Non-surgical external jugular vein catheterization using an ear vein access in piglets.

The objective of this study was to investigate the feasibility of external jugular vein catheterization through an ear vein in piglets. Forty-six sevoflurane-midazolam anaesthetized piglets were included. External jugular vein catheterization was conducted through the ear vein using the Seldinger technique. Part 1 (n = 27): optimal puncture site was based on the deltoid tuberosity as a landmark to reach the external jugular vein. The final position of the catheter was verified in 25 piglets using computer tomography. Catheterization time was recorded and patency of the catheter assessed by repeated blood sampling for up to 4 h. Part 2 (n = 19): ear vein catheterization was without taking into account any landmarks. Functionality for blood sampling was evaluated as described in part 1. Catheter advancement was possible in 25/27 and 18/19 piglets in parts 1 and 2, respectively. Median (range) time required for successful catheterization was 1.95 (1-10) min (n = 38). The deltoid tuberosity was a good landmark to reach the external jugular vein. But blood sampling was also possible through catheters ending slightly cranial to the external jugular vein. Despite successful catheter advancement, blood sampling was not possible from one catheter in each part of the study (total: two piglets). One of these catheters presented luminal damage, while the other one presented as normal after being removed from the animal. Summarizing, central vein catheterization through the ear vein was feasible in 93.5% and repeated blood sampling was possible in 89.1% of the piglets (n = 46).

Effects of moderate and severe arterial hypotension on intracerebral perfusion and brain tissue oxygenation in piglets.

BACKGROUND: Hypotension is common in anaesthetised children, and its impact on cerebral oxygenation is unknown. The goal of the present study was to investigate the effects of moderate systemic arterial hypotension (mHT) and severe hypotension (sHT) on cerebral perfusion and brain tissue oxygenation in piglets. METHODS: Twenty-seven anaesthetised piglets were randomly allocated to a control group, mHT group, or sHT group. Cerebral monitoring comprised a tissue oxygen partial pressure ( [Formula: see text] ) and laser Doppler (LD) perfusion probe advanced into the brain tissue, and a near-infrared spectroscopy sensor placed over the skin measuring regional oxygen saturation (rSO2). Arterial hypotension was induced by blood withdrawal and i.v. nitroprusside infusion [target MAP: 35-38 (mHT) and 27-30 (sHT) mm Hg]. Data were analysed at baseline, and every 20 min during and after treatment. RESULTS: Compared with control, [Formula: see text] decreased equally with mHT and sHT [mean (SD) after 60 min: control: 17.1 (6.4); mHT: 6.4 (3.6); sHT: 7.2 (4.3) mm Hg]. No differences between groups were detected for rSO2 and LD during treatment. However, in the sHT group, rSO2 increased after restoring normotension [from 49.3 (9.5) to 58.9 (8.9)% Post60]. sHT was associated with an increase in blood lactate [from 1.5 (0.4) to 2.4 (0.9) mmol L-1], and a decrease in bicarbonate [28 (2.4) to 25.8 (2.6) mmol L-1] and base excess [4.7 (1.9) to 2.0 (2.7) mmol L-1] between baseline and 60 min after the start of the experiment. CONCLUSIONS: Induction of mHT and sHT by hypovolaemia and nitroprusside infusion caused alterations in brain tissue oxygenation in a piglet model, but without detectable changes in brain tissue perfusion and regional oxygen saturation.

Intraoperative music application in children and adolescents - a pilot study.

BACKGROUND: Hospitalization, surgery and anaesthesia may lead to new-onset maladaptive behaviour, emotional distress and trauma. This pilot study aims to investigate the influence of intraoperatively applied music on post-operative behaviour in children and adolescents. METHODS: Children with an ASA physical state classification of I or II, aged from 4 to 16 years and scheduled for elective circumcision or inguinal hernia repair under combined general and caudal anaesthesia were included. The children were randomized into two groups. They wore headphones during surgery, and were either exposed to music or not. All involved staff were blinded. Post-operative behaviour was documented by parents on day 7, 14 and 28 after surgery, using a questionnaire adapted from the "Post Hospitalization Behavioural Questionnaire" (PHBQ). Overall occurrence of at least one item indicating maladaptive behaviour was the primary outcome. Data are presented as median (interquartile range). RESULTS: In total, 135 children aged 6.6 (5.3-8.5) years, weighing 22 (19-29) kg, were included, with 112 completed questionnaires returned. Overall occurrence of at least one maladaptive item was lower in the music group, with a significantly lower incidence on day 7 (51% vs. 77% in controls; P < 0.01). CONCLUSION: Intraoperative music application in children undergoing minor surgical procedures may reduce the incidence of post-operative maladaptive behaviour within the first week.

Fentanyl bolus induces muscle tremors in sevoflurane-anaesthetized piglets.

Intravenous fentanyl (10 mcg/kg) or saline (control) was randomly administered to 10 healthy sevoflurane-mono-anaesthetized piglets. Trembling was assessed by two blinded observers using a visual analogue scale (VAS) and a simple ordinal scale at baseline and 5 min (T5) after drug administration. If no trembling was observed at that time point, the opposite treatment was administered and piglets were re-evaluated after another 5 min (T10). Four out of five piglets showed trembling after fentanyl (T5), while none given saline showed any trembling. With fentanyl the VAS scores were significantly higher at T5 compared either with baseline or with the control treatment. Control animals received fentanyl after the 5 min evaluation and all piglets showed clear trembling afterwards. The median time after fentanyl administration until first muscle tremors was 51 (20-840) s. In summary, nine out of 10 sevoflurane-anaesthetized piglets showed muscle tremors after intravenous fentanyl. Tremors subsided over time and no specific treatment was necessary.

Higher fibrinogen concentrations for reduction of transfusion requirements during major paediatric surgery: A prospective randomised controlled trial.

BACKGROUND: Hypofibrinogenaemia is one of the main reasons for development of perioperative coagulopathy during major paediatric surgery. The aim of this study was to assess whether prophylactic maintenance of higher fibrinogen concentrations through administration of fibrinogen concentrate would decrease the volume of transfused red blood cell (RBCs). METHODS: In this prospective, randomised, clinical trial, patients aged 6 months to 17 yr undergoing craniosynostosis and scoliosis surgery received fibrinogen concentrate (30 mg kg(-1)) at two predefined intraoperative fibrinogen concentrations [ROTEM(®) FIBTEM maximum clot firmness (MCF) of <8 mm (conventional) or <13 mm (early substitution)]. Total volume of transfused RBCs was recorded over 24 h after start of surgery. RESULTS: Thirty children who underwent craniosynostosis surgery and 19 children who underwent scoliosis surgery were treated per protocol. During craniosynostosis surgery, children in the early substitution group received significantly less RBCs (median, 28 ml kg(-1); IQR, 21 to 50 ml kg(-1)) compared with the conventional fibrinogen trigger of <8 mm (median, 56 ml kg(-1); IQR, 28 to 62 ml kg(-1)) (P=0.03). Calculated blood loss as per cent of estimated total blood volume decreased from a median of 160% (IQR, 110-190%) to a median of 90% (IQR, 78-110%) (P=0.017). No significant changes were observed in the scoliosis surgery population. No bleeding events requiring surgical intervention, postoperative transfusions of RBCs, or treatment-related adverse events were observed. CONCLUSIONS: Intraoperative administration of fibrinogen concentrate using a FIBTEM MCF trigger level of <13 mm can be successfully used to significantly decrease bleeding, and transfusion requirements in the setting of craniosynostosis surgery, but not scoliosis. CLINICAL TRIAL REGISTRY NUMBER: ClinicalTrials.gov NCT01487837.

Electrocardiographic and haemodynamic alterations caused by three different test solutions of local anaesthetics to detect accidental intravascular injection in children.

BACKGROUND: The aim of this study was to investigate ECG and haemodynamic alterations provoked by a test dose of bupivacaine, epinephrine, and their combination. METHODS: Paediatric patients undergoing general anaesthesia were randomized into three groups. After anaesthesia induction and tracheal intubation, 0.2 ml kg(-1) (max. 3 ml) of the corresponding test solution was i.v. injected: bupivacaine 0.125% (Group B), bupivacaine 0.125% plus epinephrine 1:200 000 (Group BE), or epinephrine 1:200 000 (Group E). ECG was printed and analysed post hoc. Non-invasive arterial pressure (AP) was measured at 1 and 2 min after test dose injection. Increases in T-wave of ≥ 25%, in heart rate (HR) of ≥ 10 beats min(-1), and in systolic AP of ≥ 15 mm Hg above baseline value were considered a positive result. RESULTS: A total of 105 children aged 0.2-16 (median 6.8) yr were enrolled. Test dose injection provoked T-wave elevation in 0%, 85%, and 89% of patients in Groups B, BE, and E, respectively. A positive increase in HR was found in 0%, 68%, and 76%. A positive increase in AP at 1 min was found in 0%, 88%, and 94% and at 2 min in 0%, 42%, and 59%. A decrease in HR of ≥ 10 beats min(-1) was observed in 6%, 76%, and 69%. Alterations in T-wave and HR were significantly influenced by age. CONCLUSIONS: ECG and haemodynamic alterations after i.v. injection of a local anaesthetic test dose were significantly influenced by epinephrine. T-wave elevation, increase in AP, and changes in HR are highly reliable variables, particularly when age is taken into account.

Comparison of air-sealing characteristics of tapered- vs. cylindrical-shaped high-volume, low-pressure tube cuffs.

BACKGROUND: This study aimed at comparing air-sealing characteristics of the new tapered-shaped tracheal tube cuffs with cylindrical tube cuffs. METHODS: Tracheal tubes with tapered-shaped polyurethane (PU) and polyvinyl chloride (PVC) cuffs as well as standard cylindrical-shaped cuffs made of PU and PVC (Covidien, Athlone, Ireland) were investigated. A tracheal model attached to a test lung was intubated, and cuffs were inflated to 10, 15, 20, 25 and 30 cm H(2)O. The test lung was ventilated with intermittent positive pressure ventilation at peak inspiratory pressures (PIPs) of 20 and 25 cm H(2)O. Air leakage was assessed by spirometry and measurement of sevoflurane concentration passing the cuff at the upper cuff border using an anaesthetic gas analyser. Experiments were repeated four times with new tracheal tubes for each run. Statistical comparisons were done using Mann-Whitney U-test with level of significance at P < 0.05. RESULTS: The tapered-shaped PVC tube cuff demonstrated a significantly lower air leakage determined by spirometry than the cylindrical-shaped cuff at both PIPs (20 and 25 cm H(2)O). Similarly, sevoflurane leakage was less with the tapered PVC cuff particularly at higher cuff pressures. With the PU cuff, reduction in air leakage by a tapered-shaped compared with a cylindrical-shaped tube cuff was not significant. CONCLUSIONS: A tapered-shaped tube cuff considerably improves air-sealing characteristics of PVC tube cuffs and allows thereby reducing cuff pressure required for sufficient ventilation. In tube cuffs made of PU that exhibits superior sealing characteristics compared with PVC, a tapered shape failed to result in a further reduction of air leakage.

Comparison of thromboelastometry (ROTEM®) with standard plasmatic coagulation testing in paediatric surgery.

BACKGROUND: Thromboelastometry (ROTEM(®)) might be useful to detect intraoperative coagulation disorders early in major paediatric surgery. This observational trial compares this technique to standard coagulation tests. METHODS: Intraoperative blood sampling was obtained in children undergoing elective major surgery. At each time point, standard coagulation tests [activated partial thromboplastin time (aPTT), prothrombin time (PT), and fibrinogen level] and ROTEM(®) analyses (InTEM, ExTEM, and FibTEM) were performed simultaneously by trained hospital laboratory staff. RESULTS: A total of 288 blood samples from 50 subjects were analysed. While there was a poor correlation between PT and aPTT to ExTEM clotting time (CT) and InTEM CT, respectively, a good correlation was detected between PT and aPTT to clot formation time, and a very good correlation between fibrinogen level and FibTEM assay (r=0.882, P<0.001). Notably, 64% of PT and 94% of aPTT measurements were outside the reference range, while impaired CT was observed in 13% and 6.3%, respectively. Standard coagulation test results were available after a median of 53 min [inter-quartile range (IQR): 45-63 min], whereas 10 min values of ROTEM(®) results were available online after 23 min (IQR: 21-24 min). CONCLUSIONS: PT and aPTT cannot be interchangeably used with ROTEM(®) CT. Based on the results of ROTEM(®), recommended thresholds for PT and aPTT might overestimate the need for coagulation therapy. A good correlation was found between the fibrinogen level and the FibTEM assay. In addition, ROTEM(®) offered faster turnaround times.

Accuracy and precision of hemoglobin point-of-care testing during major pediatric surgery.

INTRODUCTION: The aim of the study was to compare accuracy and reproducibility of four point-of-care testing (POCT) devices (GEM® Premier 3000, ABL 800 flex, GEM® OPL™, HemoCue® B-Hemoglobin) for hemoglobin (Hb) analyzes as compared with the reference laboratory method (Sysmex XE 2100) in children undergoing major surgery. METHODS: Pediatric patients undergoing craniofacial, spine, hip, or cancer surgery were included. Blood samples for Hb testing were taken at several intraoperative time points and generally withdrawn from the arterial catheter, if accessible. RESULTS: A total of 256 blood samples were taken intraoperatively from 71 pediatric patients. All POCT devices showed very small bias (maximum -0.46 g/dL) to reference method as well as very good reproducibility (maximum coefficient of variation of 0.99%). However, in two cases (HemoCue), potential clinical relevant differences were observed beyond a range of 2 g/dL. CONCLUSION: All POCT devices tested and operated by trained staff for hemoglobinometry showed reliable test results. They all allow for simple, fast, and precise bedside determination of hemoglobin concentration in the intraoperative setting.

[Bupivacaine toxicity and propofol anesthesia : animal study on intravascular bupivacaine injection]. / Bupivacaintoxizität und Propofolanästhesie : Tierstudie zur intravasalen Bupivacaininjektion.

BACKGROUND: Several reports have confirmed the efficacy of Intralipid® (containing soya bean oil, egg phospholipids, glycerin and water) in the therapy of systemic local anesthetic intoxication. Pretreatment with Intralipid® shifted the dose-response to bupivacaine-induced asystole in rats. Whether intravenous anesthesia with propofol in the widely used medium chain triglyceride lipid emulsion increases the therapeutic range of systemically administered bupivacaine or not is unknown and was investigated in this study. METHODS: A total of 30 piglets aged 2-6 weeks and weighing 4.5-6.5 kg were randomized into 2 groups and anesthetized with sevoflurane (group S) alone or with propofol 10 mg/kg body weight (BW)/h plus sevoflurane (group PS). After 60 min of steady state anesthesia arterial blood was sampled for assessment of blood gases, acid-base state and triglyceride plasma concentrations. Thereafter bupivacaine 0.125% was continuously infused by an infusion syringe pump through a central venous line at a rate of 4 mg/kg BW/min until invasively measured mean arterial pressure (MAP) was reduced by 50% of initial value. The bupivacaine infusion was stopped, blood for assessment of bupivacaine plasma concentration was drawn and the spontaneous hemodynamic course was observed. Resuscitation was not attempted. Results are presented as median and range. The Mann-Whitney U-test was used to assess differences between the two groups for triglyceride as well as for bupivacaine plasma concentrations measured at MAP 50%. A p-value≤0.05 was considered to be significant. RESULTS: Baseline conditions (arterial blood pH, plasma protein and triglyceride plasma concentrations) did not differ significantly between the two groups. After 1 h of anesthesia, triglyceride plasma concentrations were significantly increased in group PS (median 0.69 mmol/l) compared to the corresponding baseline values (median 0.14 mmol/l; p<0.001) and to the 1 h values of group S (median 0.16 mmol/l; p<0.001). The total amount of bupivacaine administered was 9 mg/kg BW in both groups (6-13 mg/kg BW in group S, 5-13 mg/kg BW in group PS). Resulting bupivacaine plasma concentrations were 180 µmol/l (83-686 µmol/l) in group S and 185 µmol/l (130-465 µmol/l) in group PS. However, the total amount of bupivacaine administered and bupivacaine plasma concentrations at MAP 50% did not reveal statistically significant differences between the two groups but a huge variability of both parameters within each group was observed. None of the 30 piglets spontaneously recovered and they died from pulseless electrical activity or from asystolic cardiac arrest. The time from MAP 50% until cardiac arrest demonstrated a large variability but did not reveal significant differences between the two groups. The time to cardiac arrest was similar in both groups. CONCLUSION: Medium/long chain triglyceride lipid emulsion (50:50) as widely used in propofol solutions did not increase therapeutic safety in cases of intravascular bupivacaine administration in this piglet model.

Saliva: diagnostics and therapeutic perspectives.

For the past two decades, salivary diagnostic approaches have been developed to monitor oral diseases such as periodontal diseases and to assess caries risk. Recently, the combination of emerging biotechnologies and salivary diagnostics has extended the range of saliva-based diagnostics from the oral cavity to the whole physiologic system as most compounds found in blood are also present in saliva. Accordingly, saliva can reflect the physiologic state of the body, including emotional, endocrinal, nutritional and metabolic variations and acts as a source for the monitoring of oral and also systemic health. This review presents an update on the status of saliva diagnostics and delves into their applications to the discovery of biomarkers for cancer detection and therapeutic applications. Translating scientific findings of nucleic acids, proteins and metabolites in body fluids to clinical applications is a cumbersome and challenging journey. Our research group is pursuing the biology of salivary analytes and the development of technologies for detection of distinct biomarkers with high sensitivity and specificity. The avenue of saliva diagnostics incorporating transcriptomic, proteomic and metabolomic findings will enable us to connect salivary molecular analytes to monitor therapies, therapeutic outcomes, and finally disease progression in cancer.

Electrocardiographic changes during continuous intravenous application of bupivacaine in neonatal pigs.

BACKGROUND: It is controversial as to whether T-wave elevation is caused by local anaesthetics, epinephrine, or their combination. It has been shown that T-elevation after intravascular injection of a small bupivacaine test dose is caused by epinephrine and not by bupivacaine. The aim of this study was to investigate ECG changes with higher doses of i.v. bupivacaine. METHODS: Thirty neonatal pigs were anaesthetized with sevoflurane and their tracheas intubated and artificially ventilated. Under steady-state conditions, bupivacaine was continuously infused (flow rate 3.2 ml kg(-1) min(-1)) by a syringe infusion pump through a central venous catheter. Group 1 received bupivacaine 0.125%, Group 2 bupivacaine 0.5%. The ECG was continuously printed and subsequently analysed for alterations in heart rate, ventricular de- and repolarization, and arrhythmias at 1.25, 2.5, and 5 mg kg(-1) bupivacaine infused. RESULTS: Sinus rhythm persisted in all pigs. Heart rate decreased progressively in both groups, but this was significantly more pronounced in Group 1. T-wave elevation occurred in 40% and 0% (Groups 1 and 2) at 1.25 mg kg(-1), in 80% and 0% at 2.5 mg kg(-1), and in 93% and 80% at 5 mg kg(-1) bupivacaine infused. There were significant differences between the two groups at 1.25 and 2.5 mg kg(-1) infused. CONCLUSIONS: Higher doses of i.v. infused bupivacaine can cause T-elevation. With slower injection technique, T-elevation can already be detected at lower bupivacaine doses administered.

Effect of tracheal tube cuff shape on fluid leakage across the cuff: an in vitro study.

BACKGROUND: This study compared the fluid leakage in the new 'tapered' shaped against the classic 'cylindrical' shaped tracheal tube cuffs when placed in different sized tracheas. METHODS: The 7.5 mm internal diameter (ID) tracheal tube cuffs-Tapered Seal Guard (TSG), Standard Seal Guard (SSG), Hi-Lo, Microcuff, Ruesch, and Portex Profile-were compared in an in vitro apparatus. Vertical artificial tracheas with 16, 20, and 22 mm ID were intubated, 5 ml clear water was applied above the unlubricated tube cuffs, and fluid leakage was measured up to 60 min. Data of tapered vs non-tapered tube cuffs (16 observations) were compared for each tracheal diameter using the Mann-Whitney test. RESULTS: Median (range) fluid leakage (ml) at 60 min was 2.14 (0.05-4.88), 1.14 (0.00-4.84), and 0.13 (0.00-1.32), respectively, for 16, 20, and 22 mm tracheas in the TSG tube studies when compared with 4.58 (0.44-4.88), 2.21 (0.00-4.81), and 0.00 (0.00-4.81) in the SSG tube and 4.54 (1.54-4.82), 0.90 (0.00-4.49), and 4.85 (4.40-4.99) in the Microcuff tube studies. Leakage in all polyvinylchloride (PVC) tube cuffs was almost complete (5 ml) within 5 min (P<0.001). CONCLUSIONS: The tapered PU tube cuff was as effective as the cylindrical PU cuffs in smaller tracheal diameters and was more efficient than the cylindrical Microcuff PU tube cuff in larger tracheal diameter in preventing subglottic fluid leakage across the tube cuff tested in this in vitro study. PVC tube cuffs leaked much more and faster than PU cuffs.

Cathepsin S genotypes are associated with Apo-A1 and HDL-cholesterol in lean and obese French populations.

Cathepsin S (CTSS) is a cysteine protease that has a central role in remodeling the extracellular matrix and, as such, has been implicated in the etiology of cardiovascular disease. This study used five tag single nucleotide polymorphisms (tSNPs) to screen the CTSS gene in healthy lean (n = 1891) and obese French populations (n = 477) for their association with various phenotypes: body mass index, waist-to-hip ratio, glycemia, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo-A1) and apolipoprotein B. Significant associations were identified between rs11576175 tSNP (A/G) and Apo-A1 and HDL-C plasma levels in a sex-specific manner. Lean female subjects homozygous for the minor A-allele had higher levels of circulating Apo-A1 (p = 0.0003), while lean male A/A carriers had higher levels of HDL-C (p = 0.007) compared with the other genotypes. In the obese cohort, associations were found between three tSNPs and Apo-A1 levels in adult female subjects: rs10888390 (G/A), p = 0.01; rs10888394 (T/C), p = 0.03; and rs1136774 (C/T), p = 0.02; however, only rs10888390 remained significant in a combined model (p = 0.03). These results provide the first evidence that CTSS sequence variations are associated with two human metabolic risk factors for cardiovascular diseases: plasma Apo-A1 and HDL-C concentrations.

Contribution of adenosine receptors in the control of arteriolar tone and adenosine-angiotensin II interaction.

Adenosine (Ado) mediates vasoconstriction via A(1)-Ado receptors and vasodilation via A(2)-Ado receptors in the kidney. It interacts with angiotensin II (Ang II), which is important for renal hemodynamics and tubuloglomerular feedback (TGF). The aim was to investigate the function of Ado receptors in the Ado-Ang II interaction in mouse microperfused, afferent arterioles. Ado (10(-11)-10(-4) mol/l) caused a biphasic response: arteriolar diameters were reduced (-7%) at Ado 10(-11)-10(-9) mol/l and returned to control values at higher concentrations. Treatment with Ang II (10(-10) mol/l) transformed the response into a concentration-dependent constriction. N(6)-cyclopentyladenosine (A(1)-Ado receptor agonist) reduced diameters (12% at 10(-6) mol/l). Application of CGS21680 (10(-12)-10(-4) mol/l, A(2A) receptor agonist) increased the diameter by 13%. Pretreatment with ZM241385 (A(2A)-Ado receptor antagonist) alone or in combination with MRS1706 (A(2B)-Ado receptor antagonist) resulted in a pure constriction upon Ado, whereas 8-cyclopentyltheophylline (CPT) (A(1)-Ado receptor antagonist) inhibited the constrictor response. Afferent arterioles of mice lacking A(1)-Ado receptor did not show constriction upon Ado. Treatment with Ado (10(-8) mol/l) increased the response upon Ang II, which was blocked by CPT. Ado (10(-5) mol/l) did not influence the Ang II response, but an additional blockade of A(2)-Ado receptors enhanced it. The action of Ado on constrictor A(1)-Ado receptors and dilatory A(2)-Ado receptors modulates the interaction with Ang II. Both directions of Ado-Ang II interaction, which predominantly leads to an amplification of the contractile response, are important for the operation of the TGF.