Table 2 Summary of the key interventional clinical studies that have compare 0.9 % saline to buffered crystalloid fluid in adult patients

The SPLIT trial. 2015 [27]

Multicentre, double-blind, cluster randomised, double crossover trial comparing 0.9 % saline with Plasma-Lyte 148®; n= 2262

• There was no significant difference between group in rates of AKI or AKI requiring RRT

• There was no significant difference between groups in survival to day 90

Smith et al. 2015 [28]

Single centre, double-blind RCT comparing 0.9 % saline with Plasma-Lyte A® in critically ill trauma patients; n=18

• Patients receiving 0.9 % saline had significantly lower serum chloride and bicarbonate concentration

• Patients receiving Plasma-Lyte A® had a quicker fibrin build up and cross linking (α angle) at 6 hours after infusion

• No difference between groups in coagulation tests or blood products received at 6 hours

Young et al. 2014 [29]

Single centre, double-blind RCT comparing 0.9 % saline with Plasma-Lyte A® in patient presenting to ED with severe acute trauma; n=46

• Patients receiving 0.9 % saline had an increase in serum chloride concentration and decrease in serum pH

• No significant differences in mortality hospital length of stay, blood transfusion requirements or utilization of resources

Cieza et al. 2013 [30]

Single centre, open label RCT comparing 0.9 % saline with Ringer’s lactate in patients with severe dehydration secondary to choleriform diarrhea; n=40

• Patients receiving 0.9 % saline had lower serum pH at 2 and 4 hours

• No difference between in serum creatinine, lactate or potassium concentration

Hasman et al. 2012 [31]

Single centre, double-blind RCT comparing either 0.9 % saline, Ringer's lactate or Plasma-Lyte® in patients presenting to ED with dehydration; n= 90

• Patients receiving 0.9 % saline had a significantly lower serum pH and lower serum bicarbonate concentration

• No difference between groups in chloride, potassium, or sodium concentrations

Van Zyl et al. 2012 [32]

Multicentre, double-blind RCT of Ringer’s lactate versus 0.9 % saline in patients presenting to ED with diabetic ketoacidosis; n=54

• There was no significant difference between groups in time interval for correction of acidosis

• Patient receiving 0.9 % saline a significantly shorter time to lower blood glucose

• No difference between groups in hospital length of stay

Mahler et al. 2011 [33]

Single centre, double-blind RCT comparing either 0.9 % saline with Plasma-Lyte A® in patients presenting to ED with diabetic ketoacidosis; n= 45

• Patients receiving 0.9 % saline had significantly higher serum chloride and lower bicarbonate concentration

Wu et al. 2011 [34]

Multicentre, open label RCT comparing 0.9 % saline with Ringer’s lactate in patients diagnosed with acute pancreatitis; n=40

• Patients receiving Ringer’s lactate had lower rates of SIRS and lower CRP concentration at 24 hours

• No difference between groups in development of complications or hospital length of stay

Cho et al. 2007 [35]

Multicentre, single-blind RCT of Ringer’s lactate versus 0.9 % saline in patients presenting to ED with rhabdomyolysis; n=28

• Patients receiving 0.9 % saline had a significantly higher serum chloride and sodium concentration and lower serum pH

• There was no significant difference between groups in time interval for normalisation of creatine kinase

The SPLIT- Major Surgery trial. 2015

Prospective phase 4, single centre blinded study investigating the safety and efficacy of using 0.9 % saline with Plasma-Lyte® 148 as fluid therapy in adult patients undergoing major surgery; n=1100

• There was no significant difference between groups in rates of AKI

• There were no significant difference between groups in the development of postoperative complications or length of hospital stay

• Patients who received 0.9 % saline developed a transient hyperchloremic metabolic acidosis on postoperative day 1

Potura et al. 2015 [36]

Single centre, open label RCT comparing 0.9 % saline with Elomel Isoton®(low chloride, acetate buffered crystalloid) in patients undergoing renal transplantation; n=150

• Significantly more patients receiving 0.9 % saline required intra-operative inotrope support

• Patients receiving 0.9 % saline had a significantly lower base excess and higher serum chloride concentration

• No difference between groups in post-operative urine output, creatinine, blood urea nitrogen or need for RRT

Song et al. 2015 [37]

Single centre, open label RCT comparing 0.9 % saline with Plasma-Lyte® in patients undergoing spinal surgery; n=50

• Patients receiving 0.9 % saline had lower pH, base excess, and bicarbonate concentration and higher serum chloride concentration

• Patients receiving Plasma-Lyte® had significantly higher urine output

• No difference between groups in rotation thromboelastometry analysis, estimated blood loss or transfusion requirements

Hafizah et al. 2015 [38]

Single centre, open label RCT comparing 0.9 % saline with Sterofundin® ISO patients undergoing neurosurgery (low chloride, acetate buffered crystalloid); n=30

• Patients receiving 0.9 % saline had a significantly lower serum pH and higher serum chloride and sodium concentration

Kim et al. 2013 [39]

Single centre, blinded RCT comparing either 0.9 % saline with Plasma-Lyte® in patients undergoing renal transplantation; n= 60

• Patients receiving 0.9 % saline had lower pH and base excess values

• No difference between groups in post-operative urine output, creatinine or need for RRT

Modi et al. 2012 [40]

Single centre, double-blind RCT comparing 0.9 % saline with Ringer's lactate in patients undergoing renal transplantation; n= 74

• Patients receiving 0.9 % saline had lower serum pH and base excess values

• No difference between groups in post-operative urine output or creatinine

Heidari et al. 2011 [41]

Single centre, double-blind RCT comparing 0.9 % saline with Ringer’s lactate and 5% saline in patients undergoing lower abdominal surgery; n=90

• A higher proportion of patients that had received 0.9 % saline had experienced vomiting 6 hours post-operatively

Hadimioglu et al. 2008 [42]

Single centre, double-blind RCT comparing either 0.9 % saline, Ringer's lactate or Plasma-Lyte® in patients undergoing renal transplantation; n= 90

• Patients receiving 0.9 % saline had an increase in serum chloride concentration and decrease in serum pH

• Patients receiving Ringer’s lactate had a significantly increased serum lactate concentration

• There was no significant difference between in postoperative creatinine or need for RRT

Khajavi et al. 2008 [43]

Single centre, double-blind RCT comparing 0.9 % saline with Ringer's lactate in patients undergoing renal transplantation; n= 52

• Patient receiving 0.9 % saline had a significantly lower serum pH and higher serum potassium concentration at the end of the operation

Chin et al. 2006 [44]

Single centre, open label RCT comparing 0.9 % saline with Ringer’s lactate, 0.9 % saline with dextrose 5 % in non-diabetic patients undergoing elective surgery; n=50

• No difference between groups in serum urea, sodium or potassium concentration

• Dextrose 5 % resulted in significant, albeit transient hyperglycemia, even in non-diabetic patients

Karaca et al. 2006 [45]

Single centre, single-blinded RCT comparing 0.9 % saline with Ringer’s lactate and 4 % gelatin polysuccinate in patients undergoing transurethral prostatectomy under spinal anesthesia; n=60

• No difference between groups nausea, vomiting, dizziness and post spinal hearing loss.

Chanimov et al. 2006 [46]

Single centre, double-blinded RCT comparing 0.9 % saline with Ringer’s lactate in patients undergoing Cesarean section; n=40

• No difference between groups in inotrope requirements

• No significant differences in the Apgar scores at 1 and 5 min or infant well-being

O’Malley et al. 2005 [47]

Single centre, double blind RCT comparing 0.9 % saline with Ringer’s lactate in patients undergoing renal transplantation; n=51

• Significantly more patients receiving 0.9 % saline required intra-operative treatment for metabolic acidosis and hyperkalemia

• No difference between groups in post-operative urine output, creatinine or need for RRT

Takil et al. 2002 [48]

Single centre, open label RCT comparing 0.9 % saline with Ringer’s lactate in patients undergoing spinal surgery; n=30

• Patients receiving 0.9 % saline had an increase in serum chloride, sodium concentration and decrease in serum pH

• No difference between groups in intraoperative hemodynamic variables or hospital and ICU lengths of stay

Waters et al. 2001 [49]

Single centre, double-blind RCT comparing 0.9 % saline with Ringer’s lactate in patients undergoing abdominal aortic aneurysm surgery; n=66

• Patients receiving 0.9 % saline had an increase in serum chloride, sodium concentration and decrease in serum pH

• Patients receiving 0.9 % saline received a greater volume of platelets

• No difference between groups in estimated blood loss, postoperative complications, hospital and ICU lengths of stay

Scheingraber et al. 1999 [50]

Single centre, open label RCT comparing 0.9 % saline with Ringer’s lactate in patients undergoing gynecologic surgery; n=24

• Patients receiving 0.9 % saline had an increase in serum chloride concentration and decrease in serum pH

Ramanathan et al. 1984 [551]

Single centre, open label RCT comparing 0.9 % saline with Ringer’s lactate, Ringer’s lactate with dextrose 5 % and Plasma-Lyte A® in patients undergoing Cesarean section; n=60

• Patients receiving 0.9 % saline had an decrease in serum pH

• No difference between groups in blood pressure or inotrope requirements