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Article 1
Early resuscitation with fresh frozen plasma for traumatic brain injury combined with hemorrhagic shock improves neurologic recovery. Halaweish I, Bambakidis T, He W, Linzel D, Chang Z, Srinivasan A, Dekker SE, Liu B, Li Y, Alam HB. J Am Coll Surg. 2015 May; 220:809-19.
TBI patients, due to the release of tissue factors and platelet dysfunction, are especially prone to coagulation disorders and bleeding. In turn, the combination of TBI and hemorrhagic shock worsens TBI associated morbidity and mortality. Resulting tissue hypoxia leads to increased cerebral edema, ICP elevation and cell death resulting in secondary brain injury. The authors sought to determine if FFP resuscitation after TBI with hemorrhagic shock would result in improved long-term neurologic recovery as measured by Neurologic Severity Score (NSS). Ten swine were subjected to a severe but survivable TBI and animals were hemorrhaged 40% of their blood volume. Animals were kept in shock for 2hrs and then randomized to either saline or FFP resuscitation groups. FFP was transfused in volumes equal to shed blood while resuscitated saline volumes equaled 3x shed blood. Neurologic Severity Scores were assessed daily for 30 days by a blinded observer. Swine also underwent cognitive function testing along with brain MRI imaging 3, 10, and 24 days following injury.
While saline increased MAPs to near baseline levels, FFP increased MAPs to greater than baseline levels. Neurologic impairment was significantly less in FFP resuscitated swine during the early post-injury period, and these animals also demonstrated more rapid recovery in their NSS. Saline treated animals required longer before cognitive function testing was possible although brain lesion size on MRI was not different between study groups throughout the study duration. This study has analyzed a challenging clinical scenario with 2hrs of severe hemorrhagic shock and concomitant TBI. NSS differences between saline and FFP resuscitated swine were most pronounced early after injury, but diminished over the study period before becoming nonexistent after 30 days. Although the study sample size is small, one conclusion that may be drawn is that saline and FFP resuscitation after TBI with hemorrhagic shock are equivalent methods of resuscitation. An important consideration though, is that the early and rapid recovery of neurologic impairment is most likely to benefit the very patient that this study is based on: the multi-system trauma victim with severe TBI and hemorrhagic shock who would benefit from early recovery, therapy, and rehabilitation.
Article 2
Impact of Hemorrhagic Shock on Pituitary Function. Joseph B, Haider AA, Pandit V, Kulvatunyou N, Orouji T, Khreiss M, Tang A, O'Keeffe T, Friese R, Rhee P. J Am Coll Surg. 2015 Aug; 221:502-8.
Hemorrhagic shock remains the most common cause of death in trauma victims and stress hormones play a vital role in homeostasis after hemorrhage. The authors analyzed pituitary and cortisol levels after hemorrhagic shock. A 9 month prospective, observational study was performed on patients presenting with hemorrhagic shock (SBP<90mmHg or ED transfusion ≥2 units RBCs) and cortisol, vasopressin, adrenocorticotrophic hormone (ACTH), thyroid stimulating hormone (TSH), follicular stimulating hormone (FSH), and luteinizing hormone (LH) serum levels were assessed at 0, 24, 48, 72, and 96 hours after admission. Values were associated with clinical variables and compared on the basis of survival.
Studied patients (n=42) were critically injured (mean admission SBP 85 ± 65mmHg, median ISS 26 [18-38], MTP activation 52%, surgical intervention 81%). Overall, there was a significant decrease in ACTH and ADH levels over time while TSH, FSH and LH levels remained unchanged and serum cortisol levels increased. When survivors were compared to nonsurvivors, no differences in most clinical parameters were observed including age, injury mechanism, admission SBP, heart rate, GCS, ISS, administration of etomidate, and blood product transfusion. Among the 32 survivors, serum cortisol increased while ACTH and vasopressin levels decreased (0 vs. 96hr comparison) over the study period. Nonsurvivors (n=10) experienced a significant decrease in cortisol levels (14±7 vs. 6±1; p=0.03) while ACTH, TSH, and FSH levels remained unchanged (0 vs. 96hr comparison). Hormone levels were then compared between survivors and nonsurvivors (n=4) at the 96 hour study point. Survivors had lower ACTH levels (29±11 vs. 47±4 pg/mL; p=0.002) and greater cortisol levels (36±11 vs. 6±1 pg/mL; p<0.001) but no difference in vasopressin, TSH, FSH or LH levels were appreciated between survivors and nonsurvivors was appreciated 96 hours after hemorrhagic shock. Moreover, 75% and 19% of the study population had relative and severe adrenal insufficiency, likely as a result of decreased adrenal perfusion during hemorrhagic shock. Before treated patients in hemorrhagic shock with steroids, we must first answer an important question though: is hypocortisolism simply a marker for poor outcome after hemorrhagic shock or is there a causal relationship between hypocortisolism and adverse outcomes?
Article 3
Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Goldstein JN, Refaai MA, Milling TJ Jr, Lewis B, Goldberg-Alberts R, Hug BA, Sarode R.
Lancet. 2015 May; 385:2077-87.
As our population ages, the use of vitamin K antagonists (VKA) is becoming increasingly common in trauma patients. Vitamin K and fresh frozen plasma (FFP) remain as the most common agents to reverse coagulopathy in patients at risk for hemorrhage. However, FFP requires ABO typing, thawing, and prolonged infusion times which may create risk for additional bleeding while awaiting reversal or volume overload. In this prospective, international, 33 center, unblinded clinical trial, adults on VKA with an INR ≥2.0 requiring surgery or invasive procedures within 24hrs were randomized to either vitamin K plus FFP or vitamin K plus 4 factor prothrombin complex concentrate (4F-PCC) for reversal. FFP and 4F-PCC were dosed by weight although vitamin K administration was not standardized by study protocol. The primary study endpoints were effective hemostasis during the surgical procedure (a largely subjective assessment) and rapid INR reversal (INR ≤ 1.3 measured 30 minutes after FFP or 4F-PCC infusion).
Plasma (n=81) and 4F-PCC (n=87) groups were similar at baseline with respect to demographics, INR, indication for VKA therapy, type of surgical procedure, and vitamin K dosing. Patients randomized to the 4F-PCC group exhibited better hemostasis (90% vs. 75%, p=0.0142) and more often rapid INR reversal (55% vs. 10%, p<0.0001) than FFP treated counterparts. Accordingly, elapsed median time from infusion until surgical procedure start was less in the 4F-PCC group (3.6hrs vs. 8.5hrs, p=0.0098). There was no statistical difference overall adverse events or treatment related adverse events, although volume overload was more common (13%) in FFP reversed patients. Although this study was funded, designed, managed and overseen by CSL Behring (4F-PCC manufacturer), this well-designed trial adds greatly to the small but growing body of literature reporting the superiority of 4F-PCC over plasma. While this trial did not include hemorrhaging trauma patients or patients with traumatic brain injury, parallels and extrapolation to these populations are clear. Trauma specific questions remain though. Only 2 patients underwent neurosurgical procedures in this study—perhaps the very group that is most pertinent when TBI and rapid coagulopathy reversal is considered. Lastly, the nature of the delay until INR reversal remains unclear. If the delay is due to the thawing of frozen plasma, then use of fresh stored plasma which does not require thawing offers a more rapid alternative that many trauma centers have already adapted.
Article 4
Mindfulness-Based Stress Reduction for Posttraumatic Stress Disorder Among Veterans: A Randomized Clinical Trial. Polusny MA, Erbes CR, Thuras P, Moran A, Lamberty GJ, Collins RC, Rodman JL, Lim KO.
JAMA. 2015 Aug; 314:456-65.
After decades of neglect, posttraumatic stress disorder is finally receiving the attention it deserves. Posttraumatic stress disorder (PTSD) has been diagnosed in 23% of veterans returning back from Iraq and Afghanistan and leads to comorbidity, disability, and poor quality of life. Mindfulness-based stress reduction is an intervention that teaches patients to attend to the present moment without avoidance of painful experiences in an accepting manner to relieve depression and anxiety. Patients were randomized to mindfulness-based stress reduction therapy (n=58; 8 weekly 2.5hr group sessions) or control, a present-centered group therapy (n=58; 9 weekly 1.5hr group sessions) study groups. The change in PTSD severity assessed by the PTSD checklist (range 17-85, higher scores indicate greater severity) was followed over time at baseline, 3, 6, 9, and 17 weeks after therapy initiation.
No difference between study groups was appreciated with respect to demographics, service era, traumatic event type, baseline PTSD severity or assessment scores. Study participants randomized to the mindfulness-based stress reduction therapy arm showed greater improvement in PTSD symptom severity both during treatment (64 to 56 vs. 59 to 56, p=0.002) and during a 2 month follow-up session (64 to 54 vs. 59 to 56, p<0.00). Furthermore, veterans in the mindfulness-based stress reduction therapy arm were more likely to have clinical improvement in PTSD symptoms (49% vs 28%, p=0.03) along with improvements in both depressive symptoms and quality of life after treatment while the present-centered therapy group did not. While this is a single center study of primarily white (84%) males (84%) from the Vietnam conflict (75%), this study has important implications for all of our patients who have survived a major traumatic event.
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