Balanced Solutions Versus Saline to Reduce AKI: A #NephJC Editorial on the BaSICS Trial

#NephJC is a recurring twitter-based journal club. #NephJC editorials highlight the discussed article and summarize key points from the NephJC TweetChat.Medicine has adopted the use of intravenous fluids as a foundational treatment some 185 years ago. Buffered saline solutions were first used in the resuscitation of patients during the London cholera epidemic of 1832.1Cosnett J.E. The origins of intravenous fluid therapy.Lancet. 1989; 1: 768-771Abstract PubMed Scopus (75) Google Scholar Intravenous fluids are still the primary intervention to treat shock. Despite this long history, fundamental questions regarding the content, timing, rate, and amount of fluid remain unanswered.2Cecconi M. Hofer C. Teboul J.L. et al.Fluid challenges in intensive care: the FENICE study: a global inception cohort study.Intensive Care Med. 2015; 41: 1529-1537Crossref PubMed Scopus (338) Google Scholar In this editorial, we discuss the literature around the use of balanced solutions and kidney injury. Balanced solutions are variously referred to in the literature as “buffered saline solutions,” “balanced multielectolyte solutions,” “chloride-restricted solutions,” or “balanced crystalloids” and have in common a lower chloride concentration (typically 98-110 mmol/L), addition of a buffer (lactate, gluconate, and/or acetate), and a small amount of other electrolytes (potassium, calcium, or magnesium).Until recently, the resuscitation fluid of choice, especially for internists, was normal saline. It is cheap, widely available, and familiar. In 2012, Yunos et al3Yunos N.M. Bellomo R. Hegarty C. Story D. Ho L. Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.JAMA. 2012; 308: 1566-1572Crossref PubMed Scopus (803) Google Scholar conducted a prospective, open-label, sequential-period pilot study in 760 patients admitted to a multidisciplinary intensive care unit (ICU), comparing a chloride-restricted resuscitation strategy with a chloride-liberal resuscitation strategy. During the 6-month control period, all patients admitted to the ICU received normal saline, which was followed by a phase-out period of 6 months. Following the phase-out period, all ICU patients received chloride-restricted fluids (Plasma-Lyte 148, Hartmann’s solution, chloride-poor 20% albumin) for the next 6 months. They reported a significant reduction in acute kidney injury (AKI) and requirement of kidney replacement therapy (KRT) with a chloride-restrictive strategy.3Yunos N.M. Bellomo R. Hegarty C. Story D. Ho L. Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.JAMA. 2012; 308: 1566-1572Crossref PubMed Scopus (803) Google Scholar Although the article reports AKI as the primary outcome, the initial outcome according to ClinicalTrials.gov was the change in the mean base excess during hospitalization.4Yunos N.M. Chloride High Level Of Resuscitation Infusion Delivered Evaluation (CHLORIDE).https://clinicaltrials.gov/ct2/show/NCT00885404Date accessed: September 27, 2021Google ScholarIn 2015, Young et al5Young P. Bailey M. Beasley R. et al.Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial.JAMA. 2015; 314: 1701-1710Crossref PubMed Scopus (437) Google Scholar published the SPLIT (0.9% Saline vs Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy) trial, a cluster-randomized trial of normal saline versus Plasma-Lyte conducted in 4 ICUs in New Zealand. They did not find any difference in AKI or the need for KRT.5Young P. Bailey M. Beasley R. et al.Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial.JAMA. 2015; 314: 1701-1710Crossref PubMed Scopus (437) Google Scholar Then, in 2018, the SMART (Isotonic Solutions and Major Adverse Renal Events Trial) and SALT-ED (Saline Against Lactated Ringer’s or Plasma-Lyte in the Emergency Department) pragmatic trials were published.6Self W.H. Semler M.W. Wanderer J.P. et al.Balanced crystalloids versus saline in noncritically ill adults.N Engl J Med. 2018; 378: 819-828Crossref PubMed Scopus (302) Google Scholar,7Semler M.W. Self W.H. Wanderer J.P. et al.Balanced crystalloids versus saline in critically ill adults.N Engl J Med. 2018; 378: 829-839Crossref PubMed Scopus (568) Google Scholar Both these were single-center, open-label, cluster-randomized trials, in which the intravenous solutions were alternated every month. The SALT-ED trial was conducted in the emergency department, and the SMART trial was conducted in ICUs. The SALT-ED trial reported no difference in hospital-free days between the groups (balanced crystalloid vs normal saline). However, the secondary outcome, which was major adverse kidney events (a composite of death because of any cause, initiation of KRT, and persistent kidney dysfunction, with the latter defined as an inability to recover 50% of the baseline estimated glomerular filtration rate when evaluated up to 90 days after discharge), was lower in the balanced crystalloid group than in the saline group (odds ratio, 0.82; 95% confidence interval, 0.70-0.95). The SMART trial similarly showed that balanced crystalloids reduced major adverse kidney events than the saline group (odds ratio, 0.91; 95% confidence interval, 0.84-0.99). Although positive, the SMART and SALT-ED trials were neither blinded nor randomized at the individual patient level, and some questioned the effect sizes given the small amount of fluid administered (see Fig 1 for a comparison of all major studies in this field).The BaSICS TrialBalanced Solutions in Intensive Care Study (BaSICS) was a multicenter, randomized controlled trial with a 2 × 2 factorial design comparing balanced crystalloids to normal saline and slow versus fast infusion among critically ill patients.8Zampieri F.G. Machado F.R. Biondi R.S. et al.Effect of intravenous fluid treatment with a balanced solution vs 0.9% saline solution on mortality in critically ill patients: the BaSICS randomized clinical trial.JAMA. 2021; 326: 1-12Google Scholar It was conducted in 75 Brazilian ICUs from May 2017 to March 2020. Physicians, patients, investigators, and outcome assessors were all blinded. The detailed eligibility are in ICU patients with or on and not with AKI on or with or were in the for the BaSICS patients at 1 of the than 90 or or for at for or of for and for or acute 6 of or death or or in the of after acute kidney Balanced Solutions in Intensive Care intensive care mean replacement were randomized to a balanced solution (Plasma-Lyte or 0.9% saline at 2 infusion and of fluids by was The primary outcome was the were the need for KRT, of and at days and were ICU and the of of patients were to a balanced solution, and received 0.9% normal saline The mean was and the mean was of the patients were admitted to the ICU after and received crystalloid fluid 90 patients to the balanced solutions versus patients to the saline solution was no significant between the 2 and infusion or between groups for the primary The mortality rate was in patients with injury balanced solution than in the saline solution vs The on was in the balanced crystalloid group than in the saline in the of AKI or need for were ICU and of were between was no with balanced solutions to normal saline for any clinical outcome or in any NephJC on the BaSICS and conducted 2 the with the is the intravenous fluid for the ICU crystalloid or saline the balanced solutions were by of outcome, and of BaSICS trial clinical Balanced Solutions in Intensive Care the was that the SALT-ED and SMART trials in a change for as in the change was the replacement of normal saline solution with Ringer’s solution in the care D. et fluid resuscitation and therapy in Care Med. 2021; PubMed Scopus Google Scholar not by the BaSICS to a of from the SMART and SALT-ED trials, as the cluster-randomized the small amount of fluid and the outcome by a change in than a death or the of balanced solutions as Ringer’s solution has reported to than saline of intravenous J 2018; PubMed Scopus Google Scholar However, the of that article in during the that the of of that the of Ringer’s solution has to in with normal saline solution, Plasma-Lyte from the SMART and SALT-ED trials were a reduction in major adverse kidney events was the primary outcome in the trial and the secondary outcome in the the in the BaSICS trial was the of difference in and was some a difference in was trial in to that the BaSICS trial did have for a reduction in mortality of with the of with the The of a difference in mortality patients and not a significant difference (see Fig for Although was some of normal saline to especially given the of normal saline and Ringer’s The did that the of fluids used did than the of which fluid is for (balanced solutions and saline the in the fluid is the Plasma-Lyte 148 versus Saline trial, a multicenter, randomized controlled trial comparing the of Plasma-Lyte 148 versus normal saline solution on mortality among critically ill patients that was published after the to the BaSICS trial, this trial reported no difference between the of death or AKI among critically ill in the ICU with the use of balanced solution with normal et al.Balanced solution versus saline in critically ill adults.N Engl J Med. PubMed Scopus Google Scholar trial in this is for which the of Plasma-Lyte 148 versus 0.9% saline on in kidney et for for a randomized controlled trial the effect of intravenous fluid therapy with Plasma-Lyte 148 versus 0.9% saline on in kidney Google Scholar It is that years after intravenous fluids were we are still to fundamental questions regarding and the as or the of intravenous fluids not to #NephJC is a recurring twitter-based journal club. #NephJC editorials highlight the discussed article and summarize key points from the NephJC #NephJC is a recurring twitter-based journal club. #NephJC editorials highlight the discussed article and summarize key points from the NephJC #NephJC is a recurring twitter-based journal club. #NephJC editorials highlight the discussed article and summarize key points from the NephJC has adopted the use of intravenous fluids as a foundational treatment some 185 years ago. Buffered saline solutions were first used in the resuscitation of patients during the London cholera epidemic of 1832.1Cosnett J.E. The origins of intravenous fluid therapy.Lancet. 1989; 1: 768-771Abstract PubMed Scopus (75) Google Scholar Intravenous fluids are still the primary intervention to treat shock. Despite this long history, fundamental questions regarding the content, timing, rate, and amount of fluid remain unanswered.2Cecconi M. Hofer C. Teboul J.L. et al.Fluid challenges in intensive care: the FENICE study: a global inception cohort study.Intensive Care Med. 2015; 41: 1529-1537Crossref PubMed Scopus (338) Google Scholar In this editorial, we discuss the literature around the use of balanced solutions and kidney injury. Balanced solutions are variously referred to in the literature as “buffered saline solutions,” “balanced multielectolyte solutions,” “chloride-restricted solutions,” or “balanced crystalloids” and have in common a lower chloride concentration (typically 98-110 mmol/L), addition of a buffer (lactate, gluconate, and/or acetate), and a small amount of other electrolytes (potassium, calcium, or recently, the resuscitation fluid of choice, especially for internists, was normal saline. It is cheap, widely available, and familiar. In 2012, Yunos et al3Yunos N.M. Bellomo R. Hegarty C. Story D. Ho L. Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.JAMA. 2012; 308: 1566-1572Crossref PubMed Scopus (803) Google Scholar conducted a prospective, open-label, sequential-period pilot study in 760 patients admitted to a multidisciplinary intensive care unit (ICU), comparing a chloride-restricted resuscitation strategy with a chloride-liberal resuscitation strategy. During the 6-month control period, all patients admitted to the ICU received normal saline, which was followed by a phase-out period of 6 months. Following the phase-out period, all ICU patients received chloride-restricted fluids (Plasma-Lyte 148, Hartmann’s solution, chloride-poor 20% albumin) for the next 6 months. They reported a significant reduction in acute kidney injury (AKI) and requirement of kidney replacement therapy (KRT) with a chloride-restrictive strategy.3Yunos N.M. Bellomo R. Hegarty C. Story D. Ho L. Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.JAMA. 2012; 308: 1566-1572Crossref PubMed Scopus (803) Google Scholar Although the article reports AKI as the primary outcome, the initial outcome according to ClinicalTrials.gov was the change in the mean base excess during hospitalization.4Yunos N.M. Chloride High Level Of Resuscitation Infusion Delivered Evaluation (CHLORIDE).https://clinicaltrials.gov/ct2/show/NCT00885404Date accessed: September 27, 2021Google Scholar In 2015, Young et al5Young P. Bailey M. Beasley R. et al.Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial.JAMA. 2015; 314: 1701-1710Crossref PubMed Scopus (437) Google Scholar published the SPLIT (0.9% Saline vs Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy) trial, a cluster-randomized trial of normal saline versus Plasma-Lyte conducted in 4 ICUs in New Zealand. They did not find any difference in AKI or the need for KRT.5Young P. Bailey M. Beasley R. et al.Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial.JAMA. 2015; 314: 1701-1710Crossref PubMed Scopus (437) Google Scholar Then, in 2018, the SMART (Isotonic Solutions and Major Adverse Renal Events Trial) and SALT-ED (Saline Against Lactated Ringer’s or Plasma-Lyte in the Emergency Department) pragmatic trials were published.6Self W.H. Semler M.W. Wanderer J.P. et al.Balanced crystalloids versus saline in noncritically ill adults.N Engl J Med. 2018; 378: 819-828Crossref PubMed Scopus (302) Google Scholar,7Semler M.W. Self W.H. Wanderer J.P. et al.Balanced crystalloids versus saline in critically ill adults.N Engl J Med. 2018; 378: 829-839Crossref PubMed Scopus (568) Google Scholar Both these were single-center, open-label, cluster-randomized trials, in which the intravenous solutions were alternated every month. The SALT-ED trial was conducted in the emergency department, and the SMART trial was conducted in ICUs. The SALT-ED trial reported no difference in hospital-free days between the groups (balanced crystalloid vs normal saline). However, the secondary outcome, which was major adverse kidney events (a composite of death because of any cause, initiation of KRT, and persistent kidney dysfunction, with the latter defined as an inability to recover 50% of the baseline estimated glomerular filtration rate when evaluated up to 90 days after discharge), was lower in the balanced crystalloid group than in the saline group (odds ratio, 0.82; 95% confidence interval, 0.70-0.95). The SMART trial similarly showed that balanced crystalloids reduced major adverse kidney events than the saline group (odds ratio, 0.91; 95% confidence interval, 0.84-0.99). Although positive, the SMART and SALT-ED trials were neither blinded nor randomized at the individual patient level, and some questioned the effect sizes given the small amount of fluid administered (see Fig 1 for a comparison of all major studies in this The BaSICS TrialBalanced Solutions in Intensive Care Study (BaSICS) was a multicenter, randomized controlled trial with a 2 × 2 factorial design comparing balanced crystalloids to normal saline and slow versus fast infusion among critically ill patients.8Zampieri F.G. Machado F.R. Biondi R.S. et al.Effect of intravenous fluid treatment with a balanced solution vs 0.9% saline solution on mortality in critically ill patients: the BaSICS randomized clinical trial.JAMA. 2021; 326: 1-12Google Scholar It was conducted in 75 Brazilian ICUs from May 2017 to March 2020. Physicians, patients, investigators, and outcome assessors were all blinded. The detailed eligibility are in ICU patients with or on and not with AKI on or with or were in the for the BaSICS patients at 1 of the than 90 or or for at for or of for and for or acute 6 of or death or or in the of after acute kidney Balanced Solutions in Intensive Care intensive care mean replacement were randomized to a balanced solution (Plasma-Lyte or 0.9% saline at 2 infusion and of fluids by was The primary outcome was the were the need for KRT, of and at days and were ICU and the of of patients were to a balanced solution, and received 0.9% normal saline The mean was and the mean was of the patients were admitted to the ICU after and received crystalloid fluid 90 patients to the balanced solutions versus patients to the saline solution was no significant between the 2 and infusion or between groups for the primary The mortality rate was in patients with injury balanced solution than in the saline solution vs The on was in the balanced crystalloid group than in the saline in the of AKI or need for were ICU and of were between was no with balanced solutions to normal saline for any clinical outcome or in any NephJC on the BaSICS and conducted 2 the with the is the intravenous fluid for the ICU crystalloid or saline the balanced solutions were by the was that the SALT-ED and SMART trials in a change for as in the change was the replacement of normal saline solution with Ringer’s solution in the care D. et fluid resuscitation and therapy in Care Med. 2021; PubMed Scopus Google Scholar not by the BaSICS to a of from the SMART and SALT-ED trials, as the cluster-randomized the small amount of fluid and the outcome by a change in than a death or the of balanced solutions as Ringer’s solution has reported to than saline of intravenous J 2018; PubMed Scopus Google Scholar However, the of that article in during the that the of of that the of Ringer’s solution has to in with normal saline solution, Plasma-Lyte from the SMART and SALT-ED trials were a reduction in major adverse kidney events was the primary outcome in the trial and the secondary outcome in the the in the BaSICS trial was the of difference in and was some a difference in was trial in to that the BaSICS trial did have for a reduction in mortality of with the of with the The of a difference in mortality patients and not a significant difference (see Fig for Although was some of normal saline to especially given the of normal saline and Ringer’s The did that the of fluids used did than the of which fluid is for (balanced solutions and saline the in the fluid is the Plasma-Lyte 148 versus Saline trial, a multicenter, randomized controlled trial comparing the of Plasma-Lyte 148 versus normal saline solution on mortality among critically ill patients that was published after the to the BaSICS trial, this trial reported no difference between the of death or AKI among critically ill in the ICU with the use of balanced solution with normal et al.Balanced solution versus saline in critically ill adults.N Engl J Med. PubMed Scopus Google Scholar trial in this is for which the of Plasma-Lyte 148 versus 0.9% saline on in kidney et for for a randomized controlled trial the effect of intravenous fluid therapy with Plasma-Lyte 148 versus 0.9% saline on in kidney Google Scholar It is that years after intravenous fluids were we are still to fundamental questions regarding and the as or the of intravenous fluids not to The BaSICS TrialBalanced Solutions in Intensive Care Study (BaSICS) was a multicenter, randomized controlled trial with a 2 × 2 factorial design comparing balanced crystalloids to normal saline and slow versus fast infusion among critically ill patients.8Zampieri F.G. Machado F.R. Biondi R.S. et al.Effect of intravenous fluid treatment with a balanced solution vs 0.9% saline solution on mortality in critically ill patients: the BaSICS randomized clinical trial.JAMA. 2021; 326: 1-12Google Scholar It was conducted in 75 Brazilian ICUs from May 2017 to March 2020. Physicians, patients, investigators, and outcome assessors were all blinded. The detailed eligibility are in ICU patients with or on and not with AKI on or with or were in the for the BaSICS patients at 1 of the than 90 or or for at for or of for and for or acute 6 of or death or or in the of after acute kidney Balanced Solutions in Intensive Care intensive care mean replacement were randomized to a balanced solution (Plasma-Lyte or 0.9% saline at 2 infusion and of fluids by was The primary outcome was the were the need for KRT, of and at days and were ICU and the of of patients were to a balanced solution, and received 0.9% normal saline The mean was and the mean was of the patients were admitted to the ICU after and received crystalloid fluid 90 patients to the balanced solutions versus patients to the saline solution was no significant between the 2 and infusion or between groups for the primary The mortality rate was in patients with injury balanced solution than in the saline solution vs The on was in the balanced crystalloid group than in the saline in the of AKI or need for were ICU and of were between was no with balanced solutions to normal saline for any clinical outcome or in any Balanced Solutions in Intensive Care Study (BaSICS) was a multicenter, randomized controlled trial with a 2 × 2 factorial design comparing balanced crystalloids to normal saline and slow versus fast infusion among critically ill patients.8Zampieri F.G. Machado F.R. Biondi R.S. et al.Effect of intravenous fluid treatment with a balanced solution vs 0.9% saline solution on mortality in critically ill patients: the BaSICS randomized clinical trial.JAMA. 2021; 326: 1-12Google Scholar It was conducted in 75 Brazilian ICUs from May 2017 to March 2020. Physicians, patients, investigators, and outcome assessors were all blinded. The detailed eligibility are in ICU patients with or on and not with AKI on or with or were in the patients at 1 of the than 90 or or for at for or of for and for or acute 6 of or death or or in the of after ICU patients at 1 of the than 90 or or for at for or of for and for or acute 6 of or death or or in the of after acute kidney Balanced Solutions in Intensive Care intensive care mean replacement The were randomized to a balanced solution (Plasma-Lyte or 0.9% saline at 2 infusion and of fluids by was The primary outcome was the were the need for KRT, of and at days and were ICU and the of of patients were to a balanced solution, and received 0.9% normal saline The mean was and the mean was of the patients were admitted to the ICU after and received crystalloid fluid 90 patients to the balanced solutions versus patients to the saline solution was no significant between the 2 and infusion or between groups for the primary The mortality rate was in patients with injury balanced solution than in the saline solution vs The on was in the balanced crystalloid group than in the saline in the of AKI or need for were ICU and of were between was no with balanced solutions to normal saline for any clinical outcome or in any NephJC on the BaSICS and conducted 2 the with the is the intravenous fluid for the ICU crystalloid or saline the balanced solutions were by the was that the SALT-ED and SMART trials in a change for as in the change was the replacement of normal saline solution with Ringer’s solution in the care D. et fluid resuscitation and therapy in Care Med. 2021; PubMed Scopus Google Scholar not by the BaSICS to a of from the SMART and SALT-ED trials, as the cluster-randomized the small amount of fluid and the outcome by a change in than a death or the of balanced solutions as Ringer’s solution has reported to than saline of intravenous J 2018; PubMed Scopus Google Scholar However, the of that article in during the that the of of that the of Ringer’s solution has to in with normal saline solution, Plasma-Lyte from the SMART and SALT-ED trials were a reduction in major adverse kidney events was the primary outcome in the trial and the secondary outcome in the the in the BaSICS trial was the of difference in and was some a difference in was trial in to that the BaSICS trial did have for a reduction in mortality of with the of with the The of a difference in mortality patients and not a significant difference (see Fig for Although was some of normal saline to especially given the of normal saline and Ringer’s The did that the of fluids used did than the of which fluid is for (balanced solutions and saline the in the fluid is the Plasma-Lyte 148 versus Saline trial, a multicenter, randomized controlled trial comparing the of Plasma-Lyte 148 versus normal saline solution on mortality among critically ill patients that was published after the to the BaSICS trial, this trial reported no difference between the of death or AKI among critically ill in the ICU with the use of balanced solution with normal et al.Balanced solution versus saline in critically ill adults.N Engl J Med. PubMed Scopus Google Scholar trial in this is for which the of Plasma-Lyte 148 versus 0.9% saline on in kidney et for for a randomized controlled trial the effect of intravenous fluid therapy with Plasma-Lyte 148 versus 0.9% saline on in kidney Google Scholar It is that years after intravenous fluids were we are still to fundamental questions regarding and the as or the of intravenous fluids not to The NephJC on the BaSICS and conducted 2 the with the is the intravenous fluid for the ICU crystalloid or saline the balanced solutions were by During the was that the SALT-ED and SMART trials in a change for as in the change was the replacement of normal saline solution with Ringer’s solution in the care D. et fluid resuscitation and therapy in Care Med. 2021; PubMed Scopus Google Scholar not by the BaSICS to a of from the SMART and SALT-ED trials, as the cluster-randomized the small amount of fluid and the outcome by a change in than a death or the of balanced solutions as Ringer’s solution has reported to than saline of intravenous J 2018; PubMed Scopus Google Scholar However, the of that article in during the that the of of that the of Ringer’s solution has to in with normal saline solution, Plasma-Lyte The from the SMART and SALT-ED trials were a reduction in major adverse kidney events was the primary outcome in the trial and the secondary outcome in the the in the BaSICS trial was the of difference in and was some a difference in was trial in to that the BaSICS trial did have for a reduction in mortality of with the of with the The of a difference in mortality patients and not a significant difference (see Fig for Although was some of normal saline to especially given the of normal saline and Ringer’s The did that the of fluids used did than the of which fluid is for (balanced solutions and saline the in the fluid is the Plasma-Lyte 148 versus Saline trial, a multicenter, randomized controlled trial comparing the of Plasma-Lyte 148 versus normal saline solution on mortality among critically ill patients that was published after the to the BaSICS trial, this trial reported no difference between the of death or AKI among critically ill in the ICU with the use of balanced solution with normal et al.Balanced solution versus saline in critically ill adults.N Engl J Med. PubMed Scopus Google Scholar trial in this is for which the of Plasma-Lyte 148 versus 0.9% saline on in kidney et for for a randomized controlled trial the effect of intravenous fluid therapy with Plasma-Lyte 148 versus 0.9% saline on in kidney Google Scholar It is that years after intravenous fluids were we are still to fundamental questions regarding and the as or the of intravenous fluids not to and M. from the of of has an in and has on the of and The that have no and on the of NephJC as and NephJC is a that in and has and and no for these by 1 with from the in March 27,

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