A Randomized Noninferiority Trial to Compare Enteral to Parenteral Phosphate Replacement on Biochemistry, Waste, and Environmental Impact and Healthcare Cost in Critically Ill Patients With Mild to Moderate Hypophosphatemia.

Objectives: Hypophosphatemia occurs frequently. Enteral, rather than IV, phosphate replacement may reduce fluid replacement, cost, and waste.
Design: Prospective, randomized, parallel group, noninferiority clinical trial.
Setting: Single center, 42-bed state trauma, medical and surgical ICUs, from April 20, 2022, to July 1, 2022.
Patients: Patients with serum phosphate concentration between 0.3 and 0.75 mmol/L.
Interventions: We randomized patients to either enteral or IV phosphate replacement using electronic medical record-embedded program.
Measurement and Main Results: Our primary outcome was serum phosphate at 24 hours with a noninferiority margin of 0.2 mmol/L. Secondary outcomes included cost savings and environmental waste reduction and additional IV fluid administered. The modified intention-to-treat cohort comprised 131 patients. Baseline phosphate concentrations were similar between the two groups. At 24 hours, mean ( sd ) serum phosphate concentration were enteral 0.89 mmol/L (0.24 mmol/L) and IV 0.82 mmol/L (0.28 mmol/L). This difference was noninferior at the margin of 0.2 mmol/L (difference, 0.07 mmol/L; 95% CI, -0.02 to 0.17 mmol/L). When assigned IV replacement, patients received 408 mL (372 mL) of solvent IV fluid. Compared with IV replacement, the mean cost per patient was ten-fold less with enteral replacement ($3.7 [$4.0] vs. IV: $37.7 [$31.4]; difference = $34.0 [95% CI, $26.3-$41.7]) and weight of waste was less (7.7 g [8.3 g] vs. 217 g [169 g]; difference = 209 g [95% CI, 168-250 g]). C O2 emissions were 60-fold less for comparable phosphate replacement (enteral: 2 g producing 14.2 g and 20 mmol of potassium dihydrogen phosphate producing 843 g of C O2 equivalents).
Conclusions: Enteral phosphate replacement in ICU is noninferior to IV replacement at a margin of 0.2 mmol/L but leads to a substantial reduction in cost and waste.
Competing Interests: Drs. Nguyen’s, Panganiban’s, and Ali Abdelhamid’s institutions received funding from the Clive and Vera Ramaciotti Foundations. Dr. Nguyen’s institution received funding from the Fox Family Foundation. Dr. Ali Abdelhamid’s institution received funding from the Intensive Care Foundation of Australia and New Zealand and the Victorian Medical Research Acceleration Fund. The remaining authors have disclosed that they do not have any potential conflicts of interest.
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