Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
-
Females as compared with males display better general health status, longevity, and improved clinical course after injury and infection. It is generally believed that the female advantage is associated with the effects of sex hormones. This review argues that the sex benefit of females during the host response is associated with polymorphism of X-linked genes and cellular mosaicism for X-linked parental alleles. ⋯ Several genes encoding key metabolic and regulatory proteins reside on the X chromosome, including members of the apoptotic cascade, hormone homeostasis, glucose metabolic enzymes, superoxide-producing machinery, and the toll-like receptor/nuclear factor kappaB/c-Jun N-terminal kinase signaling pathway. Polymorphic forms of these X-linked proteins are likely to manifest in phenotypic differences in the mosaic cell populations in females and may contribute to sex-related differences in the host response to injury and infection. The unique inheritance pattern of X-linked polymorphisms and their potential confounding effects in clinical trials are also discussed; furthermore, we present potential biomarkers for studying mosaic cell populations of innate immunity.
-
Severe traumatic brain injury (TBI) is characterized by a high mortality and poor outcome. The pathomechanisms involved are cytokine-mediated proinflammatory and anti-inflammatory reactions and significant cerebral microcirculatory disorders. The role of endothelin 1 (ET-1), a very potent vasoconstrictive peptide, in the deterioration of cerebral perfusion after trauma is still unclear. ⋯ Whereas plasma concentrations failed to reach significance, CSF values showed a significant peak on day 7 in both groups. The TBI-H patients had significantly (P < 0.05) higher values in the secondary peak compared with patients of the TBI group. The kinetics of traumatic SAH-dependent ET-1 needs to be assessed in further investigations.
-
Randomized Controlled Trial
A prospective randomized trial comparing oxygen delivery versus transcutaneous pressure of oxygen values as resuscitative goals.
Transcutaneous pressure of oxygen (PtcO2) correlates with arterial pressure of oxygen (PaO2) in nonshock states, but in shock states, PtcO2 approximates cardiac output with no response to increasing fraction of inspired oxygen (FiO2) and PaO2. An incremental change of more than 21 mmHg in PtcO2 in response to an FiO2 of 1.0 (identified as the oxygen challenge test [OCT]) implies adequate tissue perfusion, and lack of response has been associated with mortality. Patients with severe sepsis and septic shock requiring pulmonary artery catheters were randomized to two groups: the oxygen delivery (DO2) group was treated to a DO2 and mixed venous oxygen saturation goals, and the PtcO2 group was treated to achieve an OCT value of 40 mmHg or more. ⋯ The area under the receiver operating curve was 0.824 for the OCT at T24. The best OCT value was 25 mmHg at T24 with positive and negative predictive values of 87% and 90%, respectively. Treating patients with severe sepsis/septic shock to an OCT value of 25 mmHg or more may provide a specific end point of resuscitation that may be associated with better survival than resuscitating to the central hemodynamic parameters of DO2 and mixed venous oxygen saturation.
-
Outcomes after mild or moderate head trauma are worsened with associated hypotension, and secondary brain injury can be reduced with timely resuscitation. This study was performed to investigate HBOC-201 as a resuscitation therapy in a combined hemorrhagic shock and brain injury model. Anesthetized rats sustained moderate brain injury using a controlled cortical impact device, followed by rapid hemorrhage to a mean arterial pressure of 30 mmHg. ⋯ The contusion volume for HBOC (45.1 mm3) and SB (35.1 mm3) was less than LR (63.5 mm3, P < 0.01). Although CBF was diminished after resuscitation in the HBOC group, HBOC-treated animals maintained CVH and experienced significantly smaller contusion volume than those treated with LR. These results suggest that resuscitation with HBOC-201 protects autoregulatory mechanisms and may reduce secondary brain injury in traumatic brain injury.