Multi-institutional analysis of neutrophil-to-lymphocyte ratio (NLR) in patients with severe hemorrhage: A new mortality predictor value.

BACKGROUND: The neutrophil/lymphocyte ratio (NLR) has been associated as a predictor for increased mortality in critically ill patients. We sought to determine the relationship between NLR and outcomes in adult trauma patients with severe hemorrhage requiring the initiation of massive transfusion protocol (MTP). We hypothesized that the NLR would be a prognostic indicator of mortality in this population. METHODS: This was a multi-institutional retrospective cohort study of adult trauma patients (≥18 years) with severe hemorrhage who received MTP between November 2014 and November 2015. Differentiated blood cell counts obtained at days 3 and 10 were used to obtain NLR. Receiver operating characteristic (ROC) curve analysis assessed the predictive capacity of NLR on mortality. To identify the effect of NLR on survival, Kaplan-Meier (KM) survival analysis and Cox regression models were used. RESULTS: A total of 285 patients with severe hemorrhage managed with MTP were analyzed from six participating institutions. Most (80%) were men, 57.2% suffered blunt trauma. Median (IQR) age, Injury Severity Score, and Glasgow Coma Scale were 35 (25-47), 25 (16-36), and 9 (3-15), respectively. Using ROC curve analysis, optimal NLR cutoff values of 8.81 at day 3 and 13.68 at day 10 were calculated by maximizing the Youden index. KM curves at day 3 (p = 0.05) and day 10 (p = 0.02) revealed an NLR greater than or equal to these cutoff values as a marker for increased in-hospital mortality. Cox regression models failed to demonstrate an NLR over 8.81 as predictive of in-hospital mortality at day 3 (p = 0.056) but was predictive for mortality if NLR was greater than 13.68 at day 10 (p = 0.036). CONCLUSIONS: NLR is strongly associated with early mortality in patients with severe hemorrhage managed with MTP. Further research is needed to focus on factors that can ameliorate NLR in this patient population. LEVEL OF EVIDENCE: Prognostic study, level III.

Diluting the benefits of hemostatic resuscitation: a multi-institutional analysis.

BACKGROUND: Although minimization of crystalloids is a widely adopted practice in the resuscitation of patients with severe hemorrhage, its direct impact on high-ratio resuscitation (HRR) outcomes has not been analyzed. We hypothesize that HRR patients will have worse outcomes from crystalloid use. METHODS: This was a 4-year retrospective multi-institutional analysis (MIA) of patients who received massive transfusion protocol (MTP) managed with damage-control laparotomy. Ratios of fresh frozen plasma-packed red blood cell (PRBC) were calculated and divided in two groups: HRR (1-1:2) and low-ratio resuscitation (LRR < 1:2). Major outcome of interest was to analyze the direct impact of 24-hour crystalloid volume on HRR MTP patients who received 10 or more units of PRBC. Statistical analysis included analysis of variance, Fisher's exact, Kaplan-Meier (KM) survival curves, and multiple logistic regression. RESULTS: Total of five Level I trauma centers participated with 451 patients who received MTP with 10 or more units of PRBC (fresh frozen plasma/PRBC ratios, n = 365 (80.9%) HRR vs. n = 86 (19.0%) LRR. Overall 24-hour KM survival for the HRR versus LRR was 85.2% versus 68.6% (p = 0.0004). The volume of crystalloids on KM survival curve in HRR MTP patients was not significant for mortality (p = 0.52). Morbidity odds ratios (95% confidence interval) for complications were not significant for HRR but were for crystalloids: bacteremia, 1.05 (1.0-1.1); adult respiratory distress syndrome, 1.13 (1.0-1.2), and acute renal failure, 1.05 (1.0-1.1). CONCLUSION: Our MIA results support previous studies with decreased mortality in HRR group when compared with LRR. This is the first MIA to demonstrate increased morbidity from crystalloid use in HRR. Within all MTPs with 10 or more units of PRBC, HRR was not a predictor of morbidity, but crystalloid volume was. Caution in overzealous use of crystalloid during HRR is warranted. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Restrictive fluid resuscitation in combination with damage control resuscitation: time for adaptation.

BACKGROUND: Damage control resuscitation (DCR) conveys a survival advantage in patients with severe hemorrhage. The role of restrictive fluid resuscitation (RFR) when used in combination with DCR has not been elucidated. We hypothesize that RFR, when used with DCR, conveys an overall survival benefit for patients with severe hemorrhage. METHODS: This is a retrospective analysis from January 2007 to May 2011 at a Level I trauma center. Inclusion criteria included penetrating torso injuries, systolic blood pressure less than or equal to 90 mm Hg, and managed with DCR and damage control surgery (DCS). There were two groups according to the quantity of fluid before DCS: (1) standard fluid resuscitation (SFR) greater than or equal to 150 mL of crystalloid; (2) RFR less than 150 mL of crystalloid. Demographics and outcomes were analyzed. RESULTS: Three hundred seven patients were included. Before DCS, 132 (43%) received less than 150 mL of crystalloids, grouped under RFR; and 175 (57%) received greater than or equal to 150 mL of crystalloids, grouped under SFR. Demographics and initial clinical characteristics were similar between the study groups. Compared with the SFR group, RFR patients received less fluid preoperatively (129 mL vs. 2,757 mL; p < 0.001), exhibited a lower intraoperative mortality (9% vs. 32%; p < 0.001), and had a shorter hospital length of stay (13 vs. 18 days; p = 0.02). Patients in the SFR group had a lower trauma intensive care unit mortality (5 vs. 12%; p = 0.03) but exhibited a higher overall mortality. Patients receiving RFR demonstrated a survival benefit, with an odds ratio for mortality of 0.69 (95% confidence interval, 0.37-0.91). CONCLUSION: To the best of our knowledge, this is the first civilian study that analyzes the impact of RFR in patients managed with DCR. Its use in conjunction with DCR for hypotensive trauma patients with penetrating injuries to the torso conveys an overall and early intraoperative survival benefit. LEVEL OF EVIDENCE: Therapeutic study, level IV.