Table 1.
Study Outcomes
| Outcome | Definition |
|---|---|
| Feasibility outcomes | |
| Proportion of eligible patients enrolled | >65% of eligible patients enrolled |
| Acceptability of EFIC | ≤10% of patients withdrawing from study after enrollment under EFIC or |
| >90% of EFIC-eligible patients enrolled with completion of study activities | |
| Adherence to group assignment | Absolute difference in proportion of total isotonic fluids administered as NS between groups of ≥65% or |
| ≥85% of subjects in NS arm received ≥90% of study fluid as NS and ≥80% of subjects in LR arm received ≥75% of study fluid as LRa | |
| Effectiveness outcomes | |
| MAKE30 | Major adverse kidney events at 30 days (defined as at least one of the following): |
| Death | |
| New renal replacement therapy | |
| Persistent kidney dysfunction at hospital discharge or 30 days (serum creatinine ≥2× baseline or median value for age if no baseline available) | |
| All-cause hospital mortality | Censored at 90 days |
| Hospital length of stay | Days from hospital admission until discharge |
| Hospital-free days out of 28 days | Days between enrollment and day 28 in which patient was alive and out of the hospital |
| New inpatient RRT | New continuous renal replacement therapy, hemodialysis, or peritoneal dialysis |
| Safety outcomes | All within 4 calendar days of randomization except thrombosis which was within 7 days |
| Hyperlactatemia | >4 mMol/L |
| Hyperkalemia | >6 mEq/L |
| Hypercalcemia | Ionized calcium > 1.35 mmol/L or total serum calcium > 12 mg/dL |
| Hypernatremia | >155 mEq/L |
| Hyponatremia | <128 mEq/L |
| Hyperchloremia | >110 mEq/L |
| Thrombosis | Therapy for new arterial or venous thrombus with systemic anticoagulant or |
| Clotting of intravenous catheter in subjects receiving ceftriaxone and LR | |
| Cerebral edema | Therapy with hyperosmolar therapy (hypertonic saline and/or mannitol) for radiographic and clinical determination of new impending or present brain herniation |
EFIC = exception from informed consent; LR = lactated Ringer’s; MAKE30 = major adverse kidney events within 30 days; NS = 0.9% normal saline; RRT = renal replacement therapy
a
Patients were eligible for enrollment after an initial 20 mL/kg fluid bolus, which was most commonly expected to be 0.9% saline. Thus, it was anticipated that patients randomized to lactated Ringer’s would receive at least one 0.9% saline bolus.