Optimisation of the dosage of tranexamic acid in trauma patients with population pharmacokinetic analysis.

Tranexamic acid is used both pre-hospital and in-hospital as an antifibrinolytic drug to treat or prevent hyperfibrinolysis in trauma patients; dosing, however, remains empirical. We aimed to measure plasma levels of tranexamic acid in patients receiving pre-hospital anti-hyperfibrinolytic therapy and to build a population pharmacokinetic model to propose an optimised dosing regimen. Seventy-three trauma patients were enrolled and each received tranexamic acid 1 g intravenously pre-hospital. A blood sample was drawn after arrival in the emergency department, and we measured the plasma tranexamic acid concentration using liquid chromatography-mass spectrometry, and modelled the data using non-linear mixed effect modelling. Tranexamic acid was administered at a median (IQR [range]) time of 43 (30-55 [5-135]) min after trauma. Plasma tranexamic acid levels were determined on arrival at hospital, 57 (43-70 [20-148]) min after pre-hospital administration of the drug. The measured concentration was 28.7 (21.5-38.5 [8.7-89.0]) µg.ml-1 . Our subjects had sustained severe trauma; injury severity score 20 (16-29 [5-75]), including penetrating injury in 2.8% and isolated traumatic brain injury in 19.7%. The pharmacokinetics were ascribed a two-compartment open model with body-weight as the main covariate. As tranexamic acid concentrations may fall below therapeutic levels during initial hospital treatment, we propose additional dosing schemes to maintain a specific target blood concentration for as long as required. This is the first study to investigate plasma level and pharmacokinetics of tranexamic acid after pre-hospital administration in trauma patients. Our proposed dosing regimen could be used in subsequent clinical trials to better study efficacy and tolerance profiles with controlled blood concentrations.

Change of transfusion and treatment paradigm in major trauma patients.

Trauma promotes trauma-induced coagulopathy, which requires urgent treatment with fixed-ratio transfusions of red blood cells, fresh frozen plasma and platelet concentrates, or goal-directed administration of coagulation factors based on viscoelastic testing. This retrospective observational study compared two time periods before (2005-2007) and after (2012-2014) the implementation of changes in trauma management protocols which included: use of goal-directed coagulation management; admission of patients to designated trauma centres; whole-body computed tomography scanning on admission; damage control surgery; permissive hypotension; restrictive fluid resuscitation; and administration of tranexamic acid. The incidence of massive transfusion (≥ 10 units of red blood cells from emergency department arrival until intensive care unit admission) was compared with the predicted incidence according to the trauma associated severe haemorrhage score. All adult (≥ 16 years) trauma patients primarily admitted to the University Hospital Zürich with an injury severity score ≥ 16 were included. In 2005-2007, the observed and trauma associated severe haemorrhage score that predicted the incidence of massive transfusion were identical, whereas in 2012-2014 the observed incidence was less than half that predicted (3.7% vs. 7.5%). Compared to 2005-2007, the proportion of patients transfused with red blood cells and fresh frozen plasma was significantly lower in 2012-2014 in both the emergency department (43% vs. 17%; 31% vs. 6%, respectively), and after 24 h (53% vs. 27%; 37% vs. 16%, respectively). The use of tranexamic acid and coagulation factor XIII also increased significantly in the 2012-2014 time period. Implementation of a revised trauma management strategy, which included goal-directed coagulation management, was associated with a reduced incidence of massive transfusion and a reduction in the transfusion of red blood cells and fresh frozen plasma.

Analysis of Ocular Firework-Related Injuries and Common Eye Traumata: a 5-year Clinical Study.

Background A comparative study of eye injuries related to fireworks or acts of violence around New Year's Eve and the Swiss National Day on August 1st. The two groups were compared with respect to the overall numbers of eye accidents within the period of review. Patients and Methods Retrospective analysis of emergency consultations at the Department of Ophthalmology, University Hospital Zurich with eye accidents around the Swiss National Day on August 1st and New Year's Eve over the last 5 years. Two subgroups were formed: (1) Firework-related eye traumata, (2) Eye injuries due to acts of violence. The groups were analysed by age, gender, active participant or bystander, eye involved, severity of trauma (from clinical findings), surgical interventions, time of follow-up and visits, visual acuity and outcome. Results The study included 97 patients (100 eyes) with 74 male (76 %) and 23 female (24 %) victims. After filtering out 67 common traumata cases (all unilateral), 17 patients (18 eyes) with firework-related injuries and 13 patients (15 eyes) with damage due to an act of violence remained. Firework injuries accounted for 18 % of cases (65 % men); eye injuries caused by an act of violence accounted for 15 % of cases (92 % men). In the fireworks group, women were significantly older than men (mean age men 32 ± 14 years versus women 38 ± 16 years, p = 0.002). 65 % of cases were bystanders. The two subgroups contained 30 patients (33 eyes) with 22 left eyes (67 %, p < 0.001). The anterior segment was most frequently involved (79 %), significantly more often than the posterior part of the eye (p < 0.001). The posterior segment was injured more often in the fireworks group (28 %), than in the violence group (13 %). 87 % of the victims in the group of common traumata were mild trauma, 10 % moderate and 3 % severe. In the fireworks group the distribution was 53 % mild, 12 % moderate and 35 % severe, in the violence group 46 %, 23 % and 31 % respectively. Severe trauma cases occurred significantly more often around the New Year, with 36 % versus August 1st with 18 % (p = 0.0028). They are more often related to firework injuries than caused by violence (40 % versus 33 %). In summary, 7 victims (23 %) needed 8 interventions, with 3 having additional issues with their intraocular pressure. Full final visual acuity was noted in 88 %, which was alike in the two subgroups. On the contrary common traumata happened significantly more often around August 1st (66 %) than New Year (34 %; p < 0.001). Conclusions The number of injured eyes in the two subgroups of fireworks and violence was twice as high around New Year's Eve than around the Swiss National Day. If the two events were combined, eye injuries were caused by an act of violence in 45 % and by fireworks in 55 % of cases. Injuries from fireworks can be decreased by professional fireworks. Both types of accident can be decreased by public awareness.

Accuracy of calculated volatile agent consumption from fresh gas content.

BACKGROUND: Case-by-case assessment of volatile anesthetic (VA) consumption is necessary to perform agent sparing dosing measures and for billing purposes. The gold standard technique for this purpose is to measure the weight difference of the vaporizer that occurs during VA delivery. Because suitable equipment is rarely available and weighing the vaporizer is only possible in prospectively planned fashion, a calculation method from recorded fresh gas flow (FGF) and VA courses is a viable alternative. The objective was to evaluate the accuracy of VA calculation from fresh gas composition vs. the gold standard of weighing the vaporizer before and after anesthesia. METHODS: In this prospective laboratory investigation, we compared the formula-based calculations of VA consumption to the measured vaporizer weight differences before and after 10 sevoflurane and 10 desflurane anesthesia. We assessed the average difference and spread of values between the calculated and the measured values. RESULTS: The calculated sevoflurane consumption overestimated the measured values by 3.0 ± 2.9 ml (6.2%). The calculated desflurane consumption overestimated the measured values by 3.5 ± 6.7 ml (5.0%). All pairs of values from both agents were within ± 1.96 standard deviations. CONCLUSION: The calculated VA consumption for sevoflurane and desflurane are sufficiently accurate to estimate the economic impact of VA delivery during inhalational anesthesia. This method enables the assessment of VA consumption both ways: (1) retrospectively from sufficiently detailed and accurate anesthesia recordings, as well as (2) by using this method in a prospective setting.

Concluding results from the first phase of the Zurich Unexpected Difficult Airway course based on exercise of technical skills.

We analysed the results of the first phase of the Zurich Unexpected Difficult Airway course. Two hundred and twenty-eight staff members performed a total of 2712 standardised airway rescue procedures with four airway devices: SensaScope™, LMA Fastrach™, Laryngeal Tube and needle cricothyrodotomy. Four consecutive attempts were performed using each device. We analysed the success rate and the time needed for successful completion for each attempt and device. The success rates and mean (SD) completion times for all participants were 96.2% and 30.2 (15.3) s for the SensaScope, 88.1% and 40.4 (17.2) s for the LMA Fastrach, 99.0% and 12.1 (10.6) s for the Laryngeal Tube and 99.0% and 12.3 (6.1) s for needle cricothyroidotomy. The learning curves resulting from the four consecutive attempts with each device showed a clear pattern of improvement. This institutional airway training course represents a promising method to improve the capability of practitioners to cope with unexpected difficult airway situations.

Delayed two-step free wall rupture of the right and left ventricular wall after myocardial infarction.

We present a 68-year-old female who suffered extensive complications after severe myocardial infarction (MI) in the circumflex (CX) territory. At 24 hours after the initial event, the patient presented with a covered right ventricular free wall rupture (FWR) which was followed by a rupture of the left posterior wall ten days later. We report here on a rare case of delayed two-step biventricular FWR after severe MI in the CX territory.

Relative concentrations of haemostatic factors and cytokines in solvent/detergent-treated and fresh-frozen plasma.

BACKGROUND: Indications, efficacy, and safety of plasma products are highly debated. We compared the concentrations of haemostatic proteins and cytokines in solvent/detergent-treated plasma (SDP) and fresh-frozen plasma (FFP). METHODS: Concentrations of the following parameters were measured in 25 SDP and FFP samples: fibrinogen (FBG), factor (F) II, F V, F VII, F VIII, F IX, F X, F XIII, von Willebrand factor (vWF), D-Dimers, ADAMTS-13 protease, tumour necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, IL-8, and IL-10. RESULTS: Mean FBG concentrations in SDP and FFP were similar, but in FFP, the range was larger than in SDP (P<0.01). Mean F II, F VII, F VIII, F IX, and F XIII levels did not differ significantly. Higher concentrations of F V (P<0.01), F X (P<0.05), vWF (P<0.01), and ADAMTS-13 (P<0.01) were found in FFP. With the exception of F VIII and F IX, the range of concentrations for all of these factors was smaller (P<0.05) in SDP than in FFP. Concentrations of TNF-α, IL-8, and IL-10 (all P<0.01) were higher in FFP than in SDP, again with a higher variability and thus larger ranges (P<0.01). CONCLUSIONS: Coagulation factor content is similar for SDP and FFP, with notable exceptions of less F V, vWF, and ADAMTS-13 in SDP. Cytokine concentrations (TNFα, IL-8, and IL-10) were significantly higher in FFP. The clinical relevance of these findings needs to be established in outcome studies.