caused by inappropriate use of saline solutions including the hyperchloraemic acidosis caused by 0.9% saline. The importance of accurate and near-zero fluid balance in clinical practice is also emphasised. Perioperative fluid and electrolyte therapy has important effects on clinical outcome in a U-shaped dose response fashion, in which excess or deficit progressively increases complications and worsens outcome. Salt and water overload, with weight gain in excess of 2.5 kg worsens surgical outcome, impairs gastrointestinal function and increases the risk of anastomotic dehiscence. Hyperchloraemic acidosis caused by overenthusiastic infusion of 0.9% saline leads to adverse outcomes and dysfunction of many organ systems, especially the kidney. Salt and water deficit causes similar adverse effects as fluid overload at the cellular level and also leads to worse outcomes. Serum albumin is shown to be affected mainly by dilution and inflammation and is not a good nutritional marker. These findings have been incorporated in the British consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical Patients (GIFTASUP) and National Institute for Health and Care Excellence (NICE) guidelines on intravenous fluid therapy in adults in hospital and are helping change clinical practice and improve outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Delayed graft function, or the requirement for dialysis due to poor kidney function, is a frequent complication of deceased donor kidney transplantation that is associated with inferior outcomes. Intravenous fluids with a high chloride content, such as isotonic sodium chloride (0.9% saline), are widely used in transplantation but may increase the risk of poor kidney function. The primary objective of the BEST-Fluids trial is to compare the effect of a balanced low-chloride crystalloid, Plasma-Lyte 148 (Plasmalyte), versus 0.9% saline on the incidence of DGF in deceased donor kidney transplant recipients. This article describes the statistical analysis plan for the trial. Methods and design BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-centre, double-blind, randomised controlled trial. Eight hundred patients (adults and children) in Australia and New Zealand with end-stage kidney disease admitted for a deceased donor kidney transplant were randomised to intravenous fluid therapy with Plasmalyte or 0.9% saline in a 1:1 ratio using minimization. The primary outcome is delayed graft function (dialysis within seven days post-transplant), which will be modelled using a log-binomial generalised linear mixed model with fixed effects for treatment group, minimization variables, and ischaemic time and a random intercept for study centre. Secondary outcomes including early kidney transplant function (a ranked composite of dialysis duration and the rate of graft function recovery), treatment for hyperkalaemia, and graft survival and will be analysed using a similar modelling approach appropriate for the type of outcome. Discussion BEST-Fluids will determine whether Plasmalyte reduces the incidence of DGF and has a beneficial effect on early kidney transplant outcomes relative to 0.9% saline and will inform clinical guidelines on intravenous fluids for deceased donor kidney transplantation. The statistical analysis plan describes the analyses to be undertaken and specified before completion of follow-up and locking the trial databases. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12617000358347 . Prospectively registered on 8 March 2017 ClinicalTrials.gov identifier NCT03829488 . Registered on 4 February 2019

Background: The use of hypotonic fluid, such as 0.45% saline, following kidney transplantation (KT) in children is associated with a high incidence of electrolyte imbalance, especially hyponatraemia. This can result in serious adverse events, such as cerebral oedema and seizures. The aim of this study was to investigate the incidence of electrolyte disturbance in children when 0.9% saline was the intravenous fluid used in the first 72 h following KT. Methods: This is a retrospective, observational study of 50 consecutive KT undertaken between January 2017 and January 2019 at a single centre. Results: The median age at KT was 9.2 years (IQR 4–14) and 16 (32%) were females. Thirty-two (64%) were living related donor (LRD) KT and 22 (44%) were carried out in children < 20 kg. The mean volume of fluid administered intra-operatively, and on Day 1, Day 2 and Day 3, were 73 ml/kg, 124 ml/kg, 97 ml/kg and 86 ml/kg, respectively. Hyponatraemia was noted in 4%, hypernatraemia in 18%, hyperkalaemia in 18%, hyperchloraemia in 68% and low bicarbonate was seen in 88%. Fifteen percent of the children had an episode of hyperglycaemia. None of the children developed symptomatic dyselectrolytaemia. There was delayed graft function (DGF) in 4 (8%) recipients — all deceased donor (DD) KT, including 2 who received donations after circulatory death. Conclusions: While the use of 0.9% saline is associated with a high incidence of electrolyte disturbances, including hyperkalaemia, it reduces the risk of hyponatraemia. None of the children developed a symptomatic electrolyte abnormality. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Background: 0.9% saline commonly used for resuscitation of septic patients might induce biochemical changes leading to detrimental effects. Ringer's lactate being a balanced crystalloid might be beneficial in such a scenario. Objectives: We undertook this study to explore in detail the effect of these fluids in the resuscitation of septic patients, and risks and benefits these two fluids would have on the overall prognosis of patients. Methods: This was an open-label randomized controlled trial undertaken in emergency medical services attached to the department of medicine at a tertiary care teaching hospital. One hundred sixty adult (⩾18 years old) medical patients admitted with the diagnosis of sepsis fulfilling eligibility criteria were included. They were randomly assigned to receive 0.9% saline or ringer's lactate. These fluids were given for the initial 24 h only, and after then, the type of fluid given was based on treating physician discretion. Various biochemical parameters were measured at baseline and various time points during the hospital stay. The primary outcome was to find out the incidence of hyperchloremia at 24 h from the time of randomization and during the hospital stay. The secondary outcomes were incidence of acute kidney injury, need for renal replacement therapy; differences in pH, bicarbonate, serum lactate, coagulation parameters, sequential organ failure assessment scores at various time points; and hospital/30-day mortality. Results: The baseline characteristics in both groups were comparable. At admission, each group had a serum chloride value which was comparable (p value: 0.595); however, at 24 and 48 h, a statistically significant difference was noticed, with 0.9% saline group having a higher mean serum chloride value (113.66 ± 10.04 v/s 108.98 ± 8.04 mEq/L, p value: 0.001 at 24 h) and (114.75 ± 9.51 v/s 111.12 ± 7.84 mEq/L, p value: 0.022 at 48 h). At 24 and 48 h post-randomization, the incidence of hyperchloremia was significantly higher in the 0.9% saline group (at 24 h, 0.9% saline: 75.0% v/s Ringer's lactate: 48.8%, p value: 0.001 and at 48 h, 0.9% saline: 77.2% v/s Ringer's lactate: 60.3%, p value: 0.022), although there was no difference in the incidence of hyperchloremia recorded during the hospital stay. Acute kidney injury incidence at 24 and 48 h post-randomization was significantly higher in the 0.9% saline group (at 24 h, 0.9% saline: 23.8% v/s Ringer's lactate: 10.0%, p value: 0.020 and at 48 h, 0.9% saline: 29.1% v/s Ringer's lactate: 15.4%, p value: 0.039). No significant differences in other secondary outcomes were observed. Conclusion: Higher incidence of hyperchloremia and a higher rate of acute kidney injury at 24 and 48 h after randomization were noted in the 0.9% saline group. [ABSTRACT FROM AUTHOR]

Background: Delayed graft function, or the requirement for dialysis due to poor kidney function, is a frequent complication of deceased donor kidney transplantation that is associated with inferior outcomes. Intravenous fluids with a high chloride content, such as isotonic sodium chloride (0.9% saline), are widely used in transplantation but may increase the risk of poor kidney function. The primary objective of the BEST-Fluids trial is to compare the effect of a balanced low-chloride crystalloid, Plasma-Lyte 148 (Plasmalyte), versus 0.9% saline on the incidence of DGF in deceased donor kidney transplant recipients. This article describes the statistical analysis plan for the trial.Methods and Design: BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-centre, double-blind, randomised controlled trial. Eight hundred patients (adults and children) in Australia and New Zealand with end-stage kidney disease admitted for a deceased donor kidney transplant were randomised to intravenous fluid therapy with Plasmalyte or 0.9% saline in a 1:1 ratio using minimization. The primary outcome is delayed graft function (dialysis within seven days post-transplant), which will be modelled using a log-binomial generalised linear mixed model with fixed effects for treatment group, minimization variables, and ischaemic time and a random intercept for study centre. Secondary outcomes including early kidney transplant function (a ranked composite of dialysis duration and the rate of graft function recovery), treatment for hyperkalaemia, and graft survival and will be analysed using a similar modelling approach appropriate for the type of outcome.Discussion: BEST-Fluids will determine whether Plasmalyte reduces the incidence of DGF and has a beneficial effect on early kidney transplant outcomes relative to 0.9% saline and will inform clinical guidelines on intravenous fluids for deceased donor kidney transplantation. The statistical analysis plan describes the analyses to be undertaken and specified before completion of follow-up and locking the trial databases.Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12617000358347 . Prospectively registered on 8 March 2017 ClinicalTrials.gov identifier NCT03829488 . Registered on 4 February 2019. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) have favorable characteristics that render them a potent therapeutic tool. We tested the characteristics of MSCs after temporal storage in various carrier solutions, such as 0.9% saline (saline), 5% dextrose solution (DS), heparin in saline, and Hartmann's solution, all of which are approved by the U.S. Food and Drug Administration (FDA). Phosphate-buffered saline, which does not have FDA approval, was also used as a carrier solution. We aimed to examine the effects of these solutions on the viability and characteristics of MSCs to evaluate their suitability and efficacy for the storage of canine adipose-derived MSCs (cADMSCs). Results: We stored the cADMSCs in the test carrier solutions in a time-dependent manner (1, 6, and 12 h) at 4 °C, and analyzed cell confluency, viability, proliferation, self-renewability, and chondrogenic differentiation. Cell confluency was significantly higher in 5% DS and lower in phosphate-buffered saline at 12 h compared to other solutions. cADMSCs stored in saline for 12 h showed the highest viability rate. However, at 12 h, the proliferation rate of cADMSCs was significantly higher after storage in 5% DS and significantly lower after storage in saline, compared to the other solutions. cADMSCs stored in heparin in saline showed superior chondrogenic capacities at 12 h compared to other carrier solutions. The expression levels of the stemness markers, Nanog and Sox2, as well as those of the MSC surface markers, CD90 and CD105, were also affected over time. Conclusion: Our results suggest that MSCs should be stored in saline, 5% DS, heparin in saline, or Hartmann's solution at 4 °C, all of which have FDA approval (preferable storage conditions: less than 6 h and no longer than 12 h), rather than storing them in phosphate-buffered saline to ensure high viability and efficacy. [ABSTRACT FROM AUTHOR]

Purpose: Bolus intravenous administration of 0.9% saline has been associated with the development of pulmonary edema, and increased mortality. An animal model has previously demonstrated that rapid intravenous administration of 0.9% saline was associated with non-hydrostatic lung injury with increased lung lavage protein. We hypothesized that this non-hydrostatic effect would also occur in human volunteers. Methods: In a randomized, cross-over study of 14 healthy male subjects, the lung lavage protein concentration and cardiorespiratory effects of an intervention with rapid intravenous administration of 30 mL/kg of 0.9% saline were compared with sham intervention. Bronchoalveolar lavage (BAL) was performed after fluid administration. Doppler echocardiography, lung ultrasound, pulmonary function tests, and blood sampling were performed before and after each intervention. Results: The BAL total protein concentration was greater after 0.9% saline administration than with sham (196.1 µg/mL (SD 87.6) versus 129.8 µg/mL (SD 55.4), respectively (p = 0.020). Plasma angiopoietin-2 concentration was also increased to 2.26 ng/mL (SD 0.87) after 0.9% saline administration compared with sham 1.53 ng/mL (SD 0.69) (p < 0.001). There were small increases in stroke volume (from 58 mL (IQR 51–74) to 66 mL (IQR 58–74), p = 0.045) and Doppler echocardiography left ventricle E/e' ratio (from 5.0 (IQR 4.5–6.0) to 5.7 (IQR 5.3–6.3), p = 0.007), but no changes to right ventricular function. Conclusion: Rapid intravenous administration of 0.9% saline leads to interstitial permeability pulmonary edema in healthy human volunteers. Further research is now warranted to understand these effects in critically ill patients. [ABSTRACT FROM AUTHOR]

Intravenous fluid administration in veterinary patients can alter coagulation function by several mechanisms. Both crystalloid and colloid fluids cause hemodilution, reducing platelet count and plasma coagulation protein concentrations. Hemodilution is associated with a hypercoagulable effect at low dilutions and a hypocoagulable effect at higher dilutions. Composition of crystalloid fluids likely has a minor effect, primarily dependent on fluid ion composition. Hypertonic crystalloids may also cause hypocoagulability. Colloids, both synthetic and natural, can cause hypocoagulability by several mechanisms beyond the effects of hemodilution. These include impaired platelet function, decreased plasma coagulation factor activity, impaired fibrin formation and crosslinking, and accelerated fibrinolysis. The vast majority of the veterinary literature investigates the hypocoagulable effects of hydroxyethyl starch–containing fluids using in vitro, experimental, and clinical studies. However, results are inconsistent, likely due to the varying doses and physicochemical properties of the specific fluid products across studies. In addition, some evidence exists for hypocoagulable effects of gelatin and albumin solutions. There is also evidence that these colloids increase the risk of clinical bleeding in people. Limitations of the veterinary evidence for the hypocoagulable effects of colloid fluids include a predominance of in vitro studies and in vivo studies using healthy subjects, which exclude the interaction of the effects of illness. Therefore, clinical relevance of these effects, especially for low-molecular-weight hydroxyethyl starch, is unknown. Firm recommendations about the most appropriate fluid to use in clinical scenarios cannot be made, although it is prudent to limit the dose of synthetic colloid in at-risk patients. Clinicians should closely monitor relevant coagulation assays and for evidence of hemorrhage in at-risk patients receiving any type of fluid therapy, especially in large volumes.

Abstract Background Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are life-threatening complications of diabetes mellitus which require prompt treatment with large volume crystalloid fluid administration. A variety of crystalloid fluids is currently available for use and differs in their composition and ion concentrations. While there are potential pros and cons for different crystalloid fluids, it remains unknown if any particular fluid confers a clinical outcome benefit over others in the treatment of hyperglycemic emergencies. Methods A systematic search of MEDLINE, Embase, and the Cochrane Library of Systematic Reviews will be conducted to identify eligible studies, which will include observational and interventional studies involving adult and pediatric patients admitted to the hospital with either DKA or HHS. The interventions will include intravenous treatment with 0.9% saline versus other buffered (Ringer’s lactate, Hartmann’s, etc.), and non-buffered (0.45% saline) crystalloid fluids. The primary outcome is mortality at the latest follow-up time point. Secondary outcomes will include mortality at specific time points, length of hospital stay, development of acute kidney injury, requirement for renal replacement therapy, altered level of consciousness, and the time to normalization of several serum biochemical parameters. Where appropriate, meta-analyses will be performed for the outcomes and conducted separately for adult and pediatric patient populations. Discussion DKA and HHS are dangerous complications of diabetes mellitus and account for significant morbidity and mortality. Given the importance of crystalloid fluid administration in the management of these conditions, a systematic synthesis of the existing evidence base will identify potential evidence gaps and may help guide future clinical practice.

Abstract Background Intravenous crystalloid solutions are administered commonly for critically ill patients. We performed this meta-analysis of randomized trials with trial sequential analysis (TSA) to evaluate effects of chloride content of intravenous crystalloid solutions on clinical outcomes among critically ill adult patients. Methods Electronic databases were searched up to June 1, 2018, for randomized trials of use of balanced crystalloids versus 0.9% saline solutions in critically ill adult patients. The outcome variables included mortality, renal outcomes, serum content alterations and organ function. Subgroup analysis was conducted according to patient settings, types or volume of crystalloid fluid, or among sepsis versus non-sepsis, TBI versus non-TBI or subpopulations by the categories of baseline kidney function. Random errors were evaluated by trial sequential analysis. Results Eight studies with 19,301 patients were analyzed. A trend of in-hospital survival benefit with no statistical difference could be observed with balanced crystalloids compared with 0.9% saline (RR 0.92, 95% CI 0.85–1.0, p = 0.06). The use of balanced crystalloid solutions was associated with longer RRT-free days (SMD 0.09, 95% CI 0.06–0.12, p

Context: It is common practice to avoid lactate-containing intravenous fluids in diabetic patients as it was hypothesized to cause hyperglycaemia by the conversion of lactate to glucose by hepatic gluconeogenesis. However, absence of sound theoretical basis, conflicting reports from numerous clinical trials and improved understanding of biochemistry have necessitated a closer scrutiny of this hypothesis. Aims: The present study aims to determine the effect of 0.9% saline and Ringer's lactate on blood glucose levels in the fasting diabetic surgical patients receiving spinal anaesthesia. Settings and design: The study is a prospective randomized trial conducted on adult patients aged 30 -- 85 years with well-controlled type 2 diabetes mellitus receiving spinal anaesthesia. Methods and material: 120 patients with well-controlled type 2 diabetes mellitus receiving spinal anaesthesia were randomized to receive either 1 litre of 0.9% saline or Ringer's lactate. Blood glucose levels were recorded using a glucometer by the pinprick method before and after infusion of 1 litre of the selected intravenous fluid. Statistical analysis: Data analysis was done using SPSS statistical package - Version 22.0. Student's unpaired 't' test was used to test the significance of difference between quantitative variables. A 'p' value less than 0.05 was taken to denote statistical significance. Results: Mean change in blood glucose levels after infusion of the intravenous fluid in 0.9% saline and Ringer's lactate groups were 3.68±15.2 mg/dl and - 0.15±16.5 mg/dl, respectively. The difference between the two groups was not statistically significant with a 'p' value of 0.188. Conclusions: Ringer's lactate solution, when compared to 0.9% saline, does not cause significant change in the mean blood glucose levels in fasting diabetic patients receiving spinal anaesthesia. [ABSTRACT FROM AUTHOR]

Recently, buffered salt solutions and 20% albumin (small volume resuscitation) have been advocated as an alternative fluid for intravenous resuscitation. The relative comparative efficacy and potential adverse effects of these solutions have not been evaluated. In a randomized, double blind, cross-over study of six healthy male subjects we compared the pulmonary and hemodynamic effects of intravenous administration of 30 ml/kg of 0.9% saline, Hartmann's solution and 4% albumin, and 6 ml/kg of 20% albumin (albumin dose equivalent). Lung tests (spirometry, ultrasound, impulse oscillometry, diffusion capacity, and plethysmography), two- to three-dimensional Doppler echocardiography, carotid applanation tonometry, blood gases, serum/urine markers of endothelial, and kidney injury were measured before and after each fluid bolus. Data were analyzed with repeated measures ANOVA with effect of fluid type examined as an interaction. Crystalloids caused lung edema [increase in ultrasound B line (P = 0.006) and airway resistance (P = 0.009)], but evidence of lung injury [increased angiopoietin-2 (P = 0.019)] and glycocalyx injury [increased synde- can (P = 0.026)] was only observed with 0.9% saline. The colloids caused greater left atrial stretch, decrease in lung volumes, and increase in diffusion capacity than the crystalloids, but without pulmonary edema. Stroke work increased proportionally to increase in preload with all four fluids (R² = 0.71). There was a greater increase in cardiac output and stroke volume after colloid administration, associated with a reduction in afterload. Hartmann's solution did not significantly alter ventricular performance. Markers of kidney injury were not affected by any of the fluids administrated. Bolus administration of 20% albumin is both effective and safe in healthy subjects. NEW & NOTEWORTHY Bolus administration of 20% albumin is both effective and safe in healthy subjects when compared with other commonly available crystalloids and colloidal solution. [ABSTRACT FROM AUTHOR]

Objective Administration of excess chloride in 0.9% normal saline (NS) decreases renal perfusion and glomerular filtration rate, thereby increasing the risk for acute kidney injury (AKI). In this study, the effect of NS versus Isolyte use during cardiac surgery on urinary levels of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor-binding protein 7 [TIMP-2] × [IGFBP7] and postoperative risk of AKI were examined. Design Prospective, randomized, and single-blinded trial. Setting Single university medical center. Participants Thirty patients over 18 years without chronic renal insufficiency or recent AKI undergoing elective cardiac surgery. Interventions Subjects were randomized to receive either NS or Isolyte during the intraoperative period. Measurements and Main Results The primary outcome was the change in urinary levels of [TIMP2] × [IGFBP7] from before surgery to 24 hours postoperatively. Secondary outcomes included serum creatinine pre- and postoperatively at 24 and 48 hours, serum chloride pre- and postoperatively at 24 and 48 hours, need for dialysis prior to discharge, and arterial pH measured 24 hours postoperatively. Sixteen patients received NS and 14 patients received Isolyte. Three patients developed AKI within the first 3 postoperative days, all in the NS group. The authors found increases in [TIMP-2] × [IGFBP7] in both groups. However, the difference in this increase between study arms was not significant (p = 0.92; -0.097 to 0.107). Conclusion The authors observed no change in urinary [TIMP-] × [IGFBP7] levels in patients receiving NS versus Isolyte during cardiac surgery. Future larger studies in patients at higher risk for AKI are recommended to evaluate the impact of high- versus lower-chloride solutions on the risk of postoperative AKI after cardiac surgery. [ABSTRACT FROM AUTHOR]

Background: Kidney transplant recipients often receive large volumes of intravenous fluid replacement in the perioperative period. Administration of 0.9% saline has previously been associated with acidosis, hyperkalaemia and acute kidney injury. The perioperative use of physiologically balanced replacement fluids may reduce the incidence of postoperative renal replacement therapy and hyperkalaemia. Methods: A retrospective review of consecutive renal transplants before and after a change in perioperative fluid prescription from 0.9% saline to Plasma-Lyte 148. Results: A total of 97 patients were included in the study, 59 receiving exclusively 0.9% saline and 38 receiving exclusively Plasma-Lyte. Patients in the Plasma-Lyte group were less likely to require emergency postoperative dialysis than those receiving 0.9% saline [odds ratio (OR) 0.15 (95% confidence interval 0.03-0.48), P=0.004], and these patients had more favourable biochemical parameters with less hyperkalaemia, less acidosis and better diuresis. Patients in the Plasma-Lyte group also had a shorter length of hospital stay (7 days versus 11 days; P<0.0001) and better graft function at 3months postoperatively (estimated glomerular filtration rate 51 versus 44mL/min/1.73m2; P=0.03); however, there was no difference in graft function at 1 year. Conclusions: Plasma-Lyte in the perioperative period is safe in renal transplantation and is associated with a favourable biochemical profile, including a reduced incidence of hyperkalaemia, better diuresis and less frequent use of renal replacement therapy early after surgery. In patients receiving Plasma-Lyte, graft function was better at 3 months, but this difference did not persist up to 1 year after transplantation [ABSTRACT FROM AUTHOR]

Objective To evaluate the effect of Plasma-Lyte 148 (PL-148) compared with 0.9% saline (saline) on blood product use and postoperative bleeding in patients admitted to the intensive care unit (ICU) following cardiac surgery. Design A post hoc subgroup analysis conducted within a multicenter, double-blind, cluster-randomized, double-crossover study (study 1) and a prospective, single-center nested-cohort study (study 2). Setting Tertiary-care hospitals. Participants Adults admitted to the ICU after cardiac surgery requiring crystalloid fluid therapy as part of the 0.9% saline vs. PL-148 for ICU fluid therapy (SPLIT) trial. Interventions Blinded saline or PL-148 for 4 alternating 7-week blocks. Measurements and Main Results 954 patients were included in study 1; 475 patients received PL-148, and 479 received saline. 128 of 475 patients (26.9%) in the PL-148 group received blood or a blood product compared with 94 of 479 patients (19.6%) in the saline group (OR [95% confidence interval], 1.51 [1.11-2.05]; p = 0.008). In study 2, 131 patients were allocated to PL-148 and 120 patients were allocated to saline. There were no differences between groups in chest drain output from the time of arrival in the ICU until 12 hours postoperatively (geometric mean, 566 mL for the PL-148 group v 547 mL in the saline group; p = 0.60). Conclusions The findings did not support the hypothesis that using PL-148 for fluid therapy in ICU following cardiac surgery reduces transfusion requirements compared to saline. The significantly increased proportion of patients receiving blood or blood product with allocation to PL-148 compared to saline was unexpected and requires verification through further research. [ABSTRACT FROM AUTHOR]

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Rapid intravenous (iv) infusion of 0.9% saline alters respiratory mechanics in healthy subjects. However, the relative cardiovascular and respiratory effects of bolus iv crystalloid vs. colloid are unknown. Six healthy male volunteers were given 30 ml/kg iv 0.9% saline, 4% albumin, and 5% glucose at a rate of 100 ml/min on 3 separate days in a double-blinded, randomized crossover study. Impulse oscillometry, spirometry, lung volumes, diffusing capacity (DLCO), and blood samples were measured before and after fluid administration. Lung ultrasound B-line score (indicating interstitial pulmonary edema) and Doppler echocardiography indices of cardiac preload were measured before, midway, immediately after, and 1 h after fluid administration. Infusion of 0.9% saline increased small airway resistance at 5 Hz (P = 0.04) and lung ultrasound B-line score (P = 0.01) without changes in Doppler echocardiography measures of preload. In contrast, 4% albumin increased DLCO, decreased lung volumes, and increased the Doppler echocardiography mitral E velocity (P = 0.001) and E-to-lateral/septal e' ratio, estimated blood volume, and N-terminal pro B-type natriuretic peptide (P = 0.01) but not lung ultrasound B-line score, consistent with increased pulmonary blood volume without interstitial pulmonary edema. There were no significant changes with 5% glucose. Plasma angiopoietin-2 concentration increased only after 0.9% saline (P = 0.001), suggesting an inflammatory mechanism associated with edema formation. In healthy subjects, 0.9% saline and 4% albumin have differential pulmonary effects not attributable to passive fluid filtration. This may reflect either different effects of these fluids on active signaling in the pulmonary circulation or a protective effect of albumin. [ABSTRACT FROM AUTHOR]

Introduction In multi-level lumbar spinal fusion surgery yielding a large amount of blood loss, choice of fluid for volume resuscitation is an important issue since it can influence acid-base status, coagulation, and patients’ outcome. This study compared the effect of plasmalyte to 0.9% saline on coagulation assessed by rotation thromboelastometry (ROTEM) and acid-base balance in the aforementioned patients. Methods Fifty patients were randomly allocated to receive either 0.9% saline or plasmalyte during operation and until postoperative 12 h. ROTEM was performed at 10 min after anesthetic induction and end of surgery. Arterial blood gas analyses were serially performed from 10 min after anesthetic induction until postoperative 12 h. Fluid balance, blood loss, and transfusion requirement were assessed. Results ROTEM variables showed sporadic deterioration in both groups after surgery without intergroup differences. Intraoperatively, arterial pH, base excess, and bicarbonate concentrations were lower and serum chloride concentrations were higher in the 0.9% saline group compared with the plasmalyte group. The differences in base excess and bicarbonate concentrations persisted until postoperative 12 h. Fluid balance, blood loss, and transfusion requirement were similar between the groups while urine output was greater in the plasmalyte group compared with the 0.9% saline group (3.2 ± 1.6 ml/kg/h vs. 1.8 ± 1.1 ml/kg/h, p = 0.001). Conclusion In contrast to plasmalyte, fluid therapy with 0.9% saline resulted in transient hyperchloremic acidosis in patients undergoing multi-level lumbar spinal fusion, while coagulation assessed by ROTEM analysis and the amount of blood loss were similar between the groups. [ABSTRACT FROM AUTHOR]

In the acute care setting, the type and amount of fluid administered has a significant impact on patient outcomes. In particular, 0.9% saline infusions are known to cause or exacerbate hyperchloremia. The studies presented evaluate possible complications from 0.9% saline infusions. These studies compared administration of 0.9% saline with lactated ringer or plasmalyte in the acute care setting. In each trial, the patients who were randomized to receive 0.9% saline infusions had a more severe acidosis from increased serum chloride levels. From the available data, chloride-restrictive intravenous fluid such as plasmalyte appears to reduce acid-base disturbances and improve patient outcomes. [ABSTRACT FROM AUTHOR]

The author discusses aspects of the use of saline as solution for crystalloid fluid resuscitation in acutely ill patients. He examines the effect of saline administration on acid-base physiology which can cause metabolic acidosis. The author cites the outcomes of patients treated with fluid therapy in the intensive care unit (ICU).

Objective: To compare the effect of a balanced isotonic crystalloid solution with that of 0.9% sodium chloride on the acid–base and electrolyte status of cats with urethral obstruction. Design: Randomized prospective clinical trial. Setting: Academic veterinary emergency room. Animals: Sixty-eight cats with naturally occurring urethral obstruction. Interventions: Cats were randomized to receive either a balanced isotonic crystalloid solution (Normosol-R, n=39) or 0.9% sodium chloride ( n=29) for fluid therapy. Baseline venous blood gas and blood electrolyte values were obtained at the time of admission and at intervals during the course of therapy. Measurements and main results: Baseline values were similar between groups. Cats receiving Normosol-R had a significantly higher blood pH at 12 hours, a significantly greater increase in blood pH from baseline at 6 and 12 hours, as well as a significantly higher blood bicarbonate concentration at 12 hours and a significantly greater increase in blood bicarbonate from baseline at 6 and 12 hours. Conversely, the increase in blood chloride from baseline was significantly higher at 2, 6, and 12 hours in cats receiving 0.9% sodium chloride. There were no significant differences in the rate of decline of blood potassium from baseline between groups. Subgroup analysis of hyperkalemic cats (K+>6.0 mmol/L) and acidemic cats (pH<7.3) yielded similar findings. Conclusions: While both crystalloid solutions appear safe and effective for fluid therapy in cats with urethral obstruction, the use of a balanced electrolyte solution may allow more rapid correction of blood acid–base status within the first 12 hours of fluid therapy. The use of a potassium-containing balanced electrolyte solution does not appear to affect the rate of normalization of blood potassium in treated cats with urethral obstruction. [ABSTRACT FROM AUTHOR]

Summary: Background & aims: We aimed to trace the historical origins of 0.9% saline, how it came to be used so commonly today, and to consider whether its continued use can be justified. Methods: We searched the Medline, Science Citation Index, ScienceDirect and Google™ databases using the key words saline, physiological, salt solution, sodium chloride, 0.9%, intravenous, injection, fluid, cholera, resuscitation, parenteral, history, historical and origins. Results: The use of 0.9% saline is believed to have originated during the cholera pandemic that swept across Europe in 1831. However, an examination of the composition of the fluids used by the pioneering physicians of that era reveals solutions that bear no resemblance to 0.9% or so-called ‘normal’ saline which appears to have very little scientific or historical basis for its routine use, except for Hamburger''s in vitro studies of red cell lysis. Conclusions: The currently used 0.9% saline solution is without convincing historical basis. Given that the composition of 0.9% sodium chloride is dissimilar to most solutions used in the past, and is in no way ‘normal’ or ‘physiological’, our current practice may be based on historical fallacy and misconception. [Copyright &y& Elsevier]

Intravenous fluid administration in veterinary patients can alter coagulation function by several mechanisms. Both crystalloid and colloid fluids cause hemodilution, reducing platelet count and plasma coagulation protein concentrations. Hemodilution is associated with a hypercoagulable effect at low dilutions and a hypocoagulable effect at higher dilutions. Composition of crystalloid fluids likely has a minor effect, primarily dependent on fluid ion composition. Hypertonic crystalloids may also cause hypocoagulability. Colloids, both synthetic and natural, can cause hypocoagulability by several mechanisms beyond the effects of hemodilution. These include impaired platelet function, decreased plasma coagulation factor activity, impaired fibrin formation and crosslinking, and accelerated fibrinolysis. The vast majority of the veterinary literature investigates the hypocoagulable effects of hydroxyethyl starch-containing fluids using in vitro , experimental, and clinical studies. However, results are inconsistent, likely due to the varying doses and physicochemical properties of the specific fluid products across studies. In addition, some evidence exists for hypocoagulable effects of gelatin and albumin solutions. There is also evidence that these colloids increase the risk of clinical bleeding in people. Limitations of the veterinary evidence for the hypocoagulable effects of colloid fluids include a predominance of in vitro studies and in vivo studies using healthy subjects, which exclude the interaction of the effects of illness. Therefore, clinical relevance of these effects, especially for low-molecular-weight hydroxyethyl starch, is unknown. Firm recommendations about the most appropriate fluid to use in clinical scenarios cannot be made, although it is prudent to limit the dose of synthetic colloid in at-risk patients. Clinicians should closely monitor relevant coagulation assays and for evidence of hemorrhage in at-risk patients receiving any type of fluid therapy, especially in large volumes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Boyd, Brainard and Smart.)

Introduction: 0.9% saline and Ringer's lactate are the two most common resuscitation crystalloid fluids. 0.9% saline may lead to hyperchloraemic metabolic acidosis and may be associated with impaired kidney function and death. Few large multicentre randomised trials have been conducted to evaluate the effect of these two fluids on clinically important outcomes., Methods: FLUID is a pragmatic pilot cluster randomised crossover trial in which four hospitals will be randomised to normal saline or Ringer's lactate for 14 weeks, then crossover to the alternative fluid for the subsequent 14 weeks after 1 to 3 week transition. With waiver of informed consent, all adult and paediatric patients admitted to participating sites will be included in the FLUID trial except for neonates. Primary feasibility outcome is study fluid protocol adherence (target:≥80%). Secondary feasibility outcomes include time to research ethics board (REB) approval and readiness to trial initiation (≤3 months from REB submission and approval). Primary (composite of death or re-admission to hospital in first 90 days of index hospitalisation) and secondary clinical outcomes for the future large FLUID trial will be described. Protocol adherence will be collected by site at specified time points. All clinical data will be obtained at patient level through provincial health administrative data held at the Institute for Clinical Evaluative Sciences (ICES). Event rates for the primary and secondary outcomes will be described using frequencies and proportions with 95% CIs. Intracluster and interperiod correlation coefficients will be calculated from population-level data available at ICES., Ethics and Dissemination: The study protocol has been approved by the Ottawa Health Science Research Ethics Board. The FLUID pilot will determine feasibility, and ICES data across all potential sites in Ontario will allow calculation of sample size parameter estimates to inform the design and implementation of the large trial., Trial Registration Number: NCT02721485; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)