Association Between Time to Source Control in Sepsis and 90-Day Mortality.

Importance: Rapid source control is recommended to improve patient outcomes in sepsis. Yet there are few data to guide how rapidly source control is required. Objective: To determine the association between time to source control and patient outcomes in community-acquired sepsis. Design, Setting, and Particpants: Multihospital integrated health care system cohort study of hospitalized adults (January 1, 2013, to December 31, 2017) with community-acquired sepsis as defined by Sepsis-3 who underwent source control procedures. Follow-up continued through January 1, 2019, and data analyses were completed March 17, 2022. Exposures: Early (<6 hours) compared with late (6-36 hours) source control as well as each hour of source control delay (1-36 hours) from sepsis onset. Main Outcomes and Measures: Multivariable models were clustered at the level of hospital with adjustment for patient factors, sepsis severity, resource availability, and the physiologic stress of procedures generating adjusted odds ratios (aOR) and 95% CI. Results: Of 4962 patients with sepsis (mean [SD] age, 62 [16] years; 52% male; 85% White; mean [SD] Sequential Organ Failure Assessment score, 3.8 [2.5]), source control occurred at a median (IQR) of 15.4 hours (5.5-21.7) after sepsis onset, with 1315 patients (27%) undergoing source control within 6 hours. The crude 90-day mortality was similar for early and late source control (n = 177 [14%] vs n = 529 [15%]; P = .35). In multivariable models, early source control was associated with decreased risk-adjusted odds of 90-day mortality (aOR, 0.71; 95% CI, 0.63-0.80). This association was greater among gastrointestinal and abdominal (aOR, 0.56; 95% CI, 0.43-0.80) and soft tissue interventions (aOR, 0.72; 95% CI, 0.55-0.95) compared with orthopedic and cranial interventions (aOR, 1.33; 95% CI, 0.96-1.83; P < .001 for interaction). Conclusions and Relevance: Source control within 6 hours of community-acquired sepsis onset was associated with a reduced risk-adjusted odds of 90-day mortality. Prioritizing the rapid identification of septic foci and initiation of source control interventions can reduce the number of avoidable deaths among patients with sepsis.

Forgot calcium? Admission ionized-calcium in two civilian randomized controlled trials of prehospital plasma for traumatic hemorrhagic shock.

BACKGROUND: Randomized clinical trials (RCTs) support the use of prehospital plasma in traumatic hemorrhagic shock, especially in long transports. The citrate added to plasma binds with calcium, yet most prehospital trauma protocols have no guidelines for calcium replacement. We reviewed the experience of two recent prehospital plasma RCTs regarding admission ionized-calcium (i-Ca) blood levels and its impact on survival. We hypothesized that prehospital plasma is associated with hypocalcemia, which in turn is associated with lower survival. METHODS: We studied patients enrolled in two institutions participating in prehospital plasma RCTs (control, standard of care; experimental, plasma), with i-Ca collected before calcium supplementation. Adults with traumatic hemorrhagic shock (systolic blood pressure ≤70 mm Hg or 71-90 mm Hg + heart rate ≥108 bpm) were eligible. We use generalized linear mixed models with random intercepts and Cox proportional hazards models with robust standard errors to account for clustered data by institution. Hypocalcemia was defined as i-Ca of 1.0 mmol/L or less. RESULTS: Of 160 subjects (76% men), 48% received prehospital plasma (median age, 40 years [interquartile range, 28-53 years]) and 71% suffered blunt trauma (median Injury Severity Score [ISS], 22 [interquartile range, 17-34]). Prehospital plasma and control patients were similar regarding age, sex, ISS, blunt mechanism, and brain injury. Prehospital plasma recipients had significantly higher rates of hypocalcemia compared with controls (53% vs. 36%; adjusted relative risk, 1.48; 95% confidence interval [CI], 1.03-2.12; p = 0.03). Severe hypocalcemia was significantly associated with decreased survival (adjusted hazard ratio, 1.07; 95% CI, 1.02-1.13; p = 0.01) and massive transfusion (adjusted relative risk, 2.70; 95% CI, 1.13-6.46; p = 0.03), after adjustment for confounders (randomization group, age, ISS, and shock index). CONCLUSION: Prehospital plasma in civilian trauma is associated with hypocalcemia, which in turn predicts lower survival and massive transfusion. These data underscore the need for explicit calcium supplementation guidelines in prehospital hemotherapy. LEVEL OF EVIDENCE: Therapeutic, level II.