Michael W. Cripps

Adult posttraumatic osteomyelitis of the tibia

Posttraumatic tibial osteomyelitis results from trauma or nosocomial infection from the treatment of trauma that allows organisms to enter bone, proliferate in traumatized tissue, and cause subsequent bone infection. The resulting infection is usually polymicrobial. The patient may be classified using the May and the Cierny-Mader classification systems. The diagnosis is based on the isolation of the pathogen(s) from the bone, or blood cultures. Appropriate therapy of posttraumatic tibial osteomyelitis includes adequate drainage, thorough debridement, obliteration of dead space, stabilization when necessary, wound protection, and specific antimicrobial therapy.

Criteria for empiric treatment of hyperfibrinolysis after trauma

BACKGROUND Recent studies identify a survival benefit from the administration of antifibrinolytic agents in patients with severe injury and trauma. However, identification of hyperfibrinolysis requires thromboelastography, which is not widely available. We hypothesized that analysis of patients with thromboelastography-diagnosed hyperfibrinolysis would identify clinical criteria for empiric antifibrinolytic treatment in the absence of thromboelastography. METHODS From November 2010 to March 2012, serial blood samples were collected from 115 patients with critical injury on arrival to the emergency department of an urban Level I trauma center. Rotational thromboelastography was performed to assess viscoelastic properties of clot formation in the presence and absence of aprotinin to identify treatable hyperfibrinolysis. For 20 patients identified with treatable hyperfibrinolysis, clinical predictors were investigated using receiver operating characteristic analysis. RESULTS Of the 115 patients evaluated, 20% had hyperfibrinolysis, defined as an admission maximal clot lysis of 10% or higher, reversible by aprotinin treatment. Patients with hyperfibrinolysis had significantly lower temperature, pH, and platelet counts and higher international normalized ratio, activated partial thromboplastin time, and D-dimer. Hyperfibrinolysis was associated with multiorgan failure (63.2% vs. 24.6%, p = 0.004) and mortality (52.2% vs. 12.9%, p < 0.001). We then evaluated all non–rotational thromboelastography clinical and laboratory parameters predictive of hyperfibrinolysis using receiver operating characteristic analysis to evaluate potential empiric treatment guidelines. The presence of hypothermia (temperature ⩽36.0°C), acidosis (pH ⩽7.2), relative coagulopathy (international normalized ratio ≥1.3 or activated partial thromboplastin time ≥30), or relative thrombocytopenia (platelet count ⩽200) identified hyperfibrinolysis with 100% sensitivity and 55.4% specificity (area under the curve, 0.777). CONCLUSION Consideration of empiric antifibrinolytic therapy is warranted for patients with critical injury and trauma who present with acidosis, hypothermia, coagulopathy, or relative thrombocytopenia. These clinical predictors identified hyperfibrinolysis with 100% sensitivity while simultaneously eliminating 46.6% of inappropriate therapy compared with the empiric treatment of all injured patients. These criteria will facilitate empiric treatment of hyperfibrinolysis for clinicians without access to thromboelastography. LEVEL OF EVIDENCE Prognostic study, level III.

Cause and timing of death in massively transfused trauma patients.

BACKGROUND The purpose of this study was to characterize the cause of death in severely injured trauma patients to define potential responses to resuscitation. METHODS Prospective analysis of 190 critically injured patients who underwent massive transfusion protocol (MTP) activation or received massive transfusion (>10 U of packed red blood cells [RBC] per 24 hours). Cause of death was adjudicated into one of four categories as follows: (1) exsanguination, (2) early physiologic collapse, (3) late physiologic collapse, and (4) nonsurvivable injury. RESULTS A total 190 patients underwent massive transfusion or MTP with 76 deaths (40% mortality), of whom 72 deaths were adjudicated to one of four categories: 33.3% died of exsanguination, 16.6% died of early physiologic collapse, 11.1% died of late physiologic collapse, while 38.8% died of nonsurvivable injuries. Patients who died of exsanguination were younger and had the highest RBC/fresh frozen plasma ratio (2.97 [2.24]), although the early physiologic collapse group survived long enough to use the most blood products (p < 0.001). The late physiologic collapse group had significantly fewer penetrating injuries, was older, and had significantly more crystalloid use but received a lower RBC/fresh frozen plasma ratio (1.50 [0.42]). Those who were determined to have a nonsurvivable injury had a lower presenting Glasgow Coma Scale (GCS) score, fewer penetrating injuries, and higher initial blood pressure reflecting a preponderance of nonsurvivable traumatic brain injury. The average survival time for patients with potentially survivable injuries was 2.4 hours versus 18.4 hours for nonsurvivable injuries (p < 0.001). CONCLUSION Severely injured patients requiring MTP have a high mortality rate. However, no studies to date have addressed the cause of death after MTP. Characterization of cause of death will allow targeting of surgical and resuscitative conduct to allow extension of the physiologic reserve time, therefore rendering previously nonsurvivable injury potentially survivable. LEVEL OF EVIDENCE Prognostic study, level III.

Thromboelastography and Rotational Thromboelastometry use in trauma

The appropriate resuscitation of patients in hemorrhagic shock is critical to improving survival. Current strategies for massive transfusions utilize fixed ratio protocols to rapidly deliver plasma and platelets to the patient. However, there is some concern that these larger volumes of transfusions can lead to untoward effects. Efforts are ongoing to provide patient-specific transfusion therapy in order to avoid excess transfusions. Thromboelastography (TEG) or Rotational Thromboelastometry (ROTEM) are two viscoelastic analyzers capable of providing Viscoelastic testing.

Lipoxin A4 Attenuates Microvascular Fluid Leak During Inflammation

BACKGROUND The release of proinflammatory cytokines during inflammation disturbs the endothelial barrier and can initiate significant intravascular volume loss. Proinflammatory cytokines also induce the expression of anti-inflammatory mediators, such as lipoxin, which promote the resolution of inflammation. Our hypothesis is that lipoxin A(4) (LXA(4)) reverses the increased microvascular fluid leak observed during inflammatory conditions. MATERIALS AND METHODS Microvascular fluid leak (L(p)) was measured in rat mesenteric venules using a micro-cannulation technique. L(p) was measured under the following conditions: (1) LXA(4) (100 nM) alone (n = 5), (2) LXA(4) (100 nM) administered after endothelial hyperpermeability induced by a continuous perfusion of 10 nM platelet activating factor (PAF) (n = 5), (3) LXA(4) (100 nM) perfused after inflammation induced by a systemic bolus of 10 mg/kg lipopolysaccharide (LPS) (n = 5), and (4) LXA(4) (100 nM) perfused after LPS-induced inflammation during inhibition of c-Jun N-terminal kinase (n = 4). RESULTS LXA(4) alone slightly increased L(p) from baseline (L(p)-baseline = 1.05 +/- 0.03, L(p)-LXA(4) = 1.55 +/- 0.04; P < 0.0001). PAF increased L(p) 4-fold (L(p)-baseline = 1.20 +/- 0.10, L(p)-PAF = 4.49 +/- 0.95; P < 0.0001). LXA(4) administration after PAF decreased L(p) 66% versus PAF alone (from 4.49 +/- 0.95 to 1.54 +/- 0.13; P = 0.0004). LPS-induced inflammation increased L(p) over 2-fold (L(p)-baseline = 1.05 +/- 0.03, L(p)-LPS = 2.27 +/- 0.13; P < 0.0001). LXA(4) administration after LPS decreased L(p) 42% versus LPS alone (from 2.27 +/- 0.13 to 1.31 +/- 0.05; P < 0.0001). The effect of c-Jun N-terminal kinase inhibition during LPS-induced inflammation attenuated the decrease in leak cause by LXA(4) by 51% (P = 0.0002). CONCLUSION After either LPS or PAF, LXA(4) attenuated the intravascular volume loss caused by these inflammatory mediators. The activity of LXA(4) may be partly mediated by the c-Jun N-terminal kinase signaling pathway. These data support an anti-inflammatory role for LXA(4) and suggests a potential pharmacologic role for LXA(4) during inflammation.

The Massive Transfusion Score as a decision aid for resuscitation: Learning when to turn the massive transfusion protocol on and off.

BACKGROUND Previous work proposed a Massive Transfusion Score (MTS) calculated from values obtained in the emergency department to predict likelihood of massive transfusion (MT). We hypothesized the MTS could be used at Hour 6 to differentiate who continues to require balanced resuscitation in Hours 7 to 24 and to predict death at 28 days. METHODS We prospectively enrolled patients in whom the MT protocol was initiated from 2005 to 2011. Data including timing of blood products were determined at Hours 0, 6, 12, and 24. For each patient, transfusion needs were defined based on either an inappropriately low hemoglobin response to transfusion or a hemoglobin decrease of greater than 1 g/dL if no transfusion. Timing and cause of death were used to account for survivor bias. Multivariate logistic regression was used to determine independent predictors of outcome. RESULTS A total of 190 MT protocol activations were included, and by Hour 6, 61% required 10 U or greater packed red blood cells. Calculated at initial presentation, a revised MTS (systolic blood pressure < 90 mm Hg, base deficit ≥ 6, temperature < 35.5°C, international normalized ratio > 1.5, hemoglobin < 11 g/dL) was superior to the original MTS (including heart rate ≥ 120 beats per minute, Focused Assessment With Sonography in Trauma [FAST] status, mechanism) or the Assessment of Blood Consumption (ABC) score for predicting MT (area under the curve [AUC] MT at 6 hours, 0.68; 95% confidence interval [CI], 0.57–0.79; at 24 hours, 0.72; 0.61–0.83; p < 0.05). For those alive at Hour 6, the revised MTS was predictive of future packed red blood cell need (AUC, 0.87) in Hours 7 to 12, 24-hour mortality (AUC, 0.95), and 28-day mortality (AUC, 0.77). For each additional positive trigger of the MTS at Hour 6, the odds of death at 24 hours and 28 days were substantially increased (24-hour odds ratio, 4.6; 95% CI, 2.3–9.3; 28-day odds ratio, 2.2; 95% CI, 1.5–3.2; p < 0.0001). CONCLUSION Early end points of resuscitation adopted from the components of the revised MTS are predictive of ongoing transfusion. Failure to normalize these components by Hour 6 portends a particularly poor prognosis. LEVEL OF EVIDENCE Prognostic study, level 3.

The Parkland Burn Center experience with 297 cases of child abuse from 1974 to 2010

INTRODUCTION Pediatric burns due to abuse are unfortunately relatively common, accounting for 5.8-8.8% of all cases of abuse annually. Our goal was to evaluate our 36-year experience in the evaluation and management of the victims of abuse in the North Texas area. METHODS A prospectively maintained database containing records on all admissions from 1974 through 2010 was queried for all patients aged less than 18 years. Patients admitted for management of a non-burn injury were excluded from the analysis. RESULTS Of 5,553 pediatric burn admissions, 297 (5.3%) were due to abuse. Children with non-accidental injuries tended to be younger (2.1 vs. 5.0 years, p<0.0001) and male (66.0 vs. 56.5%, p=0.0008). Scald was the most common mechanism of injury overall (44.8%), and was also the predominant cause of inflicted burns (89.6 vs. 42.3%, p<0.0001). Multivariate logistic regression identified age, gender, presence of a scald, contact, or chemical burn, and injury to the hands, bilateral feet, buttocks, back, and perineum to be significant predictors of abuse. Victims of abuse were also found to have worse outcomes, including mortality (5.4 vs. 2.3%, p=0.0005). After adjusting for age, mechanism of injury, and burn size, abuse remained a significant predictor of mortality (OR 3.3, 95% CI 1.5-7.2) CONCLUSIONS: Clinicians should approach all burn injuries in young children with a high index of suspicion, but in particular those with scalds, or injuries to the buttocks, perineum, or bilateral feet should provoke suspicion. Burns due to abuse are associated with worse outcomes, including length of stay and mortality.

Transfusion of cryopreserved packed red blood cells is safe and effective after trauma a prospective randomized trial

OBJECTIVES To determine the safety and efficacy of cryopreserved packed red blood cell (CPRBC) transfusion in trauma patients. BACKGROUND Liquid packed red blood cells (LPRBCs) have an abbreviated shelf-life and worsening storage lesion with age. CPRBCs are frozen 2 to 6 days after donation, stored up to 10 years, and are available for 14 days after thawing and washing. CPRBCs can be utilized in diverse settings, but the effect on clinical outcomes is unknown. METHODS We performed a prospective, randomized, double-blind study at 5 level 1 trauma centers. Stable trauma patients requiring transfusion were randomized to young LPRBCs (≤14 storage days), old LPRBCs (>14 storage days), or CPRBCs. Tissue oxygenation (StO2), biochemical and inflammatory mediators were measured, and clinical outcomes were determined. RESULTS Two hundred fifty-six patients with well-matched injury severity and demographics (P > 0.2) were randomized (84 young, 86 old, and 86 CPRBCs). Pretransfusion and final hematocrits were similar (P > 0.68). Patients in all groups received the same number of units postrandomization (2 [1-4]; P > 0.05). There was no difference in the change in tissue oxygenation between groups. CPRBCs contained less α2-macrogobulin, haptoglobin, C-reactive protein, and serum amyloid P (P < 0.001). Organ failure, infection rate, and mortality did not differ between groups (P > 0.2). CONCLUSIONS Transfusion of CPRBCs is as safe and effective as transfusion of young and old LPRBCs and provides a mechanism to deliver PRBCs in a wide variety of settings.

Ventilator-Associated Pneumonia: New Definitions

The National Healthcare Safety Network’s new classification characterizes all adverse ventilator-associated events (VAE) into a tiered system designed to shift the focus away from ventilator-associated pneumonia as the only important cause or morbidity in ventilated patients. This new surveillance definition of VAE eliminates subjectivity by using clearly defined criteria and facilitates the automated collection of data. This allows for easier comparison and analysis of factors affecting rates of VAE. Numerous studies have been published that demonstrate its clinical application. This article presents the VAE criteria, contrasts the difference from the previous ventilator-associated pneumonia definition, and discusses its implementation over the past 5 years.

The effect of hypoxia, reoxygenation, ischemia, and reperfusion on hydraulic permeability in rat mesenteric venules.

Little is known regarding the effects of I/R on hydraulic permeability (Lp). We sought to compare the individual influences of hypoxia, ischemia, reoxygenation, and reperfusion on Lp. We hypothesized that (1) hypoxia increases Lp; (2) reoxygenation further increases Lp; (3) ischemia results in greater increases in Lp compared with hypoxia; (4) reperfusion causes additional increases in Lp compared with hypoxia, ischemia, and reoxygenation; and (5) xanthine oxidase (XO) and white blood cell adherence play important roles in hypoxia, ischemia, and reperfusion. Hydraulic permeability was measured by an in vivo microcannulation technique during hypoxia, reoxygenation, ischemia, and reperfusion in rat mesenteric postcapillary venules. Additional rats were fed a Tungsten-enriched diet to inhibit XO activity, and the studies were repeated. White blood cell adherence was also documented. Hypoxia and ischemia both increased Lp 2-fold from baseline levels (P < 0.001). Reoxygenation did not alter Lp compared with 15 min of hypoxia alone (P > 0.07). Reperfusion after hypoxia increased Lp 6-fold (P < 0.001). Reperfusion after ischemia also increased Lp 6-fold (P < 0.001). Inhibition of XO had no effect on the increase in Lp after both hypoxia and ischemia. However, inhibition of XO attenuated the 6-fold increase in Lp observed during reperfusion after both hypoxia and ischemia by approximately 50% (P < 0.001). White blood cell adherence increased during reperfusion but not hypoxia or ischemia. The complexity of I/R injury makes it a difficult clinical scenario to model for research. We have demonstrated in an in vivo model that hypoxia and ischemia increase Lp similarly, and that reperfusion has a profound deleterious effect on Lp. These changes in Lp seem to be XO and white blood cell dependent.