Purpose of review As the elderly population expands and adopts increasingly more active lifestyles, trauma and critical care practitioners will be faced with providing care for greater numbers of severely injured patients. However, because of their associated preexisting medical conditions and poor relative physiologic reserve, geriatric patients have higher mortality rates and poorer long-term functional outcomes than their younger counterparts. A thorough understanding of the causes for these disparate outcomes is critical if successful strategies and treatments for this unique patient population are to be developed. Recent findings The currently available geriatric trauma literature is largely descriptive and retrospective, and does not provide ready explanations or solutions for the substantially worse outcomes experienced by this patient population. It does appear that outcomes are improved by providing early and aggressive care in designated trauma centers, yet undertriage remains a significant problem. Early admission to an ICU has been recommended, but its benefits remain unproved. Significant differences exist between older and younger patients in injury patterns, and in the frequency and type of complications These differences in turn demand prompt diagnostic approaches, aggressive treatment, and unique prevention strategies. Summary Ironically, the field of geriatric trauma is still in its infancy. Given the relation between advanced age, associated preexisting medical conditions, and poor physiologic reserve, a poor outcome may be inevitable by the time the geriatric patient presents for medical attention. Greater emphasis should therefore be placed on injury prevention efforts in this patient population. There is a dire need for well-designed prospective studies in geriatric trauma.

Special considerations in geriatric injury

Brain edema is still one of the most deleterious sequels of traumatic brain injury (TBI), and its pathophysiology is not sufficiently understood. The goal of the current study was to investigate the role of arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), an important regulator of tissue water homeostasis, for the formation of post-traumatic brain edema, intracranial pressure (ICP), brain damage, and functional deficits following brain trauma. C57/B16 mice (n=112) were subjected to controlled cortical impact (CCI; 8m/s, 1 mm). At 3 min after trauma, animals received 500 ng of the AVP V(1a)-receptor antogonist (deamino-Pen(1), O-Me-Tyr(2), Arg(8)]-Vasopressin) or 500 ng of the AVP V2-receptor antagonist (adamantaneacetyl(1), O-Et-D-Tyr(2),Val(4), Abu(6),Arg(8,9)]-Vasopressin) by intracerebroventricular injection. After trauma, cerebral water content (24 h), ICP (24 h), contusion volume (24 h and 7 days), and functional outcome (1-7 days) were assessed (n=8 per experimental group). Post-traumatic inhibition of AVP V(1A) receptors reduced ICP by 29% (p < 0.05), brain water content by 45% (p < 0.05), and secondary contusion expansion by 37% (p < 0.05), and it significantly improved motor function 6 and 7 days after trauma (p < 0.05). Inhibition of AVP V2 receptors had no significant effect. The current results demonstrate that vasopressin V(1A) receptors are involved in the pathogenesis of brain edema formation and the subsequent development of secondary brain damage after traumatic brain injury. Accordingly, our study suggests that vasopressin V(1A) receptors may represent a novel therapeutic target for the treatment of post-traumatic brain edema and secondary brain damage.

Role of Vasopressin V1a and V2 Receptors for the Development of Secondary Brain Damage after Traumatic Brain Injury in Mice

Background The purpose of the study was to compare initial resuscitation with arginine vasopressin (AVP), phenylephrine (PE), or isotonic crystalloid fluid alone after traumatic brain injury and vasodilatory shock. Study design Anesthetized, ventilated swine (n = 39, 30 ± 2 kg) underwent fluid percussion traumatic brain injury followed by hemorrhage (30 ± 2mL/kg) to a mean arterial pressure 60mmHg for 30 to 60minutes, then cerebral perfusion pressure > 60mmHg for 60 to 300minutes, either unlimited crystalloid fluid only (n = 9), arginine vasopressin + fluid (n = 9), phenylephrine + fluid (n = 9), arginine vasopressin only (n = 5), or phenylephrine only (n = 5). Heterologous transfusions were administered if hematocrit was 20 mmHg. Cerebrovascular reactivity was evaluated with serial CO 2 challenges. Results In all groups, physiologic variables were similar at baseline and at the end of shock. On resuscitation, all achieved mean arterial pressure and cerebral perfusion pressure goals. Brain tissue PO 2 s were similar. With fluid only, more blood and mannitol were required, intracranial pressure and peak inspiratory pressure were higher, and cerebrovascular reactivity was decreased (all p 2 saturation were similar to fluid only, but total fluid requirements and urine output were both reduced (p 2 saturation, cardiac output, and urine output were decreased (all p Conclusions To correct vasodilatory shock after traumatic brain injury, a resuscitation strategy that combined either phenylephrine or arginine vasopressin plus crystalloid was superior to either fluid alone or pressor alone.

Resuscitation with Pressors after Traumatic Brain Injury

Experimental evidence obtained in various animal models of brain injury indicates that vasopressin promotes the formation of cerebral edema. However, the molecular and cellular mechanisms underlying this vasopressin action are not fully understood. In the present study, we analyzed the temporal changes in expression of vasopressin V1a receptors after traumatic brain injury (TBI) in rats. In the intact brain, the V1a receptor was expressed in neurons located in all layers of the frontoparietal cortex. The V1a receptor-immunoreactive product was predominantly localized to neuronal nuclei and had both a diffused and punctate staining pattern. The V1a receptors were also expressed in astrocytes, especially in layer 1 of the frontoparietal cortex. In these cells, two distinctive patterns of immunopositive staining for V1a receptors were observed: a diffused cytosolic staining of cell bodies and processes and a clearly punctate staining pattern that was predominantly localized to the astrocytic cell bodies. The real-time reverse-transcriptase polymerase chain reaction analysis of changes in mRNA for the V1a receptor demonstrated that after TBI, there is an early (4 h post-TBI) increase in the number of transcripts in the ipsilateral frontoparietal cortex, when compared to the contralateral hemisphere or the sham-injured rats. This increase in the message was followed by the up-regulation of expression of the V1a receptors at the protein level. This was most evident in cortical astrocytes in the areas surrounding the lesion. The number of the V1a receptor-immunopositive astrocytes in the traumatized parenchyma gradually increased, starting at 8 h and peaking at 4-6 days after TBI. Furthermore, a redistribution of V1a receptors from the astrocytic cell bodies to the astrocytic processes was observed. In addition to astrocytes, an increased expression of V1a receptors was found in the endothelium of both blood microvessels and the large-diameter blood vessels in the frontoparietal cortex ipsilateral to injury. This increase in the V1a receptor expression was apparent between 2 and 4 days after TBI. As early as 1-2 h following the impact, there was also a striking increase in the number of the V1a receptor-immunopositive beaded axonal processes, with greatly enlarged varicosities, that were localized to various areas of the injured parenchyma. It is suggested that the increased expression of V1a receptors plays an important role in the vasopressin-mediated formation of edema in the injured brain.

Increased expression of vasopressin v1a receptors after traumatic brain injury.

Objective:Two series of experiments were designed to evaluate whether early arginine vasopressin improves acute outcome following resuscitation from traumatic brain injury and severe hemorrhagic hypotensionDesign:Prospective randomized, blinded animal study.Setting:University laboratory.Subjects:Thi

Effects of arginine vasopressin during resuscitation from hemorrhagic hypotension after traumatic brain injury.

OBJECTIVE To investigate the changes and clinical significance of arginine vasopressin (AVP) in elderly patients with acute traumatic cerebral injury. METHODS With radioimmunoassay, the plasma levels of AVP were measured in 32 elderly patients with acute traumatic cerebral injury, 30 traumatic patients without cerebral injury and 30 healthy elderly volunteers, respectively. RESULTS The plasma level of AVP in patients with acute traumatic cerebral injury in the early stage (48.30 ng/L +/- 8.28 ng/L) was much higher than that of the traumatic patients without cerebral injury (25.56 ng/L +/- 4.64 ng/L, P<0.01), which was much higher than that of the healthy volunteers (5.06 ng/L +/- 4.12 ng/L, P<0.01). The level of AVP in the patients with acute traumatic cerebral injury was negatively related with GCS scores. CONCLUSIONS AVP may play an important role in the pathophysiological process in patients with acute traumatic cerebral injury in the early stage. The severer the cerebral injury is, the higher the level of AVP is, which indicates that the level of AVP may be one of the severity indices of traumatic cerebral injury in elderly patients.

Yun-mei Yang

Papers

Changes of arginine vasopressin in elderly patients with acute traumatic cerebral injury.