Derivation of a prediction rule for posttraumatic organ failure using plasma DNA and other variables.

The early identification of patients at high risk of developing posttraumatic organ failure would allow preventive therapies to be studied. In this study, highly sensitive and specific guidelines for the early prediction of posttraumatic organ failure (OF) and multiple organ dysfunction syndrome (MODS) using cell-free (plasma) DNA and other predictors of posttraumatic complications were derived. As plasma DNA increases after injury and may be used to predict acute lung injury (ALI), we hypothesized that in combination with other predictors it would predict the later development of OF and MODS. Eighty-three patients (69 males; median age, 36 years) were studied as a consequence of major trauma within 3.5 hours of injury (median time to sampling and assessment, 60 min). Plasma DNA was measured using a real-time, quantitative, polymerase chain reaction assay for the beta-globin gene. OF and MODS occurred in 20/83 (24%) and 9/79 (11%) cases, respectively. At selected cutoff points, the sensitivity of plasma DNA for predicting OF and MODS ranged from 50% to 100%, specificity ranged from 74% to 95%, and the likelihood ratio ranged from 3.89 to 10.50. Other variables studied included serum albumin, creatine kinase, aspartate transaminase, lactate dehydrogenase, leukocyte count, hematocrit, injury severity score, maximal abbreviated injury score, and shock index. Using a classification and regression tree, plasma DNA and aspartate transaminase at optimal cutoffs predicted OF and MODS with an overall correct classification of 93% and 87%, respectively.

Role of monocyte L-selectin in the development of post-traumatic organ failure.

The vascular leucocyte adhesion molecule, L-selectin, plays an important early role in monocyte trafficking at sites of inflammation, a process which leads to the development of inflammatory organ failure. In this prospective observational study, we investigate whether early numerical and functional changes in circulating monocytes, expression of monocyte L-selectin (CD62L) and monocyte:neutrophil L-selectin ratios are related to the subsequent development of post-traumatic organ failure (OF) and multiple organ dysfunction syndrome (MODS). Monocyte counts and cell surface L-selectin were measured by an automated cell counter and flow cytometry, respectively. Of 164 trauma patients admitted to a university emergency department resuscitation room, 64 had multiple injuries, 51 developed OF, 20 developed MODS and 21 died. Early monocyte counts in patients with multiple injuries were lower in those who developed MODS (0.44 x 10(9)/l) compared with those who did not (0.60 x 10(9)/l; P=0.024). Monocyte L-selectin mean channel fluorescence increased with injury severity and was highest in those who developed MODS (P=0.033). In the sub-group of patients with multiple injuries, L-selectin mean channel fluorescence was also greater in those patients who developed MODS compared with patients who did not develop MODS (P=0.042). The monocyte to neutrophil count ratio also decreased with injury severity (P=0.006). Using optimal cut off values for L-selectin mean channel, fluorescence, the positive and negative predictive values for OF was 43.5 and 91.4%, respectively and for MODS it was 25.4 and 92.9%, respectively. Alterations in early circulating monocyte counts and L-selectin expression after injury are related to the development of post-traumatic organ failure and suggest an area in the inflammatory pathway that may be influenced by L-selectin blockade.

Community-acquired pneumonia--implementation of a prediction rule to guide selection of patients for outpatient treatment.

The aim of this study was to determine the outcomes of outpatient treatment of community-acquired pneumonia (CAP) when a prediction rule was followed by emergency physicians to guide the selection of patients. This was a prospective observational study conducted at the emergency department of a university-affiliated hospital in Hong Kong, China. A clinical prediction rule was implemented to guide the selection of patients with CAP for outpatient treatment. All subsequent hospitalizations gial presentation were recorded, and the reasons were assessed. The utilization of the observation unit was incorporated into the treatment algorithm. Of 72 patients with CAP followed up as outpatients, 60 (83.3%) were treated successfully, nine (12.5%) required subsequent hospitalization within 30 days, and three (4.2%) were lost to follow-up. None of the patients died, and none required admission to the intensive care unit. Factors associated with subsequent hospitalization include: tuberculosis, underlying malignancy, persistent fever, comorbidity (rheumatoid arthritis and severe osteoporosis), intravenous drug addiction and alcoholism. The observation ward was utilized in 10 (16.7%) patients successfully treated as outpatients. It is concluded that the prediction rule can be safely implemented as a guide for emergency physicians. The short-stay observation unit may be usefully employed for treating low-risk CAP.

Cost effectiveness analysis of intravenous ketorolac and morphine for treating pain after limb injury: double blind randomised controlled trial.

OBJECTIVES: To investigate the cost effectiveness of intravenous ketorolac compared with intravenous morphine in relieving pain after blunt limb injury in an accident and emergency department. DESIGN: Double blind, randomised, controlled study and cost consequences analysis. SETTING: Emergency department of a university hospital in the New Territories of Hong Kong. PARTICIPANTS: 148 adult patients with painful isolated limb injuries (limb injuries without other injuries). MAIN OUTCOME MEASURES: Primary outcome measure was a cost consequences analysis comparing the use of ketorolac with morphine; secondary outcome measures were pain relief at rest and with limb movement, adverse events, patients' satisfaction, and time spent in the emergency department. RESULTS: No difference was found in the median time taken to achieve pain relief at rest between the group receiving ketorolac and the group receiving morphine, but with movement the median reduction in pain score in the ketorolac group was 1.09 per hour (95% confidence interval 1.05 to 2.02) compared with 0.87 (0.84 to 1.06) in the morphine group (P=0.003). The odds of experiencing adverse events was 144.2 (41.5 to 501.6) times more likely with morphine than with ketorolac. The median time from the initial delivery of analgesia to the participant leaving the department was 20 (4.0 to 39.0) minutes shorter in the ketorolac group than in the morphine group (P=0.02). The mean cost per person was $HK44 ( pound4; $5.6) in the ketorolac group and $HK229 in the morphine group (P<0.0001). The median score for patients' satisfaction was 6.0 for ketorolac and 5.0 for morphine (P<0.0001). CONCLUSION: Intravenous ketorolac is a more cost effective analgesic than intravenous morphine in the management of isolated limb injury in an emergency department in Hong Kong, and its use may be considered as the dominant strategy.

Early role of neutrophil L-selectin in posttraumatic acute lung injury.

OBJECTIVE: To investigate whether early numerical and functional changes in circulating neutrophils and expression of neutrophil L-selectin and soluble L-selectin are related to the subsequent development of posttraumatic acute lung injury (ALI), the systemic inflammatory response syndrome, sepsis, and organ failure. DESIGN: Prospective study of whole blood and plasma samples to assess numerical and functional changes in circulating neutrophils and in soluble L-selectin. SETTING: The emergency department of a university hospital. PATIENTS: A total of 147 patients admitted to the resuscitation room after trauma were compared with 69 control subjects. Ten patients developed ALI. LABORATORY ANALYSIS: Flow cytometry of whole blood and ELISA of plasma. RESULTS: Total leukocyte and neutrophil counts, expression of L-selectin, and the ratio of neutrophil to plasma L-selectin increased with injury and were highest in those who developed ALI. Soluble L-selectin decreased with injury severity and was lowest in those who developed ALI. CONCLUSIONS: Early changes in the average expression of L-selectin per cell do not correlate with the development of subsequent posttraumatic ALI. However, the development of ALI is related to the total expression of L-selectin in the neutrophil mass, and the most striking association is in those with lower concentrations of plasma L-selectin.

Increased plasma free cyclic-AMP levels following major trauma and their relevance to the immune response.

BACKGROUND: Following injury, neutrophil mobilisation is an important element of the immune response. The ideal features of an agent responsible for this mobilisation would include the ability to mobilise neutrophils without activating them, and rapid reversibility. This study investigates the hypothesis that raised levels of plasma adrenaline following trauma act via cyclic adenosine monophosphate (cAMP) to mobilise neutrophils, and measures the amount of cAMP extruded from cells into the plasma following injury. METHODS: 20-ml samples of venous blood were drawn from 34 trauma patients within 3 h of injury and divided between three sample tubes: (1) ethylene diamine tetra-acetic acid anticoagulant (EDTA) for full blood count; (2) cooled EDTA for cAMP levels; and (3) cooled lithium heparin for catecholamines. The latter two tubes were immediately centrifuged at low temperature and the supernatant plasma deep frozen pending analysis. Adrenaline was measured using high pressure liquid chromatography (HPLC) and cAMP measured by an enzyme immunoassay technique. RESULTS: 34 patients, six of whom had sustained minor trauma (ISS 1-8), 12 moderate trauma (ISS 9-15) and 16, major trauma (ISS 16 and above) were studied. Median age was 39 years (range 16-77) and 30 patients were male. Plasma adrenaline levels were available for 28 of the patients. Plasma free cAMP levels were significantly raised in patients with major trauma (P < 0.006). There were positive correlations between the plasma levels of cAMP and adrenaline (rho 0.660, P = 0.011), adrenaline and neutrophil count (rho 0.654, P = 0.01) and cAMP and neutrophil count (rho 0.508, P = 0.013). CONCLUSIONS: Evidence is presented of the possible inter-relationships between neutrophil counts, adrenaline levels and cAMP levels following injury, supporting the proposition that neutrophil mobilisation pathways are activated early via beta-adrenergic stimulation.

Plasma DNA as a prognostic marker in trauma patients.

BACKGROUND: Recently, much interest has developed in the potential use of plasma DNA as a diagnostic and monitoring tool. We hypothesized that plasma DNA is increased in patients with trauma and may be prognostic in such patients. METHODS: We studied 84 patients who had sustained an acute blunt traumatic injury. We measured plasma DNA by a real-time quantitative PCR assay for the beta-globin gene. Blood samples were collected at a median time of 60 min following injury. Blood samples were also obtained from 27 control subjects. RESULTS: The median plasma DNA concentrations in the control, minor/moderate trauma (Injury Severity Score <16; n = 47), and major trauma (Injury Severity Score > or =16; n = 37) groups were 3154 kilogenome-equivalents/L, 13 818 kilogenome-equivalents/L, and 181 303 kilogenome-equivalents/L, respectively. Plasma DNA concentrations in patients with adverse outcomes, including acute lung injury, acute respiratory distress syndrome, and death, had 11. 6- to 12-fold higher plasma DNA concentrations than those who did not develop these complications. At a cutoff of 232 719 kilogenome-equivalents/L, the sensitivities of plasma DNA analysis for the prediction of acute lung injury, acute respiratory distress syndrome, and death were 100% (95% confidence interval, 100-100%), 100% (95% confidence interval, 100-100%), and 78% (95% confidence interval, 40-97%), respectively. The respective specificities were 81% (95% confidence interval, 71-89%), 80% (95% confidence interval, 70-88%), and 82% (95% confidence interval, 71-90%). CONCLUSIONS: Plasma DNA is increased after trauma and may be a potentially valuable prognostic marker for these patients.

Sonography compared with radiography in revealing acute rib fracture.

OBJECTIVE: This study was undertaken to compare the sensitivities of sonography and radiography for revealing acute rib fracture. SUBJECTS AND METHODS: Chest radiography and rib sonography were performed on 50 patients with suspected rib fractures. Sonography was performed with a 9- or 12-MHz linear transducer. Fractures were identified by a disruption of the anterior margin of the rib, costochondral junction, or costal cartilage. The incidence, location, and degree of displacement of fractures revealed by radiography and sonography were compared. Sonography was performed again after 3 weeks in 37 subjects. RESULTS: At presentation, radiographs revealed eight rib fractures in six (12%) of 50 patients and sonography revealed 83 rib fractures in 39 (78%) of 50 patients. Seventy-four (89%) of the 83 sonographically detected fractures were located in the rib, four (5%) were located at the costochondral junction, and five (6%) in the costal cartilage. Repeated sonography after 3 weeks showed evidence of healing in all reexamined fractures. Combining sonography at presentation and after 3 weeks, 88% of subjects had sustained a fracture. CONCLUSION: Sonography reveals more fractures than does radiography and will reveal fractures in most patients presenting with suspected rib fracture. Further scientific studies are needed to clarify the appropriate role for sonography in rib fracture detection.

Do peripheral blood counts have any prognostic value following trauma?

BACKGROUND: Both lymphocytosis and lymphopenia have been observed following trauma and each has been claimed to predict mortality. An understanding of the early temporal changes in leucocyte counts may help to explain why such discrepancies have been found. The purpose of this study was to determine the early serial changes in peripheral leucocyte counts following injury. METHODS: A whole blood cell counter was used to measure serial total leucocyte, granulocyte, lymphocyte and monocyte counts from 20 patients in the first 3 h following blunt injury. Four to six peripheral blood samples were taken from each subject and grouped into 20 min intervals. RESULTS: Granulocytosis, lymphocytosis and monocytosis were evident within 40 min of injury. A biphasic granulocyte and monocyte response was observed in the first 3 h following trauma. Lymphocytes showed a linear resolution towards normal (regression coefficient -0.022; p < 0.01) with some individuals developing a lymphopenia. No correlation with injury severity was observed. CONCLUSION: Rapid mobilisation and subsequent redistribution of leucocytes occurs early following injury. Temporal changes will affect any predictive value of circulating leucocytes and studies must be precise with respect to blood sampling time.

Derivation of a prediction rule for post-traumatic acute lung injury.

The purpose of this study was to derive an early, highly sensitive and specific prediction rule for the development of post-traumatic acute lung injury (ALI). In a prospective, non-interventional study a convenience sample of 92 adults admitted to the resuscitation room following blunt trauma was studied in order to derive this prediction rule. The study was conducted in the emergency department of a university hospital in the New Territories of Hong Kong. One emergency physician assessed each patient for 25 variables, which might predict post-traumatic ALI, and the primary outcome measure was the presence or absence of ALI 48 h post-injury. Eleven variables associated with ALI were entered into a classification and regression tree (CART) in order to derive models predictive of ALI. Two models were developed and used to derive the decision rule. Acute lung injury was likely if either: (1) the patient had an ISS > 27 and a haematocrit < 0.37, or (2) the patient had a haematocrit < 0.36 and a total leucocyte count > 15. The first guideline had a classification rate of 96.7% (95% confidence interval (CI), 90.8-99.3%), a sensitivity of 100% (CI 65.2-100%) and a specificity of 96.5% (CI 90.0-99.3%). The second guideline had a classification rate of 96.7% (CI 90.8-99.3%), a sensitivity of 85.7% (CI 42.1-99.6%) and a specificity of 97.7% (CI 91.8-99.7%). Practical highly sensitive and specific prediction guidelines for post-traumatic acute lung injury have been derived and now require prospective validation.

Adrenaline upregulates monocyte L-selectin in vitro.

OBJECTIVE: Although surface adhesion molecules mediate leucocyte-endothelial interactions at sites of inflammation, relatively little is known of the factors which increase the expression of L-selectin in circulating leucocytes. The expression of leucocyte L-selectin increases during acute stress events such as injury and is temporally related to an early neuroendocrine response. This study investigates whether adrenaline increases the expression of L-selectin on monocytes, neutrophils and lymphocytes in vitro and whether these effects are mediated via beta-adrenoceptors. METHODS: A total of 20 ml of blood was withdrawn from 28 healthy volunteers (21 males) with a mean age of 29 years (range 23-67 years). Adrenaline at physiological doses mimicking trauma (0-200 nmol/l) was added to whole blood prior to immunofluorescent staining and analysis by flow cytometry. Propranolol (50 microl of 2 x 10(-5) M) was also added to separate tubes prior to incubation with adrenaline. Saline (40 microl 0.9% solution) was used as a control. Expression is described firstly as percentage of cells expressing L-selectin and secondly as average intensity (mean channel fluorescence, mcf) per cell expressing CD62L. Summary measures were used to analyse the data. RESULTS: A significant increase in both the percentage of monocytes expressing L-selectin and mean channel fluorescence of L-selectin was evident with adrenaline in vitro (P < 0.0001). Maximal increases occurred at 100 nmol/l adrenaline when a 9% increase in the percentage of monocytes expressing L-selectin and a 23% increase in mean channel fluorescence were observed. These effects were both blocked by propranolol (P < 0.0001). No significant differences were observed for neutrophils or lymphocytes except for a slight increase in the percent neutrophils expressing L-selectin, and a small decreasing trend in percent lymphocytes expressing L-selectin. CONCLUSIONS: Adrenaline upregulates the surface expression of L-selectin on monocytes in vitro, an effect which is partially mediated by beta-adrenoceptors. As monocytes initiate early aspects of the inflammatory response, these findings suggest that beta-blockade may have an inhibitory role for certain aspects of leucocyte trafficking.

Leukocyte L-selectin is up-regulated after mechanical trauma in adults.

BACKGROUND: Infection and multiple organ failure remain the principal causes of late mortality after trauma despite advances in the resuscitation of injured patients. Because a better understanding of postinjury leukocyte trafficking is essential to the development of possible therapeutic measures aimed at preventing these complications, we have performed a study of one factor in the early posttrauma endothelial adhesion behavior of monocytes, lymphocytes, and neutrophils: their cell surface expression of L-selectin (CD62L). We have also studied the plasma levels of soluble L-selectin in these patients. METHODS: Two venous blood samples were taken from each of 41 trauma patients at median times of 1 and 20 hours after injury. The study group included 16 patients with major (Injury Severity Score (ISS) > or = 16), 17 with moderate (ISS = 9-15), and 8 with minor (ISS < 9) trauma. Cell surface L-selectin was measured on leukocyte subsets by staining with specific fluorescent-labeled monoclonal antibodies to CD62L and using flow cytometry. Both the percentage of cells expressing the molecule and the mean channel fluorescence were measured. Levels of soluble L-selectin were measured in the plasma, sampled concurrently, by enzyme-linked immunosorbent assay. RESULTS: Monocytes, lymphocytes, and neutrophils all showed an early increase in cell surface L-selectin expression as measured by mean channel fluorescence (p < 0.0001, p < 0.001, and p < 0.0001, respectively), and this persisted in later samples taken at a median 20 hours after injury (p < 0.0001,p < 0.0001, and p < 0.01). Only monocytes showed an increased percentage of cells expressing the molecule in the early phase (p < 0.02), and this remained in the later phase (p < 0.001). Monocytes also showed a further significant increase in mean channel fluorescence (p < 0.02) between the two periods. No significant changes in levels of plasma soluble L-selectin were found at either stage. CONCLUSION: An increase in the expression of L-selectin on each of three leukocyte populations has been demonstrated in the early phase after trauma. This would tend to promote rolling behavior of leukocytes and increase their contact with the vascular endothelium. There were marked differences in the later responses of the three populations, which may represent differential control of their behavior.

The flat electrocardiogram--systole or asystole?

A case of stone heart syndrome is reported in a pregnant 27 year old West African patient, who suffered syncopal symptoms shortly before cardiac arrest. The electrocardiographic features were those of asystole, but direct examination of the heart at emergency thoracotomy in the A&E department revealed tetanic contracture of the organ. At necropsy, the heart was of normal weight but showed areas of fibrosis surrounding the bundle of His. The discrepancy between the ECG features and the physiological state of the heart raises the possibility that other cases of apparent asystole may not be what they seem.

Alteration in leukocyte adhesion molecule expression following minor, moderate and major trauma.

An understanding of the mechanisms of post-injury leukocyte trafficking is essential to the development of future therapeutic interventions aimed at preventing infection and multiple organ failure in trauma patients, yet very little is known about the cellular and molecular events resulting in mobilization of members of the leukocyte family following trauma. We have studied the post-injury expression of the lymphocyte, monocyte and neutrophil adhesion molecules CD11a (LFA-1), CD11b, CD11c, CD29 (beta-1 integrin) and CD62L (L-selectin) in a group of 36 trauma patients, 13 of whom had suffered major trauma (ISS > or = 16), 15 moderate trauma (ISS = 9-15) and eight minor trauma (ISS < 9). Three ml blood samples were taken within 2.5 h of injury (mean sample time = 1.2 h, median = 1 h) into EDTA anticoagulant. Fifty-three normal control subjects were also studied for comparison. Leukocytes were stained using fluorescent-labelled monoclonal antibodies specific for each adhesion molecule, and the mean receptor density per cell measured using flow cytometry. Monocytes, neutrophils and lymphocytes in the trauma patients showed significantly increased mean-receptor density of L-selectin (p < 0.0001, 0.0001 and 0.004 respectively). Neutrophils and monocytes showed a significantly decreased level of expression of CD11a, and neutrophils showed a significant decrease in expression of CD11c. Our results indicate that there is a reduction in CD11a expression after trauma which may play an important role in the demargination of neutrophils and monocytes. The strong increase in L-selectin expression in all cell populations was unexpected, and is potentially important because this molecule supports rolling behaviour in all members of the leukocyte family, and would promote close contact between leukocytes and the endothelium at the site of injury without firm adhesion taking place. These events may be of significance in planning future strategies to combat post-trauma complications.