https://heeoe.hee.nhs.uk/sites/default/files/130220p_whole_body_ct.pdf

Effect of whole-body CT during trauma resuscitation on survival: a retrospective, multicentre study

Summary Background There is increasing evidence for acute traumatic coagulopathy occurring prior to emergency room (ER) admission but detailed information is lacking. Patients and methods A retrospective analysis using the German Trauma Registry database including 17,200 multiple injured patients was conducted to determine (a) to what extent clinically relevant coagulopathy has already been established upon ER admission, and whether its presence was associated (b) with the amount of intravenous fluids (i.v.) administered pre-clinically, (c) with the magnitude of injury, and (d) with impaired outcome and mortality. Eight thousand seven hundred and twenty-four patients with complete data sets were screened. Results Coagulopathy upon ER admission as defined by prothrombin time test (Quick's value) −1 , was present in 34.2% of all patients. There was an increasing incidence for coagulopathy with increasing amounts of i.v. fluids administered pre-clinically. Coagulopathy was observed in >40% of patients with >2000ml, in >50% with >3000ml, and in >70% with >4000ml administered. Ten percentage of patients presented with clotting disorders although pre-clinical resuscitation was limited to 500ml of i.v. fluids maximum. The mean ISS score in the coagulopathy group was 30 (S.D. 15) versus 21 (S.D. 12) ( p p p p Conclusion There is a high frequency of established coagulopathy in multiple injury upon ER admission. The presence of early traumatic coagulopathy was associated with the amount of intravenous fluids administered pre-clinically, magnitude of injury, and impaired outcome.

Early coagulopathy in multiple injury: An analysis from the German Trauma Registry on 8724 patients

Within minutes of a traumatic impact, a robust inflammatory response is elicited in the injured brain. The complexity of this post-traumatic squeal involves a cellular component, comprising the activation of resident glial cells, microglia, and astrocytes, and the infiltration of blood leukocytes. The second component regards the secretion immune mediators, which can be divided into the following sub-groups: the archetypal pro-inflammatory cytokines (Interleukin-1, Tumor Necrosis Factor, Interleukin-6), the anti-inflammatory cytokines (IL-4, Interleukin-10, and TGF-beta), and the chemotactic cytokines or chemokines, which specifically drive the accumulation of parenchymal and peripheral immune cells in the injured brain region. Such mechanisms have been demonstrated in animal models, mostly in rodents, as well as in human brain. Whilst the humoral immune response is particularly pronounced in the acute phase following Traumatic brain injury (TBI), the activation of glial cells seems to be a rather prolonged effect lasting for several months. The complex interaction of cytokines and cell types installs a network of events, which subsequently intersect with adjacent pathological cascades including oxidative stress, excitotoxicity, or reparative events including angiogenesis, scarring, and neurogenesis. It is well accepted that neuroinflammation is responsible of beneficial and detrimental effects, contributing to secondary brain damage but also facilitating neurorepair. Although such mediators are clear markers of immune activation, to what extent cytokines can be defined as diagnostic factors reflecting brain injury or as predictors of long term outcome needs to be further substantiated. In clinical studies some groups reported a proportional cytokine production in either the cerebrospinal fluid or intraparenchymal tissue with initial brain damage, mortality, or poor outcome scores. However, the validity of cytokines as biomarkers is not broadly accepted. This review article will discuss the evidence from both clinical and laboratory studies exploring the validity of immune markers as a correlate to classification and outcome following TBI.

/pdf/the-role-of-markers-of-inflammation-in-traumatic-brain-2mhki7d04s.pdf

The role of markers of inflammation in traumatic brain injury.

Anaphylaxis

Objective The use of corticosteroids in patients with sepsis or septic shock has been controversial for many decades. Clinical studies have reported beneficial, as well as negative results. We conducted a meta-analysis to assess the clinical evidence and to evaluate treatment effects in specific sub

Steroid controversy in sepsis and septic shock: a meta-analysis.

In 2 clinical studies in 40 conscious human volunteers and 164 orthopedic patients histamine-release responses were diagnosed, defined and classified. Polygeline (Haemaccel) in its now outdated formulation [40] was chosen as a clinical histamine releaser. The main interest was not concentrated on the extreme, the “classical” anaphylactic response, but on theaverage histamine-release response found in clinical experiments with so many drugs in the last 10 years. In human volunteers 600 ng/kg histamine was i. v. injected. Indicants for a systemic anaphylactoid reaction with the highest incidence ratio were tachycardia, plasma histamine levels >1 ng/ml, “metallic taste”, flush, congestion of head, “wet eyes” and tears, hypertension and headache. Following polygeline none of these subjects developed a life-threatening reaction, but 12 showed a systemic response, 11 a cutaneous reaction and 17 were non-responders. Indicants for a systemic anaphylactoid reaction with the highest incidence ratio were plasma histamine levels >1 ng/ml, tachycardia, wheals, sensation of heat, narrowness of throat, hypertension, headache and wet eyes or tears. In a prolective, cohort study in the orthopedic patients 3 subjects with life-threatening reactions, 27 with systemic response, 96 with cutaneous reaction and 38 non-responders were included. Indicants with the highest incidence ratio were tachycardia, plasma histamine levels >1 ng/ml, erythema and wheals, cough, flush, stuffy nose and facial oedema. With this trial the indicants for diagnosing a systemic histamine release response in volunteers were validated in patients to a large extent. Thus the average histamine-release response was defined by clinical signs such as tachycardia and mild hypertension, scattered hives such as spots of erythema and wheals, respiratory symptoms in the laryngeal and nasal region, such as cough, narrowness in the throat, stuffy nose and sneezingand by pathological plasma histamine levels (>1 ng/ml). In addition histamine-release responses were differentiated as cutaneous responses, systemic responses and life-threatening responses by clinical and operational criteria and by plasma histamine levels. Using clinical trials and medical decision making procedures the incidence of systemic histamine-release responses in patients higher by two orders of magnitude than in other studies reported hitherto.

/pdf/definition-and-classification-of-the-histamine-release-5dyv2reifp.pdf

Definition and Classification of the Histamine-Release Response to Drugs in Anaesthesia and Surgery: Studies in the Conscious Human Subject* **

Das Traumaregister der Deutschen Gesellschaft für Unfallchirurgie

Zum Zeitpunkt der Krankenhausaufnahme werden zahlreiche Variablen beim schwerverletzten Patienten erhoben. Die Wertigkeit dieser Variablen in Bezug auf ihre Fahigkeit der Prognoseabschatzung wird unterschiedlich beurteilt. Ziel ist es, bei Krankenhausaufnahme eine initiale Abschatzung des Outcomes schwerverletzter Patienten vornehmen zu k¨nnen. Dazu wurde ein multivariates Prognosemodell auf der Grundlage des Traumaregisters der DGU entwickelt. Patienten und Methode. Zum Zeitpunkt der Krankenhausaufnahme werden durch das DGU-Traumaregister mehr als 30 Variable prospektiv erfasst. Im 1. Schritt der zentral anonymisierten Auswertung wurden zur Vermeidung multipler statistischer Vergleiche diejenigen Variablen ausgewahlt, die aufgrund der Literatur als klinische Pradiktoren fur das Outcome angesehen werden. Im 2. Schritt erfolgte eine univariate Analyse dieser Variablen. Fur alle primaren Variablen mit univariater Signifikanz der Outcomevorhersage wurde im 3. Schritt, eine multivariate logistische Regression durchgefuhrt und ein multivariates Prognosemodell entwickelt. Ergebnisse. Vom 01.01.1993 bis 31.12.1997 wurden 2069 Patienten aus 20 Kliniken im Traumaregister prospektiv erfasst (Alter 39±19 Jahre; m.: 70,0%; ISS 22±13; 18,6% verstorben). Aus mehr als 30 bei Aufnahme erhobenen Variablen zeigten sich das Alter, der GCS, der ISS, der Base-Excess (BE) und der Quick-Wert als wichtigste Prognosefaktoren zur Abschatzung der Wahrscheinlichkeit zu versterben [P(Tod)]. Folgendes Prognosemodell wurde entwickelt: P(Tod)=1/1+e{−[k+β1(Alter)+β2(GCS)+β3(ISS)+β4(BE)+β5(Quick)]} wobei: k=−0,1551, β1=0,0438 mit p<0,0001, β2=−0,2067 mit p<0,0001, β3=0,0252 mit p=0,0071, β4=−0,0840 mit p<0,0001 und β5=−0,0359 mit p−0,0001. Jedes der 5 Variablen tragt signifikant zu dieser multifaktoriellen Gleichung bei. Schlussfolgerungen. Diese Daten zeigen, dass initiales Alter, GCS, ISS, Base-Excess und Quick-Wert fruhzeitig verfugbare und potentiell wichtige Pradiktoren sind, um Traumapatienten mit einer hohen Sterbenswahrscheinlichkeit zu identifizieren. Mit Hilfe von Base-Excess und Quick-Wert, als einzige beeinflussbare Variablen dieser multifaktoriellen Gleichung, kann moglicherweise die fruhzeitige, aggressive Therapie besser gesteuert werden.

[Predicting the outcome in severe injuries: an analysis of 2069 patients from the trauma register of the German Society of Traumatology (DGU)].

Histamine release by drugs used in anaesthesia and surgery has been often demonstrated in human volunteers, but only occasionally in patients. Three questions arose from these studies. (1) Is the incidence of histamine release high in patients during routine anaesthesia and surgery? (2) Can the clinical effects of histamine release in man be prevented by H1+H2-receptor antagonists? (3) Are there any side-effects of such a premedication? These problems were investigated in patients and volunteers by randomized controlled clinical trials using only one of the histamine-liberating drugs in man, the plasma substitute Haemaccel. This drug was chosen because it causes a reproducible histamine release in man and because its mechanism of action in man is largely known.

(1)

Out of 600 orthopaedic patients 30 (5%) showed anaphylactoid reactions following Haemaccel infusion. 26 of these had a histamine release of more than 1 ng histamine/ml plasma. Using predictive values this gives an efficiency of the test by nearly 98%.




(2)

In volunteers the combination of an H1-plus H2-receptor antagonist (dimethpyrindene and cimetidine) completely prevented the clinical effects of histamine release by Haemaccel (9 allergoid and anaphylactoid reactions in the control group, none in the H1+H2-group). The incidence of histamine release, however, remained unchanged.




(3)

The premedication was found to release histamine itself. Cimetidine was effective when given alone but especially in combination with chlorpheniramine (4 events out of 7 applications). The clinical side-effects of these premedication were mild since apparently the free histamine was largely blocked at the receptor sites.

H1 + H2-receptor antagonists for premedication in anaesthesia and surgery: a critical view based on randomized clinical trials with Haemaccel and various antiallergic drugs.

Even years after having sustained multiple injuries patients often suffer from its sequelae. These comprise restrictions in physical function, but also pain, social and psychological impairments. Although the Meran Consensus Conference in 1990 defined the contents of "quality of life" (QoL) measures in surgery, still no instrument is available for the valid assessment of all relevant QoL domains in multiple injured patients. This paper describes the systematic development of a modular instrument for the assessment of health related QoL. Within three phases (phase I: generation of items, phase II: item reduction, phase III: pre-testing in 70 multiple injured and control patients) a questionnaire of 57 items was developed, which measures all relevant trauma-related aspects of QoL after acute hospital care. In combination with the Glascow Outcome Scale (GOS), the EUROQOL and the SF-36, the newly developed instrument builds the Polytrauma Outcome Chart (POLO-Chart) which will also be used as "Part E" for outcome assessment within the "Trauma registry" of the German Society for Trauma Surgery. In phase IV, the POLO-Chart will finally be validated in five trauma centres (Celle, Essen, Hanover, Cologne und Munich).

[Systematic development of a scale for determination of health-related quality of life in multiple trauma patients. The Polytrauma Outcome (POLO) Chart].

E. Neugebauer

Papers

Definition and Classification of the Histamine-Release Response to Drugs in Anaesthesia and Surgery: Studies in the Conscious Human Subject* **

Das Traumaregister der Deutschen Gesellschaft für Unfallchirurgie

[Predicting the outcome in severe injuries: an analysis of 2069 patients from the trauma register of the German Society of Traumatology (DGU)].

H1 + H2-receptor antagonists for premedication in anaesthesia and surgery: a critical view based on randomized clinical trials with Haemaccel and various antiallergic drugs.

[Systematic development of a scale for determination of health-related quality of life in multiple trauma patients. The Polytrauma Outcome (POLO) Chart].