Improvement of Blood-Brain Barrier Integrity in Traumatic Brain Injury and Hemorrhagic Shock Following Treatment With Valproic Acid and Fresh Frozen Plasma. (Lima)

Nikolian VC, et al. Improvement of Blood-Brain Barrier Integrity in Traumatic Brain Injury and Hemorrhagic Shock Following Treatment With Valproic Acid and Fresh Frozen Plasma. Crit Care Med. 2018 Jan; 46(1):e59-e66.

OBJECTIVE: Combined traumatic brain injury and hemorrhagic shock are highly lethal. Following injuries, the integrity of the blood-brain barrier can be impaired, contributing to secondary brain insults. The status of the blood-brain barrier represents a potential factor impacting long-term neurologic outcomes in combined injuries. Treatment strategies involving plasma-based resuscitation and valproic acid therapy have shown efficacy in this setting. We hypothesize that a component of this beneficial effect is related to blood-brain barrier preservation.

Continue reading

Impact of Source Control in Patients With Severe Sepsis and Septic Shock. (Betters)

Martínez ML, et al. Impact of Source Control in Patients With Severe Sepsis and Septic Shock. Crit Care Med. 2017 Jan;45(1):11-19.

OBJECTIVES: Time to clearance of pathogens is probably critical to outcome in septic shock. Current guidelines recommend intervention for source control within 12 hours after diagnosis. We aimed to determine the epidemiology of source control in the management of sepsis and to analyze the impact of timing to source control on mortality.

DESIGN: Prospective observational analysis of the Antibiotic Intervention in Severe Sepsis study, a Spanish national multicenter educational intervention to improve antibiotherapy in sepsis.

SETTING: Ninety-nine medical-surgical ICUs in Spain.

PATIENTS: We enrolled 3,663 patients with severe sepsis or septic shock during three 4-month periods between 2011 and 2013.

INTERVENTIONS: Source control and hospital mortality.

MEASUREMENTS AND MAIN RESULTS: A total of 1,173 patients (32%) underwent source control, predominantly for abdominal, urinary, and soft-tissue infections. Compared with patients who did not require source control, patients who underwent source control were older, with a greater prevalence of shock, major organ dysfunction, bacteremia, inflammatory markers, and lactic acidemia. In addition, compliance with the resuscitation bundle was worse in those undergoing source control. In patients who underwent source control, crude ICU mortality was lower (21.2% vs 25.1%; p = 0.010); after adjustment for confounding factors, hospital mortality was also lower (odds ratio, 0.809 [95% CI, 0.658-0.994]; p = 0.044). In this observational database analysis, source control after 12 hours was not associated with higher mortality (27.6% vs 26.8%; p = 0.789).

CONCLUSIONS: Despite greater severity and worse compliance with resuscitation bundles, mortality was lower in septic patients who underwent source control than in those who did not. The time to source control could not be linked to survival in this observational database.

Association of presence and timing of invasive airway placement with outcomes after pediatric in-hospital cardiac arrest. (Emrath)

Gupta P, Rettiganti M, Gossett JM, et al. Association of presence and timing of invasive airway placement with outcomes after pediatric in-hospital cardiac arrest. Resuscitation. 2015 Jul;92:53-8.

Full-text for Emory users.

BACKGROUND: Little data exist regarding the association of presence of an invasive airway before cardiac arrest or early placement of an invasive airway after cardiac arrest with outcomes in children who experience in-hospital cardiac arrest.

METHODS: We conducted a retrospective review of patients aged 1 day to 18 years who received cardiopulmonary resuscitation (CPR) for ≥ 1 min in any of the three intensive care units (ICUs) at a tertiary care, academic children’s hospital between 2002 and 2010. Specific outcomes evaluated included survival to hospital discharge, return of spontaneous circulation (ROSC), 24-h survival, and good neurological status at hospital discharge. We fitted multivariable logistic regression models to evaluate the association between the presence of an invasive airway prior to cardiac arrest and timing of placement of an invasive airway with these outcomes.

RESULTS: Three hundred and ninety-one patients were included. Of these, 197 (51%) patients were already tracheally intubated before the occurrence of cardiac arrest. Median time to intubation was 6 min [interquartile range (IQR): 2, 12] among the 194 patients tracheally intubated following cardiac arrest. We found lower survival to hospital discharge among patients intubated prior to cardiac arrest (intubated vs. non-intubated group, 43% vs. 61%, p < 0.001). After adjusting for patient and event characteristics, presence of an invasive airway prior to cardiac arrest was not associated with a significant improvement in survival to hospital discharge [odds ratio (OR): 0.70, 95% confidence interval (CI): 0.42-1.16, p = 0.17], or good neurological outcomes (OR: 0.60, 95% CI: 0.34-1.05, p = 0.07). Similarly, early placement of an invasive airway after cardiac arrest was also not associated with an improvement in survival to hospital discharge (OR: 1.05, 95% CI: 0.78-1.42, p = 0.73), or good neurological outcomes (OR: 1.08, 95% CI: 0.77-1.53, p = 0.65).

CONCLUSIONS: Our study demonstrates that presence of an invasive airway prior to cardiac arrest or early placement of an invasive airway after cardiac arrest is not associated with an improvement in survival to hospital discharge or good neurological outcomes. Further study of the relationship between invasive airway management and survival following cardiac arrest is warranted.

Randomized controlled trial of inhaled nitric oxide for the treatment of microcirculatory dysfunction in patients with sepsis. (Dugan)

Trzeciak S, Glaspey LJ, Dellinger RP, et al. Randomized controlled trial of inhaled nitric oxide for the treatment of microcirculatory dysfunction in patients with sepsis*. Crit Care Med. 2014 Dec;42(12):2482-92.

Full-text for Children’s and Emory users.

OBJECTIVES: Sepsis treatment guidelines recommend macrocirculatory hemodynamic optimization; however, microcirculatory dysfunction is integral to sepsis pathogenesis. We aimed to test the hypothesis that following macrocirculatory optimization, inhaled nitric oxide would improve microcirculation in patients with sepsis and that improved microcirculation would improve lactate clearance and multiple organ dysfunction.

DESIGN: Randomized, sham-controlled clinical trial.

SETTING: Single urban academic medical center.

PATIENTS: Adult patients with severe sepsis and systolic blood pressure less than 90 mm Hg despite intravascular volume expansion and/or serum lactate greater than or equal to 4.0 mmol/L.

INTERVENTIONS: After achievement of macrocirculatory resuscitation goals, we randomized patients to 6 hours of inhaled nitric oxide (40 ppm) or sham inhaled nitric oxide administration. We administered study drug via a specialized delivery device that concealed treatment allocation so that investigators and clinical staff remained blinded.

MEASUREMENTS AND MAIN RESULTS: We performed sidestream dark-field videomicroscopy of the sublingual microcirculation prior to and 2 hours after study drug initiation. The primary outcome measure was the change in microcirculatory flow index. Secondary outcomes were lactate clearance and change in Sequential Organ Failure Assessment score. We enrolled 50 patients (28 of 50 [56%] requiring vasopressor agents; 15 of 50 [30%] died). Although inhaled nitric oxide significantly raised plasma nitrite levels, it did not improve microcirculatory flow, lactate clearance, or organ dysfunction. In contrast to previous studies conducted during the earliest phase of resuscitation, we found no association between changes in microcirculatory flow and lactate clearance or organ dysfunction.

CONCLUSIONS: Following macrocirculatory optimization, inhaled nitric oxide at 40 ppm did not augment microcirculatory perfusion in patients with sepsis. Further, we found no association between microcirculatory perfusion and multiple organ dysfunction after initial resuscitation.