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Pharmacokinetics and pharmacodynamics of enoxaparin in multiple trauma patients.

BACKGROUND: Enoxaparin is the only low molecular-weight heparin (LMWH) with documented efficacy for the prevention of venous thromboemobolism (VTE) following trauma, and it is currently considered the treatment of choice. Recent reports have suggested that the pharmacokinetics (PK) and pharmacodynamics of LMWH products may be altered in critically ill patients. METHODS: Two cohorts of critically ill multiple trauma patients were enrolled in this study: A (nonedematous) and B (edematous, defined as the presence of peripheral edema and an increase in body weight of > or =10 kg). All patients received at least four doses of enoxaparin 30 mg subcutaneously every 12 hours before the study dose. Blood samples were collected before and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours following a morning dose. Plasma anti-Xa and antithrombin (AT) activities were determined using chromogenic assays. A compartmental PK analysis model was defined for the data. PK parameters for the two cohorts were compared using a Mann-Whitney Rank Sum test. RESULTS: The area under the curve (AUC)0-12 hour, maximal plasma anti-activated Factor Xa (anti-Xa) activity (Amax), and AT activity were significantly lower in the edematous trauma patients (p < 0.05). The AUC0-12 hour for plasma anti-Xa activity was highly variable in both study cohorts. Seven of the 10 edematous patients had barely quantifiable anti-Xa results. Activity levels were too low to reliably estimate the PK parameters for most patients in cohort B. CONCLUSION: The standard dose of enoxaparin recommended for the prevention of VTE following multiple trauma provides unreliable and highly variable anti-Xa activity in critically ill trauma patients, and is strongly affected by the presence of significant peripheral edema.

Adult↗

Is the timing of fracture fixation important for the patient with multiple trauma?

OBJECTIVE: The effect of timing of femur fracture fixation for patients with multiple trauma was studied to determine the effect of operative timing on eventual outcome. METHODS: The relationship between timing of intramedullary rod (IMR) placement, degree of injury, and pulmonary complications was studied in 424 consecutive patients. The authors focused on 105 patients undergoing IMR placement with an Injury Severity score (ISS) of greater than or equal to 18. The effects of timing of IMR placement on various pulmonary complications, organ failure, intensive care unit (ICU) admission, and ventilatory assistance were studied for various time intervals. RESULTS: Of the 424 patients, pulmonary complications increased slightly in the more seriously injured group (ISS > 18) but were not influenced by the timing of IMR placement. Of the 105 patients undergoing IMR placement with an ISS > or = 18, only 2 patients died. Both patients had an IMR placed in less than 24 hours and died later of head injury and delayed hemorrhage. The incidence of organ failure, number of ventilator days, and length of ICU stay did not differ between the groups based on timing of fracture fixation. The incidence of severe head injuries was higher in the group undergoing delayed IMR placement (> 48 hours). CONCLUSIONS: Modest delays in IMR placement did not adversely affect patient outcome. Pulmonary complications were related to the severity of injury rather than to timing of fracture fixation. In a well-integrated trauma system, clinical judgment regarding the timing of IMR placement was the most important determinant of outcome. Delays that were made to stabilize the patient, treat associated injuries, and plan orthopedic reconstruction did not adversely affect patient outcome.

Adult↗

Long-term (6-year) effect of selective digestive decontamination on antimicrobial resistance in intensive care, multiple-trauma patients.

OBJECTIVE: To determine whether selective digestive decontamination (SDD) had some negative impact on the bacterial resistance observed in strains isolated from samples from patients receiving nonabsorbable antibiotics and cefazolin. DESIGN: Case-control study. SETTING: Intensive care unit of a university tertiary-care hospital. PATIENTS: Over a 6-yr period, 360 multiple trauma patients (case patients) submitted to SDD were compared with 360 patients not receiving SDD (controls). INTERVENTIONS: SDD consisted of polymyxin E, gentamicin, and amphotericin B and was applied on the buccal mucosa and provided in the nares and the stomach. For the first 3 days, systemic cefazolin (1 g three times a day) was provided. Resistance analysis was performed in case patients and controls on samples collected at predetermined intervals. MEASUREMENTS AND MAIN RESULTS: SDD was used in a small subset of patients admitted to the intensive care unit (360 of 5987 over the 6-yr study period). A relative overgrowth of gram-positive cocci was observed. Methicillin resistance of Staphylococcus epidermidis was increased (SDD 76%, controls 63%, p <.05) but not that of Staphylococcus aureus (SDD 20%, controls 18%). Resistance of Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter to beta-lactamines and aminoglycosides was the same in SDD patients and controls. CONCLUSIONS: When used in a small subset of patients who have been shown to derive benefit from it (patients who have experienced multiple trauma), SDD has a moderate impact on microbial ecology. However, surveillance cultures are indispensable because the absence of resistance to SDD antibiotics determines the long-term safety of the SDD prophylaxis.

APACHE↗

Delayed epidural hemorrhage in hypotensive multiple trauma patients.

Despite the availability of high resolution computed tomography, severely head-injured patients often present diagnostic dilemmas. An initially negative computed tomographic scan in the presence of severe multiple trauma does not predict an uncomplicated course. Early repeat scanning should be considered. We present three cases of delayed epidural hemorrhage in multiple trauma patients who initially were hypotensive secondary to hypovolemia. Possible etiologies for the hemorrhage as well as a list of indications for repeat scanning in the posttraumatic period are discussed.

Adolescent↗

Quality of life after multiple trauma requiring intensive care.

A prospective observational study using structured interviews was used to assess changes in quality of life experienced by surviving trauma victims after management on a general intensive therapy unit in a district general hospital. Each patient's age, distribution of injuries, severity of illness on admission and duration of management were recorded. Deaths in the study group were excluded by examining the Hospital's 'Patient Administrative System'. Three attempts were then made to contact all known survivors and to assess their quality of life using three previously recognised and validated methods. Eighty-three survivors of multiple trauma were discharged but 19 were not studied. Of the remaining 64, 42 patients completed the questionnaire. After multiple trauma, patients reported significant decreases in their quality of life in relation to their overall health, happiness, ability to think and to pursue leisure activities, their income and their employment. Their mean Perceived Quality of Life Score decreased by 13% (95% confidence intervals 7.5-19.5%). Sixty-two percent of survivors experienced severe social disability and a modest or severe impairment at work. The Nottingham Health Profile identified major changes in 'psychological' aspects of quality of life, namely energy and emotional reactions.

Adult↗

Parenterally administered dipeptide alanyl-glutamine prevents worsening of insulin sensitivity in multiple-trauma patients.

BACKGROUND: Dipeptide alanyl-glutamine is a commonly used substrate in major trauma patients. Its importance and effects are widely discussed; as yet, it has not been elucidated whether its administration influences glucose homeostasis. OBJECTIVE: We studied the effect of alanyl-glutamine administration on insulin resistance. DESIGN: Prospective, randomized, controlled trial. SETTING: Intensive care unit of a tertiary level hospital. PATIENTS: Multiple-trauma patients. INTERVENTIONS: Patients were randomized into two groups and assigned to receive parenterally an equal dose of amino acids either with alanyl-glutamine in the dose of 0.4 g x kg body weight(-1) x 24 hrs(-1) (group AG) or without alanyl-glutamine (control group C). This regimen started 24 hrs after injury and continued for 7 days. To assess insulin sensitivity, we performed an euglycemic clamp on day 4 and day 8 after injury. MEASUREMENTS AND MAIN RESULTS: We randomized 40 patients, 20 into each group. At day 4, insulin-mediated glucose disposal was higher in group AG (2.4 +/- 0.7 mg x kg(-1) x min(-1) glucose), with significant difference from group C (1.9 +/- 0.6 mg x kg(-1) x min(-1), p = .044). At day 8, glucose disposal was higher in group AG (2.2 +/- 0.7 mg x kg(-1) x min(-1) glucose), with significant difference in comparison with group C (1.2 +/- 0.6, p < .001). Diminution of the main glucose homeostasis variables in group C between days 4 and 8 of the study was statistically significant (p < .001); however, differences in these variables in group AG were without statistical significance. CONCLUSIONS: Parenteral supplementation of alanyl-glutamine dipeptide was associated with better insulin sensitivity in multiple-trauma patients.

Adult↗

Initial serum ferritin levels in patients with multiple trauma and the subsequent development of acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) represents a catastrophic form of inflammatory lung injury that occurs unpredictably in some, but not all, at-risk patients. In this study, we investigated serum ferritin as a marker for ARDS development in a homogenous group of patients at-risk because of multiple trauma. We hypothesized that since ferritin synthesis is increased by proinflammatory cytokines, which are increased and implicated in ARDS, that ferritin levels would increase and that ferritin increases would correlate with the degree of inflammation and therefore the development of ARDS. We studied 42 patients (25 male, 17 female) who as a consequence of multiple trauma became at-risk for developing ARDS. Using the European/American Consensus definition for ARDS, 16 (38%) patients subsequently developed ARDS (11 male and five female). We found that initial serum ferritin levels correlated with the subsequent development of both ARDS (progression to ARDS, median = 638 ng/ml; (range, 70 to 4,500) versus nonprogression to ARDS = 185 ng/ml; range, 12 to 2,850) (p = 0.02, r = -0.27) and multiple organ failure (p < 0.05, r = 0.39). Using our previously established cutoff points for serum ferritin, the positive predictive value was 62% for men and 75% for women. Initial serum ferritin levels also correlated with a measurement of the degree of initial trauma injury, i.e., the injury severity score (ISS) (p < 0.05, r = 0.37). However, there was no correlation between serum ferritin levels and other markers of clinical injury, namely, lowest PaO2/FIO2 ratio (p = 0.67), days requiring ventilation (p = 0.09), or mortality (p = 0.42). A significant association existed between serum ferritin levels and products of endothelial activation, i.e., sE-selectin (p < 0.04, r = 0.37) and sICAM-1 (p < 0.01, r = 0.21). In the future, with the development of novel anti-inflammatory therapies, early identification of specific high-risk patients would allow the institution of these therapies and thereby increase the chances of reducing ARDS morbidity and mortality.

Acute Disease↗

N-6 polyunsaturated fatty acids confer hemodynamic stability in an experimental model of multiple trauma.

Immunonutrition with diets enriched in polyunsaturated fatty acids (PUFAs) are becoming mandatory for multiple trauma patients. Solutions containing single n-6 PUFAs were administered intravenously in an experimental model of trauma. Thirty-five rabbits were studied; 13 controls; 10 administered gamma-linolenic acid (GLA) 30 min after fracture of the right femor; and 12 arachidonic acid (AA). Systolic, diastolic and mean arterial pressures and heart rate were recorded; serum levels of tumor necrosis factor-alpha (TNFalpha), malondialdehyde (MDA) and nitrate were estimated before and after therapy. Mean survival of controls, of animals treated with GLA and of animals treated with AA was 0.80, 1.41 and 3.60 days, respectively. Administration of PUFAs induced higher levels of blood pressure; that of AA decreased serum TNFalpha and tissue bacterial load compared to controls. Intravenous administration of n-6 PUFAs conferred hemodynamic stability and increased survival in a model of trauma rendering further research mandatory.

Animals↗

[Treatment results in 588 patients with multiple trauma].

BACKGROUND: Ten to fifteen million wounded and 700,000 deaths each year, around the world, are the consequences of accidents, according to the World Health Organization. In Chile 2,269 deaths occur each year due to accidents. The successful treatment of these patients requires a schematized initial management, that is taught in the Advanced Trauma Life Support Course. AIM: To review the results of trauma treatment using this model at Hospital del Trabajador in Santiago. PATIENTS AND METHODS: A retrospective review of patients with trauma treated between 1984 and 1994. The severity of trauma was classified according to the Injury Severity Score. RESULTS: Five hundred eighty eight patients (60 female) aged 35.4 +/- 14 years old were treated in the period. Vehicular accidents accounted for 62% of trauma. The most frequently injured corporal segments were limbs and pelvis in 79%, head and neck in 66% and thorax in 44%. There were 2.45 lesions per patient. Mortality was 8% and, among survivors, 79% had a complete recovery and were reintegrated to their usual activities. Fifteen percent of patients were severely injured. Among these, mortality was 28% and 43% of survivors had some sequel. Head injuries had a predominant role in mortality and post traumatic disabilities. CONCLUSIONS: These results confirm the efficacy of Advanced Trauma Life Support system in the treatment of patients with multiple trauma.

Adolescent↗

[Multiple trauma and burns].

Patients with multiple injuries and burns are the paradigm of critically-ill patients. Their cases are acute, severe and, fortunately, reversible in a large number of situations. The severe aggressions leading to this kind of condition is the rigger for a maelstrom of inflammatory mediators, metabolic and neuro-endocrinal response, leading to an acceleration in the combustion of the injured organ. This "internal combustion" process takes nourishment from organic reserves, using them up and thus producing dysfunctions in various organs. This is where nutritional support has a role, always remedying the metabolic response to inflammation and attempting to modify it. For this reason, nutritional support plays an undisputed part in the treatment of such patients. This nutritional support, so necessary in situations with a high degree of stress, must be individually tailored in terms of quantity and quality to the process and to the patient in question. Thus, adapting the support to requirements appears as a priority of nutritional assessment. While it is important to provide nourishment to needy patients, it is just as important if not more so to avoid over-nourishment. Indirect calorimetry continues to be the most accurate indicator for determining the needs of each patient and, in view of the lack of knowledge of this technique mainly as a result of economic factors, many different methods and formulas have been proposed to attempt to carry out these adjustments. The characteristics and distribution of the macronutrients will be connected with the pathologies to be treated. And finally, the route for providing this nourishment seems ever more clearly to be as prompt first-line administration through the digestive tube. There are situations in which parenteral support will complement or replace the enteral route when the latter is insufficient or unavailable; in certain circumstances, the parenteral route even seems to be superior to enteral support, as in the case of pure head injury. As these patients are particularly prone to suffer from infections, another aspect of increasing interest in the nutritional support of these patients is the use of immunity-modulating diets, where a better response can be expected. The components of the immunity-modulating diets have been shown to be able to modify the immune response in different ways, sometimes favouring the replication of lymphocytes and at other times stimulating the production of certain types of cytokines and attenuating the release of others, in short balancing the inflammatory response.

Burns↗

[Aortic valve insufficiency due to rupture of the cusp in a patient with multiple trauma].

Lesions of the heart valve caused by blunt chest trauma is rare, but when it does occur it can significantly injure the patient. On the basis of autopsy studies, research shows that heart valves are injured in less than 5% of patients who have died due to impact thoracic trauma. Among the heart valves, the aortic valve is the most often lacerated, which has been proved by relevant autopsy and clinical studies. Aortic valve lesions can be the only injury, but it is possible that additional heart or large vessel injuries are also present (myocardial contusion, rupture of the atrial septum, aortic rupture, rupture of the left common carotid artery). The force that causes such an injury is often great and often causes injuries to other organs and organ systems. In a multiple trauma patient, it is very important to specifically look for heart-related injuries because it is possible that they may be overlooked or missed by the surgeon, because of other obvious injuries. We describe the case of a 41-year-old man with multiple trauma who was diagnosed with aortic valve insufficiency due to rupture of the left coronary cusp 6 weeks after a road accident. Valvuloplasty was performed. Seven years later the patient is free of symptoms and is in good physical condition. Echocardiography showed normal dimensions of the heart chambers, a normal thickness of the heart walls, and normal systolic and diastolic function of the left ventricle. Heart valves are morphologically normal, and only an unimportant aortic insufficiency was noticed by echocardiography.

Accidents, Traffic↗

[Traffic multiple trauma patient with head injuries: a study of 146 cases].

146 cases of traffic multiple trauma associated with head injuries were studied. There was a significant difference in the ratio of associated injuries in various parts of the body. The three most encountered parts were chest, shoulder and leg. Death were mainly due to severe head injury, chest injury and shock. Atypical ushing syndrome was due to severe blood loss, even intracranial hypertension existed. The blood pressure decreased rapidly after operation. Since comatous patients were unable to provide chief complaint, misdiagnosis occurred during emergency stage.

Accidents, Traffic↗

Pneumonia in patients with multiple trauma.

This article examines the features of nosocomial pneumonia in the subpopulation of patients with multiple trauma. Epidemiology, trauma-associated risk factors, diagnosis, microbiology, therapy, and prevention are reviewed. While some issues may overlap with critically ill patients in general, differences in approach and management will be discussed.

Anti-Bacterial Agents↗

Delayed diagnosis of thoracolumbar fractures in multiple-trauma patients.

OBJECTIVES: To determine the frequency of delayed diagnosis of major thoracolumbar vertebral fractures (T-L Fxs) in ED multiple-trauma patients, and to determine the differences between cases of delayed and nondelayed diagnoses of T-L Fx. METHODS: A retrospective chart review was conducted of 181 trauma patients with 310 major T-L Fxs (compression, burst, or chance Fxs or dislocations). Data collected included the time of the diagnosis of T-L Fx, the patient's clinical presentation in the ED, the mechanism of injury, and the outcome. RESULTS: Of the 181 patients with major T-L Fxs, 138 were diagnosed in the ED (nondelayed group), and 43 were diagnosed after the patient left the ED (delayed group). Of these, 33 cases occurred in unstable patients requiring emergent medical imaging and/or operation, 7 occurred when emergency physicians failed to detect subtle compression Fxs on ED radiographs, and 3 occurred in stable patients who were not radiographed in the ED. The delayed group were more often critical, and hypotensive, and had lower Glasgow Coma Scale (GCS) scores than did the nondelayed group. The delayed group patients also had more cervical spine injuries, multiple noncontiguous spinal Fxs, high-energy mechanisms of injury, and direct blunt assaults to the back than did the nondelayed group patients. There were 13 patients with T-L Fxs, GCS scores = 15, and normal back examinations. There were 43 patients who had neurologic deficits associated with their injuries; 11 patients with incomplete cord lesions progressed, including 3 in the delayed group. CONCLUSIONS: A delay in the diagnosis of T-L Fx in hospitalized trauma patients is frequently associated with an unstable patient condition that necessitates higher-priority procedures than ED T-L spine radiographs. Such patients should receive spinal precautions until more complete evaluation can be performed. The decision to selectively radiograph T-L spines in multiple-trauma patients should consider the mechanism of injury, the presence of possible confounders to physical examination, and clinical signs and symptoms of back injury.

Adolescent↗

Guideline validation in multiple trauma care through business process modeling.

Clinical guidelines can improve the quality of care in multiple trauma. In our Department of Trauma Surgery a specific guideline is available paper-based as a set of flowcharts. This format is appropriate for the use by experienced physicians but insufficient for electronic support of learning, workflow and process optimization. A formal and logically consistent version represented with a standardized meta-model is necessary for automatic processing. In our project we transferred the paper-based into an electronic format and analyzed the structure with respect to formal errors. Several errors were detected in seven error categories. The errors were corrected to reach a formally and logically consistent process model. In a second step the clinical content of the guideline was revised interactively using a process-modeling tool. Our study reveals that guideline development should be assisted by process modeling tools, which check the content in comparison to a meta-model. The meta-model itself could support the domain experts in formulating their knowledge systematically. To assure sustainability of guideline development a representation independent of specific applications or specific provider is necessary. Then, clinical guidelines could be used for eLearning, process optimization and workflow management additionally.

Humans↗

Guideline validation in multiple trauma care through business process modeling.

Clinical guidelines can improve the quality of care in multiple trauma. In our Department of Trauma Surgery a specific guideline is available paper-based as a set of flowcharts. This format is appropriate for the use by experienced physicians but insufficient for electronic support of learning, workflow and process optimization. A formal and logically consistent version represented with a standardized meta-model is necessary for automatic processing. In our project we transferred the paper-based into an electronic format and analyzed the structure with respect to formal errors. Several errors were detected in 7 error categories. The errors were corrected to reach a formal and logically consistent process model. In a second step the clinical content of the guideline was revised interactively using a process modeling tool. Our study reveals that guideline development should be assisted by process modeling tools, which check the content in comparison to a meta-model. The meta-model itself could support the domain experts in formulating their knowledge systematically. To assure sustainability of guideline development a representation independent of specific applications or specific provider is necessary. Then clinical guidelines could be used for training, process optimization and workflow management additionally.

Germany↗

Efficiency of chest computed tomography in critically ill patients with multiple traumas.

OBJECTIVE: The efficiency of secondary thoracic computed tomography (TCT) in critically ill patients with multiple traumas was assessed by comparison of TCT with chest radiograph findings. The subsequent therapeutic consequences based on the additional information of TCT were evaluated. SETTING: A six-bed trauma intensive care unit in a university hospital. DESIGN: Prospective, descriptive study. PATIENTS AND INTERVENTIONS: One hundred one computed tomographic (CT) examinations (mean, 2.6 per patient; range, 1-10) were performed in 39 patients, fulfilling the following indications for TCT: a) sepsis with suspected pulmonary focus (n = 41); b) deterioration of pulmonary gas exchange (n = 35); c) guiding the duration of intermittent prone positioning (n = 25). The information provided by TCT was compared with corresponding chest radiographs (CXR). Therapeutic consequences drawn after TCT were compared with the additional diagnostic information of TCT. The change of therapy was documented that would not have been undertaken or may have been delayed had TCT evaluation not been used. RESULTS: TCT was significantly superior to CXR in detecting pneumothoraces, pleural effusions, and pulmonary abscesses. Furthermore, a significantly higher accuracy regarding pulmonary densities was found. Subsequent therapeutic interventions ensued from 85 (84.2%) CT scans. After TCT, intermittent prone positioning was initiated in 31 patients, chest tubes were inserted in 16 patients, and intermittent prone positioning was terminated in 13 patients and was continued in 12 patients. Eleven thoracotomies were performed because of the TCT findings. The described therapeutic interventions were based on abnormalities seen on CT scans but were not evident in CXR in 58 patients (57.4%). Significant information that influenced therapeutic concepts was obtained in 66% (n = 23) of patients with pulmonary deterioration of gas exchange, in 61% (n = 25) of patients with sepsis, and in 40% (n = 10) of patients to guide the duration of intermittent prone positioning. Thoracotomy and specific drainage by tube thoracostomy was always dependent on the findings of TCT. CONCLUSION: Performed under the above displayed defined indications, TCT had an overall efficiency of 57%. It provided an increased sensitivity for intrathoracic lesions and a more comprehensive diagnosis of chest abnormalities.

Adolescent↗

Multiple trauma and scapula fractures: so what?

UNLABELLED: BACKGROUND Scapula fractures are rare and are presumed to indicate severe underlying trauma. We studied injury patterns and overall outcome in patients with multiple injuries with scapula fractures. METHODS: We carried out a retrospective review of patients with multiple injuries (Injury Severity Score [ISS] > or = 16) with chest and musculoskeletal injuries admitted to our institution between 1993 and 1999 to investigate whether the presence of a scapula fracture is a marker of increased morbidity and mortality. RESULTS: There were 1,164 patients admitted with multiple trauma. Seventy-nine (6.8%) of the 1,164 sustained a scapula fracture, forming the study group. The remainder of the patients (n = 1,085) formed the control group of the study. Both groups of patients were similar with regard to age and Glasgow Coma Scale score (age, 42 +/- 17.8 [+/- SD] vs. 40 +/- 22; GCS score, 11.2 +/- 5.1 vs. 11 +/- 5 in the study and control groups, respectively). The overall ISS was significantly higher in those with scapula fractures (27.12 +/- 15.13 vs. 22.8 +/- 14.4, p = 0.01). Patients with scapula fractures also had more severe chest injuries (Abbreviated Injury Scale score of 3.46 +/- 1.1 vs. 3.1 +/- 1.0, respectively), but not significantly so. However, the incidence of rib fractures was significantly higher in the patients with scapula fractures (p < 0.05). The incidence and severity of head and abdominal injuries were similar in the two groups. The severity of extremity injuries in patients with scapula fractures was significantly lower (2.4 +/- 0.6 vs. 2.7 +/- 0.7, p = 0.001). The rate of admission, the length of intensive care unit stay, and the overall length of hospital stay were similar in the two groups. The overall mortality rate was 11.4% in patients with scapula fractures and 20% in those without scapula fractures (p = 0.1). CONCLUSION: Patients with scapula fractures have more severe underlying chest injuries and overall ISS. However, this did not correlate with a higher rate of intensive therapy unit admission, length of hospital stay, or mortality.

Abbreviated Injury Scale↗