Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis

Abstract

IMPORTANCE Saline (0.9% sodium chloride), the fluid most commonly used to treat diabetic ketoacidosis (DKA), can cause hyperchloremic metabolic acidosis. Balanced crystalloids, an alternative class of fluids for volume expansion, do not cause acidosis and, therefore, may lead to faster resolution of DKA than saline. OBJECTIVE To compare the clinical effects of balanced crystalloids with the clinical effects of saline for the acute treatment of adults with DKA. DESIGN, SETTING, AND PARTICIPANTS This study was a subgroup analysis of adults with DKA in 2 previously reported companion trials-Saline Against Lactated Ringer's or Plasma-Lyte in the Emergency Department (SALT-ED) and the Isotonic Solutions and Major Adverse Renal Events Trial (SMART). These trials, conducted between January 2016 and March 2017 in an academic medical center in the US, were pragmatic, multiple-crossover, cluster, randomized clinical trials comparing balanced crystalloids vs saline in emergency department (ED) and intensive care unit (ICU) patients.This study included adults who presented to the ED with DKA, defined as a clinical diagnosis of DKA, plasma glucose greater than 250 mg/dL, plasma bicarbonate less than or equal to 18 mmol/L, and anion gap greater than 10 mmol/L. Data analysis was performed from January to April 2020. INTERVENTIONS Balanced crystalloids (clinician's choice of Ringer lactate solution or Plasma-LyteA solution) vs saline for fluid administration in the ED and ICU according to the same clusterrandomized multiple-crossover schedule. MAIN OUTCOMES AND MEASURESThe primary outcome was time between ED presentation and DKA resolution, as defined by American Diabetes Association criteria. The secondary outcome was time between initiation and discontinuation of continuous insulin infusion. RESULTS Among 172 adults included in this secondary analysis of cluster trials, 94 were assigned to balanced crystalloids and 78 to saline. The median (interquartile range [IQR]) age was 29 (24-45) years, and 90 (52.3%) were women. The median (IQR) volume of isotonic fluid administered in the ED and ICU was 4478 (3000-6372) mL. Cumulative incidence analysis revealed shorter time to DKA resolution in the balanced crystalloids group (median time to resolution: 13.0 hours; IQR: 9.5-18.8 hours) than the saline group (median: 16.9 hours; IQR: 11.9-34.5 hours) (adjusted hazard ratio[aHR] = 1.68; 95% CI, 1.18-2.38; P = .004). Cumulative incidence analysis also revealed shorter time to insulin infusion discontinuation in the balanced crystalloids group (median: 9.8 hours; IQR: 5.1-17.0 (continued) Key Points Question Does using a balanced crystalloid solution instead of saline for fluid therapy in adults with diabetic ketoacidosis (DKA) lead to faster resolution of DKA? Findings In this subgroup analysis of 172 adults with DKA from 2 large cluster randomized clinical trials comparing balanced crystalloids and saline, the median time to DKA resolution was 13.0 hours with balanced crystalloids and 16.9 hours with saline, a significant difference. Me...

Saline Compared to Balanced Crystalloid in Patients With Diabetic Ketoacidosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…One study ( 28 ) reported the subgroup of DKA patients from two linked cluster RCTs ( 14 , 15 ) and was treated as a single RCT for the purposes of our analysis. These linked cluster RCTs enrolled a total of 172 patients with DKA; however, after applying the design effect and sample size reduction, we used a functional sample size of 106 patients.…”

“…One trial ( 27 ) used both Ringer’s lactate and PlasmaLyte due to a shortage in Ringer’s lactate that occurred during the study period. Another trial ( 28 ) allowed for the use of either Ringer’s lactate or PlasmaLyte at the discretion of the treating clinical team. Supplemental Table 4 ( http://links.lww.com/CCX/A890 ) presents risk of bias of the included RCTs.…”

“…Only two RCTs ( 28 , 31 ) reported renal endpoints and even when reported were heterogeneous in how the outcome was captured, and thus, we were unable to pool.…”

Normal Saline Versus Low Chloride Solutions in Treatment of Diabetic Ketoacidosis: A Systematic Review of Clinical Trials

“…One study reported the duration of insulin infusion in adults (Self et al [8]) for DKA. The study reported normal saline requiring more time, 13.4 h (11-17.9), than 9.8 hours (5.1-17) in balanced solutions before switching to subcutaneous insulin.…”

Analysis of a DKA protocol: Laboratory tests and outcomes

“…These study results suggest that balanced crystalloids may be preferable to saline for acute management of adults with DKA. 7 A Cochrane review in 2016 analyzed five small RCTs (total n = 201) comparing subcutaneous injections of insulin analogues (lispro or aspart) to regular insulin IV infusions in patients with mild to moderate DKA. The study revealed that there was no statistical difference in time to resolution of DKA (approximately 11 hours) or rates of hypoglycemia.…”