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Prehospital resuscitation with hypertonic saline-dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients.

ABSTRACT: Traumatic brain injury (TBI) initiates interrelated inflammatory and coagulation cascades characterized by wide-spread cellular activation, induction of leukocyte and endothelial cell adhesion molecules and release of soluble pro/antiinflammatory cytokines and thrombotic mediators. Resuscitative care is focused on optimizing cerebral perfusion and reducing secondary injury processes. Hypertonic saline is an effective osmotherapeutic agent for the treatment of intracranial hypertension and has immunomodulatory properties that may confer neuroprotection. This study examined the impact of hypertonic fluids on inflammatory/coagulation cascades in isolated head injury.Using a prospective, randomized controlled trial we investigated the impact of prehospital resuscitation of severe TBI (GCS < 8) patients using 7.5% hypertonic saline in combination with 6% dextran-70 (HSD) vs 0.9% normal saline (NS), on selected cellular and soluble inflammatory/coagulation markers. Serial blood samples were drawn from 65 patients (30 HSD, 35 NS) at the time of hospital admission and at 12, 24, and 48-h post-resuscitation. Flow cytometry was used to analyze leukocyte cell-surface adhesion (CD62L, CD11b) and degranulation (CD63, CD66b) molecules. Circulating concentrations of soluble (s)L- and sE-selectins (sL-, sE-selectins), vascular and intercellular adhesion molecules (sVCAM-1, sICAM-1), pro/antiinflammatory cytokines [tumor necrosis factor (TNF)-alpha and interleukin (IL-10)], tissue factor (sTF), thrombomodulin (sTM) and D-dimers (D-D) were assessed by enzyme immunoassay. Twenty-five healthy subjects were studied as a control group.TBI provoked marked alterations in a majority of the inflammatory/coagulation markers assessed in all patients. Relative to control, NS patients showed up to a 2-fold higher surface expression of CD62L, CD11b and CD66b on polymorphonuclear neutrophils (PMNs) and monocytes that persisted for 48-h. HSD blunted the expression of these cell-surface activation/adhesion molecules at all time-points to levels approaching control values. Admission concentrations of endothelial-derived sVCAM-1 and sE-selectin were generally reduced in HSD patients. Circulating sL-selectin levels were significantly elevated at 12 and 48, but not 24 h post-resuscitation with HSD. TNF-alpha and IL-10 levels were elevated above control throughout the study period in all patients, but were reduced in HSD patients. Plasma sTF and D-D levels were also significantly lower in HSD patients, whereas sTM levels remained at control levels.These findings support an important modulatory role of HSD resuscitation in attenuating the upregulation of leukocyte/endothelial cell proinflammatory/prothrombotic mediators, which may help ameliorate secondary brain injury after TBI.NCT00878631.

SUBMITTER: Rhind SG

PROVIDER: S-EPMC2819256 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Prehospital resuscitation with hypertonic saline-dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients.

Rhind Shawn G SG Crnko Naomi T NT Baker Andrew J AJ Morrison Laurie J LJ Shek Pang N PN Scarpelini Sandro S Rizoli Sandro B SB

Journal of neuroinflammation 20100118

<h4>Background</h4>Traumatic brain injury (TBI) initiates interrelated inflammatory and coagulation cascades characterized by wide-spread cellular activation, induction of leukocyte and endothelial cell adhesion molecules and release of soluble pro/antiinflammatory cytokines and thrombotic mediators. Resuscitative care is focused on optimizing cerebral perfusion and reducing secondary injury processes. Hypertonic saline is an effective osmotherapeutic agent for the treatment of intracranial hype ...[more]

PMID: 20082712

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Project description:To investigate the effect of the occurrence of early hyperchloremia on death or severe disability at 180 days in patients with severe traumatic brain injury (TBI).DesignPost hoc analysis of Resuscitation Outcomes Consortium Hypertonic Saline (ROC HS)-TBI trial.SettingA total of 114 North American emergency medical services agencies in the ROC.PatientsA total of 991 patients with severe TBI and Glasgow Coma Scale score of less than or equal to 8.InterventionsPrehospital resuscitation with single IV dose (250 cc) of 7.5% saline in 6% dextran-70, 7.5% saline (no dextran), or crystalloid.Measurements and main resultsPatients with increased serum chloride concentrations (110 mmol/L or greater) 24 hours after randomization were identified. Hyperchloremia was graded into one or greater than or equal to 2 occurrences in the first 24 hours. Logistic regression analyses were performed to determine the effects of hyperchloremia on: 1) death or severe disability at 180 days and 2) death within 180 days after adjusting for confounders. Compared with patients without hyperchloremia, patients with greater than or equal to 2 occurrences of hyperchloremia had significantly higher odds of death or severe disability at 180 days (odds ratio [OR], 1.81; 95% CI, 1.19-2.75) and death within 180 days (OR, 1.89; 95% CI, 1.14-3.08) after adjustment for confounders. However, the total volume of fluids administered during the first 24 hours was an independent predictor of death within 180 days; therefore, after adding an interaction term between the total volume of fluids administered during the first 24 hours and greater than or equal to 2 occurrences of hyperchloremia, patients with greater than or equal to 2 occurrences of hyperchloremia had significantly higher odds of death within 180 days (OR, 2.35; 95% CI, 1.21-4.61 d) but not of composite outcome of death or severe disability at 180 days.ConclusionsAfter modifying for the effect of the total volume of fluids administered during the first 24 hours, multiple occurrences of hyperchloremia in the first 24 hours were associated with higher odds of death within 180 days in patients with severe TBI.

Project description:BackgroundOur objective was to establish the safety of 3% hypertonic saline (HTS) resuscitation for trauma and acute care surgery patients undergoing emergent laparotomy and temporary abdominal closure (TAC) with the hypothesis that HTS administration would be associated with hyperosmolar hypercholoremic acidosis, lower resuscitation volumes, and higher fascial closure rates, without adversely affecting renal function.MethodsWe performed a retrospective cohort analysis of 189 trauma and acute care surgery patients who underwent emergent laparotomy and TAC, comparing patients with normal baseline renal function who received 3% HTS at 30 mL/h (n = 36) to patients with standard resuscitation (n = 153) by baseline characteristics, resuscitation parameters, and outcomes including primary fascial closure and Kidney Disease: Improving Global Outcomes stages of acute kidney injury.ResultsThe HTS and standard resuscitation groups had similar baseline illness severity and organ dysfunction, though HTS patients had lower serum creatinine at initial laparotomy (1.2 mg/dL vs. 1.4 mg/dL; p = 0.078). Forty-eight hours after TAC, HTS patients had significantly higher serum sodium (145.8 mEq/L vs. 142.2 mEq/L, p < 0.001), chloride (111.8 mEq/L vs. 106.6 mEq/L, p < 0.001), and osmolarity (305.8 mOsm/kg vs. 299.4 mOsm/kg; p = 0.006), and significantly lower arterial pH (7.34 vs. 7.38; p = 0.011). The HTS patients had lower intravenous fluid (IVF) volumes within 48 hours of TAC (8.5 L vs. 11.8 L; p = 0.004). Serum creatinine, urine output, and kidney injury were similar between groups. Fascial closure was achieved for 92% of all HTS patients and 77% of all standard resuscitation patients (p = 0.063). Considering all 189 patients, higher IVF resuscitation volumes within 48 hours of TAC were associated with decreased odds of fascial closure (odds ratio, 0.90; 95% confidence interval, 0.83-0.97; p = 0.003).ConclusionHypertonic saline resuscitation was associated with the development of a hypernatremic, hyperchloremic, hyperosmolar acidosis, and lower total IVF resuscitation volumes, without adversely affecting renal function. These findings may not be generalizable to patients with baseline renal dysfunction and susceptibility to hyperchloremic acidosis-induced kidney injury.Level of evidencePrognostic study, level II.

Project description:BackgroundIntracranial pressure control has long been recognized as an important requirement for patients with severe traumatic brain injury. Hypertonic saline has drawn attention as an alternative to mannitol in this setting. The aim of this study was to assess the effects of hypertonic saline versus mannitol on clinical outcomes in patients with traumatic brain injury in prehospital, emergency department, and intensive care unit settings by systematically reviewing the literature and synthesizing the evidence from randomized controlled trials.MethodsWe searched the MEDLINE database, the Cochrane Central Register of Controlled Trials, and the Igaku Chuo Zasshi (ICHUSHI) Web database with no date restrictions. We selected randomized controlled trials in which the clinical outcomes of adult patients with traumatic brain injury were compared between hypertonic saline and mannitol strategies. Two investigators independently screened the search results and conducted the data extraction. The primary outcome was all-cause mortality. The secondary outcomes were 90-day and 180-day mortality, good neurological outcomes, reduction in intracranial pressure, and serum sodium level. Random effects estimators with weights calculated by the inverse variance method were used to determine the pooled risk ratios.ResultsA total of 125 patients from four randomized trials were included, and all the studies were conducted in the intensive care unit. Among 105 patients from three trials that evaluated the primary outcome, 50 patients were assigned to the hypertonic saline group and 55 patients were assigned to the mannitol group. During the observation period, death was observed for 16 patients in the hypertonic saline group (32.0%) and 21 patients in the mannitol group (38.2%). The risks were not significant between the two infusion strategies (pooled risk ratio, 0.82; 95% confidence interval, 0.49-1.37). There were also no significant differences between the two groups in the other secondary outcomes. However, the certainty of the evidence was rated very low for all outcomes.ConclusionsOur findings revealed no significant difference in the all-cause mortality rates between patients receiving hypertonic saline or mannitol to control intracranial pressure. Further investigation is warranted because we only included a limited number of studies.

Project description:ContextHypertonic fluids restore cerebral perfusion with reduced cerebral edema and modulate inflammatory response to reduce subsequent neuronal injury and thus have potential benefit in resuscitation of patients with traumatic brain injury (TBI).ObjectiveTo determine whether out-of-hospital administration of hypertonic fluids improves neurologic outcome following severe TBI.Design, setting, and participantsMulticenter, double-blind, randomized, placebo-controlled clinical trial involving 114 North American emergency medical services agencies within the Resuscitation Outcomes Consortium, conducted between May 2006 and May 2009 among patients 15 years or older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less who did not meet criteria for hypovolemic shock. Planned enrollment was 2122 patients.InterventionA single 250-mL bolus of 7.5% saline/6% dextran 70 (hypertonic saline/dextran), 7.5% saline (hypertonic saline), or 0.9% saline (normal saline) initiated in the out-of-hospital setting.Main outcome measureSix-month neurologic outcome based on the Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or ≤4).ResultsThe study was terminated by the data and safety monitoring board after randomization of 1331 patients, having met prespecified futility criteria. Among the 1282 patients enrolled, 6-month outcomes data were available for 1087 (85%). Baseline characteristics of the groups were equivalent. There was no difference in 6-month neurologic outcome among groups with regard to proportions of patients with severe TBI (GOSE ≤4) (hypertonic saline/dextran vs normal saline: 53.7% vs 51.5%; difference, 2.2% [95% CI, -4.5% to 9.0%]; hypertonic saline vs normal saline: 54.3% vs 51.5%; difference, 2.9% [95% CI, -4.0% to 9.7%]; P = .67). There were no statistically significant differences in distribution of GOSE category or Disability Rating Score by treatment group. Survival at 28 days was 74.3% with hypertonic saline/dextran, 75.7% with hypertonic saline, and 75.1% with normal saline (P = .88).ConclusionAmong patients with severe TBI not in hypovolemic shock, initial resuscitation with either hypertonic saline or hypertonic saline/dextran, compared with normal saline, did not result in superior 6-month neurologic outcome or survival.Trial registrationclinicaltrials.gov Identifier: NCT00316004.

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Prehospital resuscitation with hypertonic saline-dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients.

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Prehospital resuscitation with hypertonic saline-dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients.

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