The impact of acquired coagulation factor XIII deficiency in traumatic bleeding and wound healing.

Factor XIII (FXIII) is a protein involved in blood clot stabilisation which also plays an important role in processes including trauma, wound healing, tissue repair, pregnancy, and even bone metabolism. Following surgery, low FXIII levels have been observed in patients with peri-operative blood loss and FXIII administration in those patients was associated with reduced blood transfusions. Furthermore, in patients with low FXIII levels, FXIII supplementation reduced the incidence of post-operative complications including disturbed wound healing. Increasing awareness of potentially low FXIII levels in specific patient populations could help identify patients with acquired FXIII deficiency; although opinions and protocols vary, a cut-off for FXIII activity of ~ 60-70% may be appropriate to diagnose acquired FXIII deficiency and guide supplementation. This narrative review discusses altered FXIII levels in trauma, surgery and wound healing, diagnostic approaches to detect FXIII deficiency and clinical guidance for the treatment of acquired FXIII deficiency.

Warning criteria for MEP monitoring during carotid endarterectomy: a retrospective study of 571 patients.

Monitoring of transcranial electrical motor evoked potentials (tcMEP) during carotid endarterectomy (CEA) has been shown to effectively detect intraoperative cerebral ischemia. The unique purpose of this study was to evaluate changes of MEP amplitude (AMP), area under the curve (AUC) and signal morphology (MOR) as additional MEP warning criteria for clamping-associated ischemia during CEA. Therefore, the primary outcome was the number of MEP alerts (AMP, AUC and MOR) in the patients without postoperative motor deficit (false positives). We retrospectively reviewed data from 571 patients who received CEA under general anesthesia. Monitoring of somatosensory evoked potentials (SSEP) and tcMEP was performed in all cases (all-or-none MEP warning criteria). The percentages of false positives (primary parameter) of AMP, AUC and MOR were evaluated according to the postoperative motor outcome. In the cohort of 562 patients, we found significant SSEP/MEP changes in 56 patients (9.96%). In 44 cases (7.83%) a shunt was inserted. Nine patients (1.57%) were excluded due to MEP recording failure. False positives were registered for AMP, AUC and MOR changes in 121 (24.01%), 148 (29.36%) and 165 (32.74%) patients, respectively. In combination of AMP/AUC and AMP/AUC/MOR false positives were found in 9.52% and 9.33% of the patients. This study is the first to evaluate the correctness of the MEP warning criteria AMP, AUC and MOR with regard to false positive monitoring results in the context of CEA. All additional MEP warning criteria investigated produced an unacceptably high number of false positives and therefore may not be useful in carotid surgery for adequate detection of clamping-associated ischemia.

Intraoperative multimodal evoked potential monitoring during carotid endarterectomy: a retrospective study of 264 patients.

BACKGROUND: Methods for detecting intraoperative cerebral ischemia arising from internal carotid artery (ICA) cross-clamping during carotid endarterectomy (CEA) should be sensitive, specific, and rapid to prevent intraoperative stroke. We had 3 objectives pertaining to this: (1) investigation of the rates of success of multimodal evoked potential (mEP) monitoring using a combination of median nerve (m) somatosensory (SS) EPs, tibial nerve SSEPs (tSSEPs), and transcranial electrical stimulated motor EPs (tcMEPs); (2) evaluation of the rates of false-negative mEP results; and (3) analysis of the relationship between different time periods associated with ICA cross-clamping and the postoperative outcome of motor function in patients with significant changes in mEP monitoring. METHODS: Two hundred sixty-four patients undergoing CEA using general anesthesia with monitoring of bilateral mSSEPs, tSSEPs, and tcMEPs were retrospectively reviewed between 2009 and 2012. The rates of successful assessment of mEPs were investigated, and the rate of false-negative mEP results was analyzed. Different time periods (T1--time of clamping, T2--clamping to significant mEP changes, T3--significant mEP change to intervention, and T4--intervention to recovery of EP) were tested using Welch t test for significant association with postoperative motor deficit. RESULTS: (1) Multimodal EP monitoring was achieved in 241 patients (91.3%, point estimate [PE] 0.91, confidence interval [CI] 0.87 to 0.94), whereas none of the modalities were recordable in one case (PE 0.0038, CI 0.0002 to 0.019). Additionally, tSSEP was not recordable in 21 patients (PE 0.08, CI 0.05 to 0.12), and we found one case of isolated failure of tcMEP recording (PE 0.0038, CI 0.0002 to 0.019). (2) False-negative mEP results were found in 1 patient (0.4%; PE 0.0038, CI 0.0002 to 0.019). Significant mEP changes occurred in 32 patients (12.1%), and thus, arterioarterial shunt was performed in 17 (6.4%) patients. Eleven patients (4.2%) showed transient and 1 showed permanent postoperative motor deficit. (3) There was no significant difference regarding any of the time periods associated with ICA cross-clamping and postoperative alteration of motor function (T1: P = 0.19, CI -30.1 to 6.8 minutes; T2: P = 0.38, CI -23 to 9.5 minutes; T3: P = 0.25, -9.7 to 2.8 minutes; T4: P = 0.42, CI to -15.5 to 7.0 minutes). CONCLUSIONS: Multimodal EP monitoring is applicable during CEA. The 0.4% false-negative rate suggests an advantage of mEP monitoring when compared with isolated mSSEP monitoring. Our data suggest that periods of time during cross-clamping were not significantly associated with postoperative motor deficit. However, the small number of patients limits the conclusiveness of these findings. mEP monitoring could not prevent a postoperative motor deficit in all patients, but our results suggest that it is a useful adjunct to mSSEP monitoring.

Comparison of Enk Fibreoptic Atomizer with translaryngeal injection for topical anaesthesia for awake fibreoptic intubation in patients at risk of secondary cervical injury: A randomised controlled trial.

BACKGROUND: Two methods of topical anaesthesia for awake fibreoptic intubation (FOI) in patients at risk of secondary cervical injury were compared: the translaryngeal injection (TLI) technique and the Enk Fibreoptic Atomizer. OBJECTIVE: The objective of this study was to determine which system of topical anaesthesia provides the fastest and most comfortable awake FOI, using the oral approach. DESIGN: A randomised controlled study. SETTING: A single centre trial between 2009 and 2011. PATIENTS: One hundred and twenty patients (63 women, 57 men) who underwent neurosurgery of the spine at Klinikum St. Georg Leipzig were randomly allocated into two groups (group TLI, 61 patients; group ENK-ATOMIZER, 59 patients). Inclusion criteria were an American Society of Anesthesiology (ASA) physical status of 1 to 3, age 18 to 80 years, and those who met any one of three indications for FOI - cervical instability, predicted difficult airway, a BMI greater than 40 kg m(-2), and who gave written informed consent.Exclusion criteria were emergency awake FOI, mental disability/delirium, polytrauma and contraindication to TLI. INTERVENTIONS: Two anaesthesiologists experienced in both techniques performed all anaesthesia procedures within the study. MAIN OUTCOME MEASURES: The primary outcome was the timing sequence of awake FOI. The incidence of coughing/gagging, ease of tracheal tube placement, mucosal bleeding, cardiopulmonary stability and postoperative outcomes were also investigated. RESULTS: Awake FOI was significantly faster using the TLI technique (mean, 191 s; range, 123 to 447 s; SD, 83.5) than the Enk Fibreoptic Atomizer [mean, 430 s; range, 275 to 773 s; SD, 124.9; (P = 0.0001)]. Patients in group TLI exhibited significantly less gagging (P = 0.047) but more mucosal bleeding (P <  .001). CONCLUSION: Awake FOI using the TLI technique was faster and provided better topical anaesthesia with less gagging during endoscopic intubation. However, the TLI technique was also more invasive. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00948350.

Antithrombin III, but not C1 esterase inhibitor reduces inflammatory response in lipopolysaccharide-stimulated human monocytes in an ex-vivo whole blood setting.

In order to examine the immunomodulatory effects of antithrombin III (AT-III) and C1 esterase inhibitor (C1-INH) in human monocytes, we investigated the intracellular expression of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α in an ex-vivo laboratory study in a whole blood setting. Heparinized whole blood samples from 23 healthy male and female volunteers (mean age: 27±7years) were pre-incubated with clinically relevant concentrations of AT-III (n=11) and C1-INH (n=12), then stimulated with 0.2 ng/mL lipopolysaccharide (LPS) for 3h. After phenotyping CD14⁺ monocytes, intracellular expression of IL-6, IL-8, and TNF-α was assessed using flow cytometry. In addition, 12 whole blood samples (AT-III and C1-INH, n=6 each) were examined using hirudin for anticoagulation; all samples were processed in the same way. To exclude cytotoxicity effects, 7-amino-actinomycin D and Nonidet P40 staining were used to investigate probes. This study is the first to demonstrate the influence of C1-INH and AT-III on the monocytic inflammatory response in a whole blood setting, which mimics the optimal physiological setting. Cells treated with AT-III exhibited significant downregulation of the proportion of gated CD14⁺ monocytes for IL-6 and IL-8, in a dose-dependent manner; downregulation for TNF-α did not reach statistical significance. There were no significant effects on mean fluorescence intensity (MFI). In contrast, C1-INH did not significantly reduce the proportion of gated CD14⁺ monocytes or the MFI regarding IL-6, TNF-α, and IL-8. When using hirudin for anticoagulation, no difference in the anti-inflammatory properties of AT-III and C1-INH in monocytes occurs. Taken together, in contrast to TNF-α, IL-6 and IL-8 were significantly downregulated in monocytes in an ex-vivo setting of human whole blood when treated with AT-III. This finding implicates monocytes as an important point of action regarding the anti-inflammatory properties of AT-III in sepsis. C1-INH was unable to attenuate the monocytic response, which supports the hypothesis that other cellular components in whole blood (e.g., neutrophils) might be responsible for the known effects of C1-INH in inflammation.

Comparison of Aintree and Fastrach techniques for low-skill fibreoptic intubation in patients at risk of secondary cervical injury: a randomised controlled trial.

BACKGROUND: We compared two methods of asleep fibreoptic intubation in patients at risk of secondary cervical injury: the Aintree Intubation Catheter via a classic laryngeal mask airway (cLMA) versus the Fastrach technique via the intubating laryngeal mask airway (iLMA). OBJECTIVE: To test which system has the highest rate of successful intubations in the clinical setting. DESIGN: A randomised controlled study. SETTING: Single-centre, between 2007 and 2010. PATIENTS: We randomly allocated 80 patients (30 women and 50 men) who underwent elective neurosurgery of the cervical spine to either group, placed in a neutral position and wearing a soft cervical collar. Entry criteria were ASA status 1 to 3, age 18 to 80 years and written informed consent. Exclusion criteria were patients with cervical instability, known or predicted difficult airway, BMI greater than 40  kg  m⁻² and symptomatic gastro-oesophageal reflux. INTERVENTIONS: Two anaesthetists who were experienced in both techniques performed all anaesthesia procedures within the study. There was a maximum of three attempts for performing each technique. MAIN OUTCOME MEASURES: The primary outcome was the rate of successful fibreoptic intubation in a neutral position. We also investigated the timing sequence for both techniques, the Brimacombe and Berry Bronchoscopy Score, and differences in technical aspects. RESULTS: All 40 patients in the Aintree group but only 31 patients in the Fastrach group were intubated successfully. Thus, fibreoptic intubation failed significantly less using the Aintree technique (P = 0.002). For secondary outcomes, the cLMA was faster (260 versus 289  s, P = 0.039) and easier (P = 0.036) to insert than the iLMA. The fibreoptic view of the glottis according to the Brimacombe and Berry Bronchoscopy Score was better (P = 0.016) and the tracheal tube was easier to insert (P = 0.010) in the Aintree group. CONCLUSION: Fibreoptic intubation using the Aintree system was more successful than the Fastrach technique in our population of patients in a neutral position wearing a soft cervical collar. The differences in the time to successful intubation between the two groups are unlikely to be clinically relevant.

High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition and nosocomial infections in the ICU: a randomized clinical trial.

IMPORTANCE: Enteral administration of immune-modulating nutrients (eg, glutamine, omega-3 fatty acids, selenium, and antioxidants) has been suggested to reduce infections and improve recovery from critical illness. However, controversy exists on the use of immune-modulating enteral nutrition, reflected by lack of consensus in guidelines. OBJECTIVE: To determine whether high-protein enteral nutrition enriched with immune-modulating nutrients (IMHP) reduces the incidence of infections compared with standard high-protein enteral nutrition (HP) in mechanically ventilated critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: The MetaPlus study, a randomized, double-blind, multicenter trial, was conducted from February 2010 through April 2012 including a 6-month follow-up period in 14 intensive care units (ICUs) in the Netherlands, Germany, France, and Belgium. A total of 301 adult patients who were expected to be ventilated for more than 72 hours and to require enteral nutrition for more than 72 hours were randomized to the IMHP (n = 152) or HP (n = 149) group and included in an intention-to-treat analysis, performed for the total population as well as predefined medical, surgical, and trauma subpopulations. INTERVENTIONS: High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days. MAIN OUTCOMES AND MEASURES: The primary outcome measure was incidence of new infections according to the Centers for Disease Control and Prevention (CDC) definitions. Secondary end points included mortality, Sequential Organ Failure Assessment (SOFA) scores, mechanical ventilation duration, ICU and hospital lengths of stay, and subtypes of infections according CDC definitions. RESULTS: There were no statistically significant differences in incidence of new infections between the groups: 53% (95% CI, 44%-61%) in the IMHP group vs 52% (95% CI, 44%-61%) in the HP group (P = .96). No statistically significant differences were observed in other end points, except for a higher 6-month mortality rate in the medical subgroup: 54% (95% CI, 40%-67%) in the IMHP group vs 35% (95% CI, 22%-49%) in the HP group (P = .04), with a hazard ratio of 1.57 (95% CI, 1.03-2.39; P = .04) for 6-month mortality adjusted for age and Acute Physiology and Chronic Health Evaluation II score comparing the groups. CONCLUSIONS AND RELEVANCE: Among adult patients breathing with the aid of mechanical ventilation in the ICU, IMHP compared with HP did not improve infectious complications or other clinical end points and may be harmful as suggested by increased adjusted mortality at 6 months. These findings do not support the use of IMHP nutrients in these patients. TRIAL REGISTRATION: trialregister.nl Identifier: NTR2181.

The predictive role of Interleukin 6 in burn patients with positive blood cultures.

Interleukin 6 (IL-6) is an established biomarker of inflammation with one of the earliest responses in sepsis. Serum levels can easily be measured within a few hours. The clinical significance of IL-6 in the early stage of sepsis in burned patients has not yet been confirmed. The purpose of our research was to investigate the predictive value of IL-6 for positive blood cultures in comparison to Procalcitonin (PCT), white blood cell (WBC) count, body temperature and the Sequential Organ Failure Assessment (SOFA) score in the presence of suspected sepsis in burn patients. In a retrospective study, we included all patients admitted to a regional burn centre in a 7-year period. Patients with a clinical suspicion of sepsis and complete laboratory tests underwent further analysis. Patients were categorized following culture results into either positive or negative bloodstream infection (BSI or non-BSI) groups. 39 of the 101 included patients had positive blood cultures (BSI). The serum IL-6 levels were significantly higher in the BSI group [1047 (339.9; 9000.5) vs. 198.5 (112.4; 702.5) ng/l; P = 0.001]. Receiver operating characteristic (ROC) curve analysis showed an AUC of 0.7 (59; 80.8%). The optimal IL-6 cut-off level was 312.8 ng/l (sensitivity 79.5%, specificity 56.5%). Other biomarkers (PCT, WBC), the maximum body temperature and increase of SOFA score were not different between the groups. IL-6 can be used to predict a positive blood culture even in the early stage of suspected sepsis in burned patients. In this context, other biomarkers (PCT, WBC) and body temperature are of limited clinical utility.

Evaluation of MR-proANP and copeptin for sepsis diagnosis after burn injury.

PURPOSE: The significance of the validated biomarkers of sepsis Mid-regional pro-atrial natriuretic peptide (MR-proANP) and copeptin have not been tested in a burn injury setting. MATERIALS AND METHODS: 42 consecutive patients were included in a prospective observational study. Daily blood specimens collected over the initial 20 days of treatment were quantitatively analysed by immunoluminometric sandwich assay (Kryptor, BRAHMS, Berlin, Germany) for MR-proANP, copeptin and procalcitonin (PCT). RESULTS: In patients with absence of sepsis, copeptin levels initially increased post-burn injury and thereafter rapidly declined. In contrast, MR-proANP was only slightly elevated within the first few days. MR-proANP [199.8 (115.6; 399.5) vs 160.1 (93.7; 280.6), P < .007] and PCT [1.12 (0.32; 2.22) vs 0.32 (0.16; 0.53), P < .001] levels were significantly higher on days of sepsis. Copeptin, however, showed no significant differences [20.7 (11.8; 42.2) vs 16.8 (11.0; 30.6), P = .11]. Both, MR-proANP and PCT level increases were noted upon the first day of sepsis. CONCLUSION: Burn injury itself maybe associated with copeptin and to a lesser degree MR-proANP level increases. Subsequent increases in MR-proANP may be considered diagnostic for sepsis but demonstrated no advantages over PCT. The role of copeptin remains inappropriate for diagnosing sepsis after burn injury (ClinicalTrials.gov number, NCT01055587).

[Consumption of antibiotics in a burns intensive care unit]. / Antibiotikaverbrauch auf einer Intensivstation für Schwerbrandverletzte.

INTRODUCTION: Burn-injured patients are at particularly high risk of infection; as such one would expect an increased requirement of antibiotics compared to other intensive care patients. There is no data in the literature investigating this hypothesis in Germany. The aim of this study was to determine the antibiotic consumption in severe burn patients and to compare this data with those from surgical intensive care units. PATIENTS AND METHODS: The retrospective study included 136 patients treated in the period from 2013 to 2016 due to a severe burn in the ICU intensive care unit of a regional burn centre. The use of antibiotics was recorded using the electronic medical record. The number of daily doses in Recommended Daily Dose (RDD) and Defined Daily Dose (DDD) based on patient days was calculated. RESULTS: Median [interquartile range] age and total burned surface area were 56.5y [43-75y] and 17 % [8,75; 31] with an ABSI 7 [6; 9]. Antibiotic therapy was given to 82 patients (60.3 %). Antibiotic consumption totaled 77.38 RDD/100 PT or 937.64 DDD/1000 PT. This result was marginally lower than for surgical intensive care units. The most frequently used antibiotics in the burn care setting were fluorquinolones (16.90 RDD/100 PT, 259.91 DDD/1000 PT), followed by carbapenems (12.76 RDD/100 PT, 128.44 DDD/1000 PT) and aminopenicillins/ BLI (11.54 RDD/100 PT, 115.39 DDD/1000 PT). Whilst, the most frequently detected pathogens were Staphylococcus aureus (54.4 %), Enterococcus faecalis (54.4 %), E. coli (37.5 %) and Pseudomonas aeruginosa (36.8 %). CONCLUSION: The total antibiotic consumption in severe burns was not increased compared to other surgical intensive care patients. With regard to individual substance classes, peculiarities can be identified reflecting the particular germ spectrum in this cohort.