Dual receptor therapy with pituitrin for spinal cord injury-induced diabetes insipidus: A propensity-matched retrospective cohort study.

PURPOSE: Spinal cord injury (SCI)-induced diabetes insipidus (DI) presents a unique therapeutic challenge due to concurrent autonomic hypotension unresponsive to conventional desmopressin. This study evaluates the clinical efficacy of Pituitrin, a synthetic vasopressin analog with dual V1a/V2 receptor agonism, designed to simultaneously address antidiuretic hormone deficiency and hemodynamic instability in acute SCI-related DI.

METHODS: In this retrospective propensity-matched cohort study, 317 consecutive acute SCI patients (2010 -2021) were screened, with 60 (18.9%) developing DI. Patients were stratified into a Pituitrin-treated group (2014 - 2021, n = 30) and historical controls (2010 - 2013, n = 30). Propensity score matching (1:1 nearest-neighbor, caliper = 0.2 standard deviation) adjusted for age, American Spinal Injury Association (ASIA) grade, injury level (cervical/thoracic), concurrent mild brain injury (Glasgow coma scale 13 - 15), and treatment era covariates, yielding 23 matched pairs. Post-matching groups demonstrated balanced baseline characteristics with cervical injury prevalence 95.7% and ASIA grade A/B injuries 100%. The intervention group received protocolized Pituitrin infusion (initial 1 U/h, titrated 0.5 - 5 U/h based on urine output) with fluid restriction (<2000 mL/day), while controls received standard care including desmopressin and vasopressors as needed. Primary outcomes included DI duration (days to urine output <3000 mL/day concurrent with serum sodium ≥135 mmol/L), in-hospital mortality, and hospitalization length.

RESULTS: This study of 317 acute SCI patients (84% male) revealed DI developed in 18.9% (60/317), with striking cervical predominance (57 (31.0%) cervical vs. 3 (4.9%) thoracic SCI; χ2 = 21.4, p < 0.001). In propensity score-matched cohorts (23 pairs balanced for age, ASIA grade, injury level, and era). Early Pituitrin therapy demonstrated transformative efficacy: DI duration reduced by 7.6 days (4.4 ± 1.5 vs. 12.0 ± 2.6 days; 95% confidence interval (CI): 6.4 - 8.8, p < 0.001), 26% absolute mortality reduction (number needed to treat (NNT) = 3.85; p = 0.014), and shortened median hospitalization by 5 days (14 vs. 19 days, p = 0.008). Cervical ASIA A/B patients exhibited maximal benefit with 24% mortality reduction (NNT = 4.17, p = 0.014) and universal hemodynamic stabilization-Pituitrin eliminated vasopressor need in 87% of cases (vs. 23/30 controls requiring norepinephrine; risk difference = 0.63, NNT = 1.59). Notably, 100% of DI cases demonstrated autonomic hypotension preceding hyponatremia, with treatment initiation within 24 h of diagnosis accelerating recovery (r = -0.818, p < 0.001). The intervention proved exceptionally safe, with only 1 (3.3%) experiencing transient headaches.

CONCLUSION: This study establishes the first evidence-based protocol for dual V1a/V2 receptor targeting in SCI-induced DI, demonstrating that early Pituitrin administration achieves rapid antidiuresis (median 8-day resolution) while stabilizing hemodynamics (87% vasopressor independence). The 26% absolute mortality reduction (NNT = 3.85) and shortened hospitalization (Δ5 days) suggest promising therapeutic potential, especially for cervical complete injuries, and warrant further validation in larger prospective cohorts. These findings establish a novel treatment paradigm addressing the pathophysiological triad of arginine vasopressin deficiency, autonomic hypotension, and hyponatremia unique to acute SCI.