Modern Paediatric Emergency Department: Potential Improvements in Light of New Evidence.

The increasing attendance of paediatric emergency departments has become a serious health issue. To reduce an elevated burden of medical errors, inevitably caused by a high level of stress exerted on emergency physicians, we propose potential areas for improvement in regular paediatric emergency departments. In an effort to guarantee the demanded quality of care to all incoming patients, the workflow in paediatric emergency departments should be sufficiently optimised. The key component remains to implement one of the validated paediatric triage systems upon the patient's arrival at the emergency department and fast-tracking patients with a low level of risk according to the triage system. To ensure the patient's safety, emergency physicians should follow issued guidelines. Cognitive aids, such as well-designed checklists, posters or flow charts, generally improve physicians' adherence to guidelines and should be available in every paediatric emergency department. To sharpen diagnostic accuracy, the use of ultrasound in a paediatric emergency department, according to ultrasound protocols, should be targeted to answer specific clinical questions. Combining all mentioned improvements might reduce the number of errors linked to overcrowding. The review serves not only as a blueprint for modernising paediatric emergency departments but also as a bin of useful literature which can be suitable in the paediatric emergency field.

Sildenafil affects the human Kir2.1 and Kir2.2 channels at clinically relevant concentrations: Inhibition potentiated by low Ba2.

Sildenafil (Viagra), the first approved and widely used oral drug for the treatment of erectile dysfunction, was occasionally associated with life-threatening ventricular arrhythmias in patients. Since inward rectifier potassium current (I K1) may considerably contribute to this arrhythmogenesis, we investigated the effect of sildenafil on the human Kir2.1 and Kir2.2, the prevailing subunits forming the ventricular I K1 channels. Experiments were performed by the whole-cell patch clamp technique at 37°C using Chinese hamster ovary cells transiently expressing the human Kir2.1 and Kir2.2 channels. Changes of both the inward and outward current components (at -110 and -50 mV, respectively) were tested to be able to consider the physiological relevance of the sildenafil effect (changes at -110 and -50 mV did not significantly differ, results at -50 mV are listed below). A significant Kir2.1 inhibition was observed at all applied sildenafil concentrations (16.1% ± 3.7%, 20.0% ± 2.6%, and 15.0% ± 3.0% at 0.1, 1, and 10 µM, respectively). The inhibitory effect of 0.1 µM sildenafil was potentiated by the presence of a low concentration of Ba2+ (0.1 µM) which induced only a slight Kir2.1 inhibition by 5.95% ± 0.75% alone (the combined effect was 35.5% ± 3.4%). The subtherapeutic and therapeutic sildenafil concentrations (0.1 and 1 µM) caused a dual effect on Kir2.2 channels whereas a significant Kir2.2 activation was observed at the supratherapeutic sildenafil concentration (10 µM: 34.1% ± 5.6%). All effects were fully reversible. This is the first study demonstrating that sildenafil at clinically relevant concentrations inhibits both the inward and outward current components of the main human ventricular I K1 subunit Kir2.1. This inhibitory effect was significantly potentiated by a low concentration of environmental contaminant Ba2+ in agreement with recently reported data on rat ventricular I K1 which additionally showed a significant repolarization delay. Considering the similar subunit composition of the human and rat ventricular I K1 channels, the observed effects might contribute to sildenafil-associated arrhythmogenesis in clinical practice.

Fourth branchial cleft anomaly in a 7-month-old infant: A case report and literature review.

Fourth branchial cleft anomalies are rare head and neck congenital lesions seen in children. They present as a neck inflammatory mass and arise essentially on the left side of the neck. We report the case of a 7-month-old female with a mass of the neck associated with respiratory distress. The mass was diagnosed as an incomplete fourth branchial cleft fistula. Surgical revision of the neck abscess from an external approach and plasma coblation of the orifice in the pyriform fossa by an endoscopic approach were performed.

Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in a dual way.

Bronchodilator aminophylline may induce atrial or less often ventricular arrhythmias. The mechanism of this proarrhythmic side effect has not been fully explained. Modifications of inward rectifier potassium (Kir) currents including IK1 are known to play an important role in arrhythmogenesis; however, no data on the aminophylline effect on these currents have been published. Hence, we tested the effect of aminophylline (3-100 µM) on IK1 in enzymatically isolated rat ventricular myocytes using the whole-cell patch-clamp technique. A dual steady-state effect of aminophylline was observed; either inhibition or activation was apparent in individual cells during the application of aminophylline at a given concentration. The smaller the magnitude of the control IK1, the more likely the activation of the current by aminophylline and vice versa. The effect was reversible; the relative changes at -50 and -110 mV did not differ. Using IK1 channel population model, the dual effect was explained by the interaction of aminophylline with two different channel populations, the first one being inhibited and the second one being activated. Considering various fractions of these two channel populations in individual cells, varying effects observed in the measured cells could be simulated. We propose that the dual aminophylline effect may be related to the direct and indirect effect of the drug on various Kir2.x subunits forming the homo- and heterotetrameric IK1 channels in a single cell. The observed IK1 changes induced by clinically relevant concentrations of aminophylline might contribute to arrhythmogenesis related to the use of this bronchodilator in clinical medicine.

Nicotine replacement therapy in surgical patients.

BACKGROUND AND AIMS: The effect in smokers of nicotine withdrawal following surgery may contribute to the development of postoperative delirium. Nicotine is known to increase myocardial oxygen demand, coronary vasoconstriction, and may cause platelet activation leading to thrombosis. All of this can negatively impact postoperative recovery. The aim of this study was to determine whether nicotine replacement therapy can overweigh its negative effects, reduce the incidence of delirium, reduce the need for sedatives/analgesics, and/or shorten the duration of artificial pulmonary ventilation. METHODS: This prospective randomized single-blind study was performed in a 21-bed ICU. Fifty-two patients (26 intervention/ 26 control) met the inclusion criteria. Patients in the intervention group received a 21mg nicotine patch daily until discharged from the ICU (up to 7 days), patients in the control group received a placebo patch. The incidence of delirium was monitored with the CAM-ICU test. Sedatives/analgesics used in the ICU, and the duration of both artificial ventilation as well as total ICU stay were recorded for both groups. RESULTS: Nicotine replacement in smokers did not reduce the incidence of delirium in patients who had undergone surgery. Neither did it statistically significantly affect the length of hospitalization, sedation, analgesia, or vasopressors. CONCLUSION: This study did not confirm the effect of nicotine replacement therapy in reducing the incidence of delirium, it did not shorten the total duration of ICU stay or artificial ventilation and there was no reduced sedation requirement. We therefore saw no beneficial effect in patients receiving nicotine replacement therapy following elective surgery.

Nutritional support in the early stage of critical illness - focused on energy and protein intake.

The aim of this article is to emphasize the importance of taking into account the mechanism of host's response to insult when choosing a nutritional strategy in the early phase of a critical illness. At the same time, the article discusses the risks associated with early aggressive nutritional intervention for both energy and protein intake. Today, it seems that the most optimal choice of nutritional support during the first week of stay in the ICU is a gradual increase in both energy and protein intake. In numerical terms, this means a daily increase in energy dose of approximately 5 kcal/kg/day and a daily increase in protein dose of 0.2 g /kg/day. However, this only applies to patients admitted to the ICU with a normal body mass index, i.e. without malnutrition or without obesity. Both of these categories require special attention beyond the scope of this article.

Hypoxemia/hypoxia and new concepts of oxygen therapy in intensive care.

Oxygen is biologically vital element sustaining life. The tissue oxygen delivery is therefore precisely regulated. The degree of tissue oxygenation is estimated by measurement of oxygen blood level. The lack of oxygen on cellular and tissue level can lead to organ failure and life-threatening condition. Important adaptive processes are activated during the sublethal hypoxia with goal to preserve cellular and tissue functions. Inadequate effort to correct hypoxia can cause either disturbance of the adaptation or undesirable tissue hyperoxia. This fact is taken into account in two currently proposed concepts: (1) precise control of arterial oxemia and (2) permissive hypoxemia. Recent literature supports rather restrictive strategy of oxygen therapy in critical care.

Distribution of data in cellular electrophysiology: Is it always normal?

The distribution of data presented in many electrophysiological studies is presumed to be normal without any convincing evidence. To test this presumption, the cell membrane capacitance and magnitude of inward rectifier potassium currents were recorded by the whole-cell patch clamp technique in rat atrial myocytes. Statistical analysis of the data showed that these variables were not distributed normally. Instead, a positively skewed distribution appeared to be a better approximation of the real data distribution. Consequently, the arithmetic mean, used inappropriately in such data, may substantially overestimate the true mean value characterizing the central tendency of the data. Moreover, a large standard deviation describing the variance of positively skewed data allowed 95% confidence interval to include unrealistic negative values. We therefore conclude that the normality of the electrophysiological data should be tested in every experiment and, if rejected, the positively skewed data should be more accurately characterized by the median and interpercentile range or, if justified (namely in the case of log-normal and gamma data distribution), by the geometric mean and the geometric standard deviation.

[Antibiotics therapy in critically ill patients: the other side of the coin].

The aim of this mini-review is to draw attention to the risk aspects associated with antibiotic treatment in critically ill patients. These include antibiotic underdosing in the early phase of sepsis if treatment is governed by pharmacopoeia and unnecessarily long exposure to antibiotics if treatment is guided by traditional recommendations for the length of antibiotic administration. The need for discussing the loading dose of antibiotics and routine monitoring of serum antibiotic concentrations during treatment is stated. Antibiotic-induced mitochondrial dysfunction and oxidative stress are also discussed. Indeed, both of these mechanisms, otherwise effective in inhibiting the growth of tumor cells, may play an important role in the prolonged course of multiorgan failure if antibiotic treatment is too long.

Current density as routine parameter for description of ionic membrane current: is it always the best option?

The current density (J) is a parameter routinely used to characterize individual ionic membrane currents. Its evaluation is based on the presumption that the magnitude of whole-cell ionic membrane current (I) is directly proportional to the cell membrane capacitance (C), i.e. I positively and strongly correlates with C and the regression line describing I-C relation intersects the y-axis close to the origin of coordinates. We aimed to prove the presumption in several examples and find whether the conversion of I to J could be always beneficial. I-C relation was analysed in several potassium currents, measured in rat atrial myocytes (in inward rectifier currents, IK1, and both the constitutively active and acetylcholine-induced components of acetylcholine-sensitive current, IK(Ach)CONST and IK(Ach)ACH), and in rat ventricular myocytes (transient outward current Ito). I-C correlation was estimated by the Pearson coefficient (r). A coefficient (k) was newly suggested describing deviation of the regression intercept from zero in currents with considerable r value. Based on mathematical simulations, I was satisfactorily proportional to C when r ≥ 0.6 and k ≤ 0.2 which was fulfilled in IK1 and IK(Ach)ACH (r = 0.84, k = 0.20, and r = 0.61, k = 0.06, respectively). I-C correlation was significantly positive, but weak in IK(Ach)CONST (r = 0.42), and virtually missing in Ito (r = 0.04). The impaired I-C proportionality in IK(Ach)CONST and Ito likely reflects heterogeneity of the channel expression. We conclude that the conversion of I to J should be avoided when I-C proportionality is absent. Otherwise, serious misinterpretation of data may arise.

Presepsin in the diagnostics of sepsis.

Sepsis remains one of the most common causes of death worldwide. It is caused by a complex of inadequate host responses to infection. It is also often difficult to distinguish sepsis from a non-infectious cause of systemic inflammatory response syndrome. Early identification of an infectious origin may dramatically help to improve the outcome and reduce mortality. That is the main reason why clinicians need fast, reliable and specific biomarkers for recognition of sepsis. Presepsin (sCD-14ST) is one of promising biomarkers, the level of which increases in response to a microbial infection in the host. As a glycoprotein expressed in the membranes of monocytes and macrophages, CD14 (cluster of differentiation 14) serves especially as a co-receptor of the lipopolysaccharide-lipopolysaccharide binding protein complexes, and activates the inflammatory cascade. Consequently, during the inflammatory reaction, sCD14-ST, known as presepsin, is cleaved away from plasma. The objective of this article is to determine the diagnostic value of presepsin in the diagnostics of sepsis, assessing its severity, and monitoring the effectiveness of therapeutic interventions, and to establish the prognostic value of this biomarker.

Multi-parametric functional hemodynamic optimization improves postsurgical outcome after intermediate risk open gastrointestinal surgery: a randomized controlled trial.

BACKGROUND: Perioperative goal directed therapy (pGDT) using flow monitoring has been associated with improved outcomes. However, its protocols are often based on stroke volume only: as a target for fluid loading, inotropic support and vasopressors (via mathematical coupling of systemic vascular resistance). In this trial, we have tested the multi-parametric pGDT protocol based on esophageal Doppler variables (corrected flow time, peak velocity) in intermediate-to-high risk patients undergoing gastrointestinal surgery. METHODS: Intermediate-to-high risk patients undergoing gastrointestinal surgery were randomized to standard care (control) or multi-parametric pGDT (intervention). Postoperative complications and death rate as well as hospital length of stay were assessed as primary and secondary outcomes. RESULTS: Overall, 140 patients (intervention, N.=71, and control, N.=69) were included and randomized out of 197 eligible. Higher vasoactive/inotropic drug use and lower fluid balance were observed in the intervention group leading to favorable hemodynamic profile. The pGDT intervention was associated with improved primary outcome (28 days mortality and morbidity defined as occurrence of any defined complication) - 20 patients (28.2%) versus 32 (46.4%) in the control group (P=0.036); RR 0.61 (95% CI: 0.39-0.95), P=0.03. No differences in mortality and hospital length of stay were observed between groups. CONCLUSIONS: In this monocentric trial the multi-parametric pGDT protocol based on domain specific functional hemodynamic parameters was associated with lower rate of postoperative complications in intermediate-to-high risk patients undergoing scheduled gastrointestinal procedures.

Exogenous surfactant as a bridge to prolonged "total lung rest" in severely injured patient during extracorporeal membrane oxygenation.

We report a case of a 20-year-old male patient suffering from motorcycle accident complicated by rapid development of severe refractory hypoxemia and hypercapnia due to serious bilateral lung contusions and lacerations. Positive pressure mechanical ventilation induced pressure-dependent massive air leak from disrupted pulmonary tissue. Simultaneous implementation of veno-venous extracorporeal membrane oxygenation together with surfactant application allowed prolonged disconnection of patient from mechanical ventilation ("total lung rest" mode). Despite considerable areas of nonaerated tissue on computed tomography prior to the disconnection from mechanical ventilation, almost total functional recovery of lungs was eventually achieved.

Role of heart-rate variability in preoperative assessment of physiological reserves in patients undergoing major abdominal surgery.

BACKGROUND: Major abdominal surgery (MAS) is associated with increased morbidity and mortality. The main objective of our study was to evaluate the predictive value of heart-rate variability (HRV) concerning development of postoperative complications in patients undergoing MAS. The secondary objectives were to identify the relationship of HRV and use of vasoactive drugs during anesthesia, intensive care unit length of stay (ICU-LOS), and hospital length of stay (H-LOS). PATIENTS AND METHODS: Sixty-five patients scheduled for elective MAS were enrolled in a prospective, single-center, observational study. HRV was measured by spectral analysis (SA) preoperatively during orthostatic load. Patients were divided according to cardiac autonomic reactivity (CAR; n=23) and non-cardiac autonomic reactivity (NCAR; n=30). RESULTS: The final analysis included 53 patients. No significant difference was observed between the two groups regarding type of surgery, use of minimally invasive techniques or epidural catheter, duration of surgery and anesthesia, or the amount of fluid administered intraoperatively. The NCAR group had significantly greater intraoperative blood loss than the CAR group (541.7±541.9 mL vs 269.6±174.3 mL, p<0.05). In the NCAR group, vasoactive drugs were used during anesthesia more frequently (n=21 vs n=4; p<0.001), and more patients had at least one postoperative complication compared to the CAR group (n=19 vs n=4; p<0.01). Furthermore, the NCAR group had more serious complications (Clavien-Dindo ≥ Grade III n=6 vs n=0; p<0.05) and a greater number of complications than the CAR group (n=57 vs n=5; p<0.001). Significant differences were found for two specific subgroups of complications: hypotension requiring vasoactive drugs (NCAR: n=10 vs CAR: n=0; p<0.01) and ileus (NCAR: n=11 vs CAR: n=2; p<0.05). Moreover, significant differences were found in the ICU-LOS (NCAR: 5.7±3.5 days vs CAR: 2.6±0.7 days; p<0.0001) and H-LOS (NCAR: 12.2±5.6 days vs CAR: 7.2±1.7 days; p<0.0001). CONCLUSION: Preoperative HRV assessment during orthostatic load is objective and useful for identifying patients with low autonomic physiological reserves and high risk of poor post-operative course.

Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine.

Nicotine abuse is associated with variety of diseases including arrhythmias, most often atrial fibrillation (AF). Altered inward rectifier potassium currents including acetylcholine-sensitive current I K(Ach) are known to be related to AF pathogenesis. Since relevant data are missing, we aimed to investigate I K(Ach) changes at clinically relevant concentrations of nicotine. Experiments were performed by the whole cell patch clamp technique at 23 ± 1 °C on isolated rat atrial myocytes. Nicotine was applied at following concentrations: 4, 40 and 400 nM; ethanol at 20 mM (∼0.09%). Nicotine at 40 and 400 nM significantly activated constitutively active component of I K(Ach) with the maximum effect at 40 nM (an increase by ∼100%); similar effect was observed at -110 and -50 mV. Changes at 4 nM nicotine were negligible on average. Coapplication of 40 nM nicotine and 20 mM ethanol (which is also known to activate this current) did not show cumulative effect. In the case of acetylcholine-induced component of I K(Ach), a dual effect of nicotine and its correlation with the current magnitude in control were apparent: the current was increased by nicotine in the cells showing small current in control and vice versa. The effect of 40 and 400 nM nicotine on acetylcholine-induced component of I K(Ach) was significantly different at -110 and -50 mV. We conclude that nicotine at clinically relevant concentrations significantly increased constitutively active component of I K(Ach) and showed a dual effect on its acetylcholine-induced component, similarly as ethanol. Synchronous application of nicotine and ethanol did not cause additive effect.

Addictive drugs, arrhythmias, and cardiac inward rectifiers.

In many addictive drugs including alcohol and nicotine, proarrhythmic effects were reported. This review provides an overview of the current knowledge in this field (with a focus on the inward rectifier potassium currents) to promote the lacking data and appeal for their completion, thus, to improve understanding of the proarrhythmic potential of addictive drugs.

Patient survival, predictive factors and disease course of severe sepsis in Czech intensive care units: A multicentre, retrospective, observational study.

BACKGROUND: Severe sepsis/septic shock is associated with high mortality. In Central Europe, there is a dearth of information on the prevalence and treatment of severe sepsis. The EPOSS (Data-based Evaluation and Prediction of Outcome in Severe Sepsis) project launched in 2011 was aimed at collecting data on patients with severe sepsis/septic shock. METHODS: The EPOSS study processes data from the EPOSS project database, and is a retrospective, multicentre, observational study. This included all consecutive patients aged 18 and over who were admitted to participating ICUs from 1 January 2011 to 5 November 2013 and met the inclusion criteria of severe sepsis/septic shock. The primary endpoint was to analyse the relationship between in-hospital mortality (either in ICU or after discharge from ICU) and the type and number of fulfilled diagnostic and treatment interventions during the first 6 h after the diagnosis of severe sepsis/septic shock. RESULTS: The collected dataset involved 1082 patients meeting the criteria of severe sepsis/septic shock. Following data validation, a final dataset of 897 patients was obtained. The average age of the patient group was 64.7 years; mortality at discharge from EPOSS ICUs was 35.5% and from hospital 40.7%. Of the 10 evaluated diagnostic and treatment interventions within the initial 6 hours of identifying severe sepsis/septic shock (i.e. fulfilment of SSC bundles), four or five diagnostic and treatment interventions were administered to 58.4% patients. Combined diagnostic and treatment interventions associated with the lowest in-hospital mortality were: CVP of ≥8-12 mm Hg & MAP of ≥65 mm Hg & Urine output at ≥0.5 mL/kg/h & Lactate of ≤4.0 mmol/L & Initial lactate measured & Antibiotics in the first hour. Lactate at <4 mmol/L and MAP of ≥65 mm Hg remained statistically significant even after adjustment for patient age and APACHE II score. Statistically significantly increased in-hospital mortality was found in patients admitted from general departments (45.7%) or from other ICUs (41.6%), compared to a lower in-hospital mortality of patients transferred from outpatient clinics (26.5%) or Emergency (38.0%). Severe sepsis/septic shock patients transferred from the department of internal medicine were associated with a higher in-hospital mortality (45.1%) than surgical patients (35.5%). CONCLUSIONS: The most effective measures associated with the lowest in-hospital mortality in septic shock patients were CVP of ≥8-12 mm Hg, MAP of ≥65 mm Hg, urine output at ≥0.5 mL/kg/h, initial lactate level of ≤4.0 mmol/L and administration of antibiotics within the first hour.

[Metabolism monitoring with microdialysis in the intensive care]. / Sledování metabolismu v intenzivní péci pomocí mikrodialýzy.

Therapy of haemorrhagic shock presents a huge challenge nowadays. Changes in circulation and metabolism are preceded with changes in cells, vessels and extracellular fluid. The main disorder takes place in microcirculation. Monitoring of extracellular fluid is possible with microdialysis. This method was verified on animal models and a became base of many clinical examinations in the world. First of all it is monitoring of lactate, pyruvate, glucose and glycerole as main markers of cell metabolism. Tissue condition can be described not only with absolute values but also as relations between individual parameters e.g. lactate/pyruvate and lactate/glucose. These values do not only inform us about forthcoming change from aerobic to anaerobic metabolism but also about the degree of reperfusion. Precious information about mitochondrial dysfunction which is the essence of multiorgan dysfunction in intensive care is collected as well. Based on changes we can asses the quality of resuscitation care together with speed of shock elimination, increasing oxygen delivery and mitochondrial dysfunction treatment.

[Anticytokine therapy in sepsis and why it fails]. / Anticytokinová terapie u sepse a príciny jejího selhání.

Anticytokine therapy in sepsis belongs to a subgroup of therapeutic interventions referred to as antiinflammatory or immunomodulatory strategies in the intensive care literature. Between the mid-1980s and the late 1990s, this approach was considered very promising. Against all expectations, it proved ineffective or even harmful in many cases. However, the recent literature is suggestive of a renewed interest in the topic. Therefore, we attempted at a retrospective search for causes of the failure.