{"doi":"10.1002/ajh.27509","title":"Emergency department intravenous fluid resuscitation and renal outcomes among adults with sickle cell disease","abstract":"Acidosis and increased tonicity in plasma can mediate pathologic changes in the membrane and cytoplasm of sickle red blood cells (sRBCs). These changes contribute to intravascular hemolysis, endothelial damage, and endothelial adhesion with propensity to microvascular occlusion, resulting in vaso-occlusive episodes (VOE) and end organ damage.1 Kidney dysfunction, in particular, is common among adults with sickle cell disease (SCD) and is a major contributor to early mortality.1, 2 While adults with SCD seek emergency department (ED) care for VOE and other complications that may lead to hospitalization, selecting the most appropriate interventions, such as which crystalloid for hydration, remains a challenge and is still being studied.3 How these interventions impact end-organ injury also remain unknown. Evidence-based guidelines for optimal treatment of SCD in the ED do not recommend a specific fluid type,4 but recent pre-clinical models suggest increased extracellular fluid tonicity (i.e., higher sodium and chloride) can increase sRBC stiffness and endothelial adhesion, and subsequently higher risk of VOE under physiologic conditions.5 Further, normal saline (NS), which is the most commonly administered intravenous (IV) fluid in the ED, can cause hyperchloremic metabolic acidosis which may contribute to negative outcomes in patients with SCD.6, 7 The seminal Saline Against Lactated Ringer's or Plasma-Lyte in the Emergency Department (SALT-ED) trial was a single-center, pragmatic, unblinded, multiple-crossover prospective randomized controlled trial (RCT) that enrolled non-critically ill adult patients treated in the Vanderbilt University Medical Center ED and randomized patients to receive NS or balanced crystalloids (BC), primarily lactated Ringer's (LR) based on calendar month (Figure S1).7 NS increased risk of major adverse kidney events and death at 30 days (i.e., MAKE30; Data S1) and in-hospital metabolic acidosis changes compared to more physiologic and balanced IV fluids like LR, which is hypotonic relative to plasma and has a more physiologic pH and osmolarity compared to NS (Table S1). In this intention-to-treat subgroup analysis of SCD patients enrolled in the study, our primary objective was to evaluate the same variables as SALT-ED specifically at the index visit (first visit). The primary aim was to determine if there were differences in length of stay (LoS) between those patients with SCD receiving NS versus BC, and secondary aims included evaluating the changes in kidney-related outcomes and suggestion of in-hospital metabolic acidosis by evaluating electrolyte status. We hypothesized that NS exposure would worsen all of these in those patients enrolled who had SCD. Exploratory aims included a per-protocol analysis of index visits and reviewing all ED visits among those with SCD and comparing all results to the overall SALT-ED cohort. Comparisons between the overall SALT-ED cohort and those with SCD are outlined in Table S2. There were 247 ED visits among 97 unique adults with SCD during the trial period (~2.5 visits/patient), with N = 126 (51%) visits allocated to the BC group and N = 121 (49%) in the NS group (Table S3). Most documented chief complaints in the ED were VOE-related (Table S4). Patients with SCD were younger, more likely to identify as female and Black, and have a lower baseline serum creatinine (SCr) compared to the overall SALT-ED population (Tables S5 and S6). Total ED crystalloid volume and adherence to randomized IV fluid assignment were similar between all patients and those with SCD. Strikingly, patients with SCD enrolled in the SALT-ED trial had a 3.5 times higher odds of achieving a MAKE30 composite endpoint than the entire cohort. While no patients with SCD died during the study, there were 200 patient deaths in the overall study. At the index visits, N = 58 adults with SCD were randomized to BC and N = 39 to NS (Table 1). Only one patient in the BC arm received Plasma-Lyte, and thus, ","journal":"American Journal of Hematology","year":2024,"id":505198,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":439255,"name":"Jeffrey D. Lebensburger","orcid":"0000-0001-5011-1022","position":1,"is_corresponding":false},{"id":608327,"name":"Wayne Rosamond","orcid":null,"position":2,"is_corresponding":false},{"id":331325,"name":"Paula Tanabe","orcid":"0000-0001-9933-6425","position":3,"is_corresponding":false},{"id":247061,"name":"Vimal K. Derebail","orcid":"0000-0002-7662-7497","position":4,"is_corresponding":false},{"id":449562,"name":"Marcus A. Carden","orcid":"0000-0003-3860-3619","position":0,"is_corresponding":true}],"reference_count":7,"raw_metadata":null,"created_at":"2026-07-19T02:10:43.302033Z","pmid":"39440574","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}