Balancing enrollment and mortality in hemorrhage control trials: A secondary analysis of the PROPPR trial.

BACKGROUND: Designing clinical trials on hemorrhage control requires carefully balancing the need for high enrollment numbers with the need of focusing on the sickest patients. The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial enrolled patients within 2 hours of arrival to the emergency department for a trial of injured patients at risk for massive transfusion. We conducted a secondary analysis to determine how time-to-randomization affected patient outcomes and the balance between enrollment and mortality. METHODS: Patients from the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial were compared based on 30-minute time to randomization intervals. Outcomes included 24-hour and 30-day mortality, time to hemostasis, adverse events, and operative procedures. Additional analyses were conducted based on treatment arm allocation, mechanism of injury, and variation in start time (arrival vs. randomization). RESULTS: Randomization within 30 minutes of arrival was associated with higher injury severity (median Injury Severity Score, 29 vs. 26 overall; p < 0.01), lower systolic blood pressure (median, 91 vs. 102 mm Hg overall; p < 0.01), and increased penetrating mechanism (50% vs. 47% overall; p < 0.01). Faster time-to-randomization was associated with increased 24-hour (20% for 0- to 30 minute entry, 9% for 31-minute to 60-minute entry, 10% for 61-minute to 90-minute entry, 0% for 91-minute to 120-minute entry; p < 0.01) and 30-day mortality (p < 0.01). There were no significant associations between time-to-randomization and adverse event occurrence, operative interventions, or time to hemostasis. CONCLUSION: Increasing time to randomization in this large multicenter randomized trial was associated with increased survival. Fastest randomization (within 0-30 minutes) was associated with highest 24-hour and 30-day mortality, but only 57% of patients were enrolled within this timeframe. Only 3% of patients were enrolled within the last 30-minute window (91-120 minutes), with none of them dying within the first 24 hours. For a more optimal balance between enrollment and mortality, investigators should consider shortening the time to randomization when planning future clinical trials of hemorrhage control interventions. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level II.

Vascular complications based on mode of extracorporeal membrane oxygenation.

BACKGROUND: Vascular complications remain a prevalent and devastating complication of extracorporeal membrane oxygenation (ECMO). Risks for vascular complications have risen as the volume and medical complexity of ECMO cases has rapidly increased in recent years. This study assesses occurrence and clinical impact of vascular complications across all ECMO modes and cannulation methods in a high-volume academic center. METHODS: A retrospective single-institution review was performed of all ECMO cannulations for central or peripheral venovenous (VV) or venoarterial (VA) ECMO in 2019-2020. Patients who expired during cannulation were excluded. Primary outcomes of vascular consultation rates at or after ECMO placement, limb loss, and mortality were assessed during index hospitalization. RESULTS: A total of 229 patients were identified during the 2-year study period. VA ECMO was used in the majority of patients (n = 137, 60%), with 83% (N = 114) undergoing peripheral cannulation. Vascular surgery was consulted in 54 (23.6%) patients. Complication rates ranged from 33.9% in peripheral VA cannulation to 7% in jugular VV cannulation. Overall, 65% of vascular consults required operative intervention; interventions were highest in peripheral VA ECMO (n = 30 of 114, 26.3%). Across all ECMO types, acute limb ischemia (ALI) was the most common complication (n = 38, 16.5%), with rates ranging from 26.1% in central VA ECMO to 4.8% in jugular VV ECMO. Distal antegrade perfusion catheters (DPCs) were employed in n = 68 of 114 (59.6%) of all peripheral VA ECMO cases. Prophylactic DPCs were found to be incorrectly placed in 10.2% (n = 7 of 68) of cases, which obscured the ability to fully evaluate the effect of prophylactic DPCs on reducing rates of ALI. Major amputation (Below Knee Amputation/Above Knee Amputation) occurred in six peripheral VA patients (5.3%), two central VA patients (8.65), and two femoral-femoral VV patients (4%). Patients with ALI experienced significantly lower rates of in-hospital survival in Kaplan-Meier analysis (32.5% vs 54%, log-rank = 0.023). CONCLUSIONS: This study highlights the prevalence of vascular complications, and their associated mortality impact, across all modes of ECMO and additionally identifies several areas for institutional performance improvement. ALI was the most common complication across all cohorts and was associated with decreased in-hospital survival. The impact of DPC on ALI was difficult to elucidate due to nonstandardized placement patterns and selective use. In the care of these medically complex patients on multidisciplinary teams, review of outcomes and group discussions targeting areas for improvement are critical to success; in this study, findings resulted in the development of a lower extremity perfusion management protocol.

Care for Chiari malformation type I: the role of socioeconomic disadvantage and race.

OBJECTIVE: There is little research on the effect of social determinants of health on Chiari malformation type I (CM-I). The authors analyzed data on all children evaluated for CM-I at a single institution to assess how socioeconomic factors and race affect the surgical treatment of this population. METHODS: Medical records of patients treated for CM-I at the authors' institution between 1992 and 2017 were reviewed. Area Deprivation Index (ADI) and Rural-Urban Commuting Area (RUCA) codes for each patient were used to measure neighborhood disadvantage. Non-Hispanic White patients were compared to non-White patients and Hispanic patients of any race (grouped together as non-White in this study) in terms of insurance status, ADI, and RUCA. Patients with initially benign CM-I, defined as not having undergone surgery within 9 months of their initial visit, were then stratified by having delayed symptom presentation or not, and compared on these same measures. RESULTS: The sample included 665 patients with CM-I: 82% non-Hispanic White and 18% non-White. The non-White patients were more likely to reside in disadvantaged (OR 3.4, p < 0.001) and urban (OR 4.66, p < 0.001) neighborhoods and to have public health insurance (OR 3.11, p < 0.001). More than one-quarter (29%) of patients underwent surgery. The non-White and non-Hispanic White patients had similar surgery rates (29.5% vs 28.9%, p = 0.895) at similar ages (8.8 vs 9.7 years, p = 0.406). There were no differences by race/ethnicity for symptoms at presentation. Surgical and nonsurgical patients had similar ADI scores (3.9 vs 4.2, p = 0.194), RUCA scores (2.1 vs 2.3, p = 0.252), and private health insurance rates (73.6% vs 74.2%, p = 0.878). A total of 153 patients underwent surgery within 9 months of their initial visit. The remaining 512 were deemed to have benign CM-I. Of these, 40 (7.8%) underwent decompression surgery for delayed symptom presentation. Patients with delayed symptom presentation were from less disadvantaged (ADI 3.2 vs 4.2; p = 0.025) and less rural (RUCA 1.8 vs 2.3; p = 0.023) areas than those who never underwent surgery. CONCLUSIONS: Although non-White patients were more likely to be socioeconomically disadvantaged, race and socioeconomic disadvantage were not associated with undergoing surgical treatment. However, among patients with benign CM-I, those undergoing decompression for delayed symptom presentation resided in more affluent and urban areas.