Transport time after combat-related injury and patient-reported outcomes among US service members.

INTRODUCTION: The 'golden hour' is a universal paradigm that suggests trauma patients have lower morbidity and mortality when provided with medical care within 1 hour after injury. The objective of this study was to examine whether transport time from point of injury to a military treatment facility (MTF) in-theatre was associated with patient-reported outcomes, such as post-traumatic stress disorder (PTSD), depression and quality of life (QOL), among US service members with combat-related injury. METHODS: Participants were injured between March 2003 and March 2016 and completed standardised assessments of PTSD, depression and QOL for theWounded Warrior Recovery Project (WWRP) between January 2013 and November 2017. Multivariable regressions were used to assess the relationship between transport time (≤1 hour or >1 hour from injury to MTF) and positive screens for PTSD and depression, and QOL, respectively.Overall, 45.6% of participants (n=879) arrived at an MTF within 1 hour postinjury. About 8 years passed between when participants were injured on deployment and when they completed their first WWRP assessment. Approximately 48% of participants screened positive for PTSD and 51.3% for depression, with a mean QOL score of 0.513 (SD=0.150). After adjusting for covariates, transport time was not significantly associated with PTSD (OR 1.04, 95% CI 0.79 to 1.38; p=0.77), depression (OR 0.92, 95% CI 0.69 to 1.21; p=0.55) or QOL (ß=0.009; p=0.38). CONCLUSION: Transport time was not associated with patient-reported outcomes among US service members with combat-related injury. These findings are important as we seek to understand how combat casualties may be affected by extended medical evacuation or transport times anticipated in future expeditionary operations.

Activation of the central vasopressin system: a potential factor in the etiology of hypertension.

Peptides containing the ACTH4-10 or gamma MSH3-9 sequence have varying degrees of natriuretic activity. Several of these peptides also possess pressor activity. The basis for the cardiovascular effect appears to be increased central sympathetic drive. The mechanism by which circulating gamma MSH affects central cardiovascular regulation is via an interaction with structures in the anteroventral third ventricle (AV3V) region, resulting in stimulation of the central vasopressin system. This pathway projects from the forebrain to hindbrain and spinal cord centers which regulate autonomic drive. We have extended these initial findings to other central sympathoexcitatory pressor factors, including hypertonic saline (HS) and angiotensin II (A-II). In both of these cases, the central vasopressin system mediates their autonomic effects. Since HS and A-II also work through the AV3V, the central vasopressin system may be partially responsible for the increased sympathetic drive noted in forms of hypertension which are AV3V-dependent.

Activation of the central vasopressin system: a common pathway for several centrally acting pressor agents.

Hypertonic saline (HS) and angiotensin II (ANG II) administered centrally or peripherally produce a forebrain-mediated central nervous system-(CNS) dependent pressor action. Although the majority of these effects are due to increased central sympathetic drive and inhibition of the cardiac baroreceptor reflex, evidence from peripheral infusions of vasopressin (Vp) receptor antagonists have suggested that part of the blood pressure increase may be due to circulating Vp. We now report that blockade of CNS Vp receptors in rats, via a fourth ventricle infusion of a Vp receptor antagonist, attenuated greater than 70% of the pressor response to lateral ventricle infusion of HS, ANG II, or hypertonic glucose (HG). Intravenous administration of the Vp antagonist could block only 40% of the HS response. When lateral ventricle infusion of HS was performed in rats with a hereditary lack of Vp (diabetes insipidic rats) no pressor response was obtained. Because centrally administered Vp has autonomic nervous system effects that are similar to those induced by HS or ANG II, our results suggest that CNS Vp may provide a link between forebrain acting pressor agents and autonomic nervous system regulation. Finally, HG produced a pressor effect that had an equivalent peak response to HS. However, unlike the HS response, the pressor effect to HG returned to base line within approximately 5 min during a 10-min infusion. Thus there appears to be a quantitative difference in the pressor responses produced by activation of sodium vs. osmoreceptors.

Central vasopressin system mediation of acute pressor effect of gamma-MSH.

Intravenous (iv) administration of gamma-melanocyte-stimulating hormone (gamma-MSH) produces central sympathetically mediated pressor and cardioaccelerator effects and increases the activity of hypothalamic vasopressinergic neurons. The autonomic actions are similar to infusion of vasopressin (Vp) into the hindbrain of 4th ventricle (Ven). To ascertain whether activation of the central Vp system is the proximate cause of the pressor effects of gamma-MSH, we investigated the effects of gamma-MSH in rats pre- and postblockade of central nervous system Vp receptors and in rats with a hereditary lack of vasopressin (Brattleboro strain). Central Vp receptor blockade significantly reduced (80%) the pressor effects of iv gamma-MSH. As a control, iv administration of the antagonist, while effective in blocking the pressor effect of iv Vp, had no effect on the gamma-MSH pressor response. When compared with their genetic controls (Long-Evans strain), Brattleboro rats also had greater than 80% reduction in their pressor response to iv gamma-MSH. The results indicate that circulating gamma-MSH activates the central Vp system to produce its sympathoexcitatory pressor effects.