Admission ionized calcium levels predict the need for multiple transfusions: a prospective study of 591 critically ill trauma patients.

BACKGROUND: Deaths from uncontrolled exsanguinating hemorrhage occur rapidly postinjury. Any successful resuscitation strategy must also occur early, underscoring the importance of rapid identification of patients at risk for multiple transfusions. Previous studies have shown low ionized calcium (iCa) levels to be associated with hypotension and function as a predictor of mortality. We hypothesized that admission iCa levels could potentially predict the need for multiple transfusions in critically ill trauma patients. METHODS: Admission iCa was collected prospectively on all trauma activations during a 9-month period. Youden's index was used to determine the appropriate cutpoint for iCa. Outcomes (mortality, multiple transfusions [≥5 units packed red blood cells in 24 hours] and massive transfusion [≥10 units packed red blood cells in 24 hours]) were compared using Wilcoxon rank-sum and χ tests where appropriate. Multivariable logistic regression was performed to determine whether iCa was an independent predictor of multiple transfusions. RESULTS: A total of 591 patients were identified: 461 (78%) men and 130 (22%) women. Cutpoint was identified as 1.00. iCa was <1.00 (lo-Cal) in 332 patients and≥1.00 (hi-Cal) in 259 patients. Mortality was significantly increased in the lo-Cal group (15.5% vs. 8.7%, p=0.036). In addition, both multiple transfusions (17.1% vs. 7.1%, p=0.005) and massive transfusion (8.2% vs. 2.2%, p=0.017) were significantly increased in the lo-Cal group. Multivariable logistic regression analysis identified iCa<1 as an independent predictor of the need for multiple transfusions after adjusting for age and injury severity (odds ratio=2.294, 95% confidence interval=1.053-4.996). CONCLUSIONS: Low iCa levels at admission were associated with increased mortality as well as an increased need for both multiple transfusions and massive transfusion. In fact, multivariable logistic regression analysis identified low iCa levels as an independent predictor of multiple transfusions. Admission iCa levels may facilitate the rapid identification of patients requiring massive transfusion, allowing for earlier preparation and administration of appropriate blood products.

Trauma-induced coagulopathy: The past, present, and future.

Trauma remains a leading cause of death worldwide, and most early preventable deaths in both the civilian and military settings are due to uncontrolled hemorrhage, despite paradigm advances in modern trauma care. Combined tissue injury and shock result in hemostatic failure, which has been identified as a multidimensional molecular, physiologic and clinical disorder termed trauma-induced coagulopathy (TIC). Understanding the biology of TIC is of utmost importance, as it is often responsible for uncontrolled bleeding, organ failure, thromboembolic complications, and death. Investigations have shown that TIC is characterized by multiple phenotypes of impaired hemostasis due to altered biology in clot formation and breakdown. These coagulopathies are attributable to tissue injury and shock, and encompass underlying endothelial, immune and inflammatory perturbations. Despite the recognition and identification of multiple mechanisms and mediators of TIC, and the development of targeted treatments, the mortality rates and associated morbidities due to hemorrhage after injury remain high. The purpose of this review is to examine the past and present understanding of the multiple distinct but highly integrated pathways implicated in TIC, in order to highlight the current knowledge gaps and future needs in this evolving field, with the aim of reducing morbidity and mortality after injury.

Exsanguinating bleeding following tooth extraction in a 12-year-old girl: a rare case of acquired haemophilia A.

Acquired haemophilia A (AHA) is a life-threatening haemorrhagic disorder that occurs with various underlying conditions such as autoimmune disease, drug reactions, lymphoproliferative diseases, solid tumours and pregnancy/postpartum status. However, in half of all reported cases, the underlying disease is unknown. Most AHA cases develop in adults; paediatric/adolescent cases are extremely rare. The main clinical symptom is bleeding into the skin, muscles, soft tissues and/or mucous membranes. Here, we report the case of an otherwise healthy 12-year-old girl who presented with prolonged bleeding postexodontia. After being diagnosed with AHA, she was successfully treated with recombinant activated factor VII infusion and oral prednisolone. To avoid such unanticipated bleeding when performing dental extraction, preoperative haemostatic screening tests are recommended.

Hemostatic resuscitation is neither hemostatic nor resuscitative in trauma hemorrhage.

BACKGROUND: Trauma hemorrhage continues to carry a high mortality rate despite changes in modern practice. Traditional approaches to the massively bleeding patient have been shown to result in persistent coagulopathy, bleeding, and poor outcomes. Hemostatic (or damage control) resuscitation developed from the discovery of acute traumatic coagulopathy and increased recognition of the negative consequences of dilutional coagulopathy. These strategies concentrate on early delivery of coagulation therapy combined with permissive hypotension. The efficacy of hemostatic resuscitation in correcting coagulopathy and restoring tissue perfusion during acute hemorrhage has not been studied. METHODS: This is a prospective cohort study of ROTEM and lactate measurements taken from trauma patients recruited to the multicenter Activation of Coagulation and Inflammation in Trauma (ACIT) study. A blood sample is taken on arrival and during the acute bleeding phase after administration of every 4 U of packed red blood cells (PRBCs), up to 12 U. The quantity of blood products administered within each interval is recorded. RESULTS: Of the 106 study patients receiving at least 4 U of PRBC, 27 received 8 U to 11 U of PRBC and 31 received more than 12 U of PRBC. Average admission lactate was 6.2 mEq/L. Patients with high lactate (≥5 mEq/L) on admission did not clear lactate until hemorrhage control was achieved, and no further PRBC units were required. On admission, 43% of the patients were coagulopathic (clot amplitude at 5 minutes ≤ 35 mm). This increased to 49% by PRBC 4; 62% by PRBC 8 and 68% at PRBC 12. The average fresh frozen plasma/PRBC ratio between intervals was 0.5 for 0 U to 4 U of PRBC, 0.9 for 5 U to 8 U of PRBC, 0.7 for 9 U to 12 U of PRBC. There was no improvement in any ROTEM parameter during ongoing bleeding. CONCLUSION: While hemostatic resuscitation offers several advantages over historical strategies, it still does not achieve correction of hypoperfusion or coagulopathy during the acute phase of trauma hemorrhage. Significant opportunities still exist to improve management and improve outcomes for bleeding trauma patients. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Diet-induced obesity prevents the development of acute traumatic coagulopathy.

BACKGROUND: Obesity and hemorrhagic shock following trauma are predictors of mortality but have conflicting effects on coagulation. Following hemorrhage, tissue injury and hypoperfusion lead to acute traumatic coagulopathy (ATC), producing a hypocoagulable state. Inversely, obesity promotes clotting and impairs fibrinolysis to yield a hypercoagulable state. High rates of venous thromboembolism, organ failure, and early mortality may be caused by hypercoagulability in obese patients. We hypothesize that obesity prevents the development of ATC following injury-induced hemorrhagic shock. METHODS: Male Sprague-Dawley rats (250-275 g) were fed a high-fat diet (32%kcal from fat) for 4 weeks to 6 weeks and diverged into obesity-resistant (OR, n = 9) and obesity-prone (OP, n = 9) groups. Age-matched control (CON) rats were fed normal diet (10% kcal from fat, n = 9). Anesthetized rats were subjected to an uncontrolled hemorrhage by a Grade V splenic injury to a mean arterial pressure (MAP) of 40 mm Hg. Hypotension (MAP, 30-40 mm Hg) was maintained for 30 minutes to induce shock. MAP, heart rate, lactate, base excess, cytokines, blood loss, and thrombelastography (TEG) parameters were measured before and after hemorrhagic shock. RESULTS: At baseline, OP rats exhibited a shorter time to 20-mm clot (K), and higher rate of clot formation (α angle), clot strength (maximal amplitude), and coagulation index, compared with the CON rats (p < 0.05), indicating enhanced coagulation. Physiologic parameters following shock were similar between groups. In the CON and OR rats, shock prolonged the time to clot initiation (R) and K and decreased α angle and coagulation index (all p < 0.05 vs. baseline). In contrast, shock had no effect on these TEG parameters in the OP rats. Maximal amplitude was the only TEG parameter affected by shock in the OP rats, which was decreased in all groups. CONCLUSION: Obesity prevents the development of ATC following hemorrhage shock. Complications associated with obesity following hemorrhagic shock may be attributed to the preserved hypercoagulable state.

Targeted resuscitation improves coagulation and outcome.

BACKGROUND: Acute trauma coagulopathy in seriously injured casualties may be initiated by tissue hypoperfusion. A targeted (or novel hybrid [NH]) resuscitation strategy was developed to overcome poor tissue oxygen delivery associated with prolonged hypotension. METHODS: Under the Animals (Scientific Procedures) Act 1986, terminally anesthetized large white pigs were divided into four groups (n = 6). Groups 1 and 2 received blast injury and 3 and 4 no blast (sham). All were given a controlled hemorrhage (35% blood volume) and an uncompressed grade IV liver injury. Five minutes later, all were resuscitated with 0.9% saline to a systolic arterial pressure (SAP) of 80 mm Hg. After 60 minutes, the NH groups (1 and 3) were resuscitated to a SAP (110 mm Hg), whereas hypotensive groups (2 and 4) continued with SAP 80 mm Hg for up to 8 hours from onset of resuscitation. RESULTS: Mean survival time was shorter in group 2 (258 minutes) compared with groups 1, 3, and 4 (452 minutes, 448 minutes, and 369 minutes). By the end of the study, hypotension was associated with a significantly greater prothrombin time (1.73 ± 0.10 and 1.87 ± 0.15 times presurgery, groups 2 and 4) compared with NH (1.44 ± 0.09 and 1.36 ± 0.06, groups 1 and 3, p = 0.001). Blast versus sham had no significant effect on prothrombin time (p = 0.56). Peak levels of interleukin 6 were significantly lower in NH groups. Arterial base excess was significantly lower with hypotension (-18.4 mmol/L ± 2.7 mmol/L and -12.1 mmol/L ± 3.2 mmol/L) versus NH (-3.7 mmol/L ± 2.8 mmol/L and -1.8 mmol/L ± 1.8 mmol/L, p = 0.0001). Hematocrit was not significantly different between groups (p = 0.16). CONCLUSION: Targeted resuscitation (NH) attenuates the development of acute trauma coagulopathy and systemic inflammation with improved tissue perfusion and reduced metabolic acidosis in a model of complex injury. This emphasizes the challenge of choosing a resuscitation strategy for trauma patients where the needs of tissue perfusion must be balanced against the risk of rebleeding during resuscitation.

Risk factors of mortality in non-trauma exsanguinating patients that require damage control laparotomy.

BACKGROUND: Since introduction of damage control (DC) approach to non-trauma setting is relatively late, the risk factors associated with this procedure remain undefined. This study was aimed at identifying factors responsible for the mortality. METHODS: Over a 5-year period (from February 2002 to February 2007), consecutive non-trauma patients who required DC laparotomy (DCL) with gauze packing for control of indomitable abdominal haemorrhage in our institute were included. Clinical, laboratorial and operative factors influencing in-hospital or 30-day mortality were analysed. RESULTS: A total of 26 patients underwent DCL with packing in an attempt to control severe abdominal haemorrhage. There were seven (26.9%) deaths in hospital or within 30 days of DCL. Increase in age, higher initial physiological score and operative severity score assessed by the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity scoring system, lower initial body temperature, lower initial platelet (PLT) counts, greater intra-operative blood loss, presence of perioperative multiple organ dysfunction syndrome were all associated with increased risk of mortality on univariate analysis (P < 0.05). On multivariate analysis, only decrease in PLT counts (P = 0.042, OR = 0.969, 95% CI = 0.940-0.999) and increase in age (P = 0.035, OR = 1.152, 95% CI = 1.010-1.313) were significant independent factors affecting mortality. CONCLUSIONS: Decrease in PLT counts and increase in age are the independent risk factors related to death in non-trauma series that require DCL with packing. DCL should be performed early as for patients with these risk factors.