Perioperative administration of buffered versus non-buffered crystalloid intravenous fluid to improve outcomes following adult surgical procedures (Review)

Background Perioperative fluid strategies influence clinical outcomes following major surgery. Many intravenous fluid preparations are based on simple solutions, such as normal saline, that feature an electrolyte composition that differs from that of physiological plasma. Buffered fluids have a theoretical advantage of containing a substrate that acts to maintain the body's acid-base status - typically a bicarbonate or a bicarbonate precursor such as maleate, gluconate, lactate, or acetate. Buffered fluids also provide additional electrolytes, including potassium, magnesium, and calcium, more closely matching the electrolyte balance of plasma. The putative benefits of buffered fluids have been compared with those of non-buffered fluids in the context of clinical studies conducted during the perioperative period. This review was published in 2012, and was updated in 2017. Objectives To review effects of perioperative intravenous administration of buffered versus non-buffered fluids for plasma volume expansion or maintenance, or both, on clinical outcomes in adults undergoing all types of surgery. Search methods We electronically searched the Clinicaltrials.gov major trials registry, the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 6) in the Cochrane Library, MEDLINE (1966 to June 2016), Embase (1980 to June 2016), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to June 2016). We handsearched conference abstracts and, when possible, contacted leaders in the field. We reran the search in May 2017. We added one potential new study of interest to the list of 'Studies awaiting classification' and will incorporate this trial into formal review findings when we prepare the review update. Selection criteria Only randomized controlled trials that compared buffered versus non-buffered intravenous fluids for surgical patients were eligible for inclusion. We excluded other forms of comparison such as crystalloids versus colloids and colloids versus different colloids. Data collection and analysis Two review authors screened references for eligibility, extracted data, and assessed risks of bias. We resolved disagreements by discussion and consensus, in collaboration with a third review author. We contacted trial authors to request additional information when appropriate. We presented pooled estimates for dichotomous outcomes as odds ratios (ORs) and for continuous outcomes as mean differences (MDs), with 95% confidence intervals (CIs). We analysed data via Review Manager 5.3 using fixed-effectmodels, and when heterogeneity was high (I-2 > 40%), we used random-effects models. Main results This review includes, in total, 19 publications of 18 randomized controlled trials with a total of 1096 participants. We incorporated five of those 19 studies (330 participants) after the June 2016 update. Outcome measures in the included studies were thematically similar, covering perioperative electrolyte status, renal function, and acid-base status; however, we found significant clinical and statistical heterogeneity among the included studies. We identified variable protocols for fluid administration and total volumes of fluid administered to patients intraoperatively. Trial authors variably reported outcome data at disparate time points and with heterogeneous patient groups. Consequently, many outcome measures are reported in small group sizes, reducing overall confidence in effect size, despite relatively low inherent bias in the included studies. Several studies reported orphan outcome measures. We did not include in the results of this review one large, ongoing study of saline versus Ringer's solution. We found insufficient evidence on effects of fluid therapies on mortality and postoperative organ dysfunction (defined as renal insufficiency leading to renal replacement therapy); confidence intervals were wide and included both clinically relevant benefit and harm: mortality (Peto OR 1.85, 95% CI 0.37 to 9.33; I-2 = 0%; 3 trials, 6 deaths, 276 participants; low-quality evidence); renal insufficiency (OR 0.82, 95% CI 0.34 to 1.98; I-2 = 0%; 4 trials, 22 events, 276 participants; low-quality evidence). We noted several metabolic differences, including a difference in postoperative pH measured at end of surgery of 0.05 units -lower in the non-buffered fluid group (12 studies with a total of 720 participants; 95% CI 0.04 to 0.07; I-2 = 61%). However, this difference was not maintained on postoperative day one. We rated the quality of evidence for this outcome as moderate. We observed a higher postoperative serum chloride level immediately after operation, with use of non-buffered fluids reported in 10 studies with a total of 530 participants (MD 6.77 mmol/L, 95% CI 3.38 to 10.17), and this difference persisted until day one postoperatively (five studies with a total of 258 participants; MD 8.48 mmol/L, 95% CI 1.08 to 15.88). We rated the quality of evidence for this outcome as moderate. Authors' conclusions Current evidence is insufficient to show effects of perioperative administration of buffered versus non-buffered crystalloid fluids on mortality and organ system function in adult patients following surgery. Benefits of buffered fluid were measurable in biochemical terms, particularly a significant reduction in postoperative hyperchloraemia and metabolic acidosis. Small effect sizes for biochemical outcomes and lack of correlated clinical follow-up data mean that robust conclusions on major morbidity and mortality associated with buffered versus non-buffered perioperative fluid choices are still lacking. Larger studies are needed to assess these relevant clinical outcomes.