Anodic Desulfurization of Heterocyclic Thiones - A Synthesis to Imidazoles and Analogues.

An electrochemical desulfurization of 2-mercapto-imidazoles to the corresponding imidazole is established. This novel anodic transformation is bromide-mediated and easy to conduct in the simplest electrochemical setup, consisting of an undivided cell, carbon electrodes, and constant current electrolysis. The method proved successful in 14 diverse examples of imidazoles and triazoles with up to a 97% yield. The scalability was proven in the multigram synthesis of a technically relevant N-heterocyclic carbene (NHC) ligand precursor.

Evaluation of a Pre-Filled Table and a Flowchart-Based Algorithm as Cognitive Aids to Reduce Deviations in Dose Calculation for Intraoperative Red Blood Cell Transfusions in Children-An International Web-Based Simulation.

BACKGROUND: Transfusion of red blood cell concentrate can be life-saving, but requires accurate dose calculations in children. AIMS: We tested the hypothesis that cognitive aids would improve identification of the correct recommended volumes and products, according to the German National Transfusion guidelines, in pediatric transfusion scenarios. METHODS: Four online questionnaire-based scenarios, two with hemodynamically stable and two with hemodynamically unstable children, were sent to German and international pediatric anesthetists for completion. In the two stable scenarios, participants were given pre-filled tables that contained all required information. For the two emergency scenarios, existing algorithms were used and required calculation by the user. The results were classified into three categories of deviations from the recommended values (DRV): DRV120 (<80% or >120%), as the acceptable variation; DRV 300 (<33% or >300%), the deviation of concern for potential harm; and DRV 1000 (<10% or >1000%), the excessive deviation with a high probability of harm. RESULTS: A total of 1.458 pediatric anesthetists accessed this simulation questionnaire, and 402 completed questionnaires were available for analysis. A pre-filled tabular aid, avoiding calculations, led to a reduction in deviation rates in the category of DRV120 by 60% for each and of DRV300 by 17% and 20%, respectively. The use of algorithms as aids for unstable emergencies led to a reduction in the deviation rate only for DRV120 (20% and 15% respectively). In contrast, the deviation rates for DRV300 and DRV1000 rose by 37% and 16%, respectively. Participants used higher transfusion thresholds for the emergency case of a 2-year-old compromised child than for the stable case with a patient of the same age (on average, 8.6 g/dL, 95% CI 8.5-8.8 versus 7.1 g/dL, 95% CI 7.0-7.2, p < 0.001) if not supported by our aids. Participants also used a higher transfusion threshold for unstable children aged 3 months than for stable children of the same age (on average, 8.9 g/dL, 95% CI 8.7-9.0 versus 7.9 g/dL, 95% CI 7.7-8.0, p < 0.001). CONCLUSIONS: The use of cognitive aids with precalculated transfusion volumes for determining transfusion doses in children may lead to improved adherence to published recommendations, and could potentially reduce dosing deviations outside those recommended by the German national transfusion guidelines.

Evaluation of age-banded dosing of oral paracetamol in hospitalised children: a retrospective analysis using clinical data in a tertiary paediatric hospital.

OBJECTIVE: To evaluate age-banded dosing in paediatric inpatients by determining the proportion of patients whose dose would fall outside the therapeutic range (by weight). DESIGN: A retrospective observational study. Weight and height measurements and details of hospital admissions were matched from the electronic patient record of a single, tertiary paediatric hospital. Dosage which would be given according to age-banded dosing was then compared with their weight. PARTICIPANTS: All children admitted to a single tertiary children's hospital aged 3 months to 16 years over a 5-year period. Data were cleaned to remove values likely to be erroneous and filtered to reduce bias due to patients who were admitted on multiple occasions. OUTCOMES: The main outcome was the proportion of patients who would receive a subtherapeutic or supratherapeutic paracetamol dose if given a dose based on their age. Secondary outcomes were to examine this in children of different ages and to examine the impact of alternative size-based dosing strategies. RESULTS: 100 047 admissions (in 68 310 patients) had a weight documented. If age-banded dosing had been used, a subtherapeutic dose (less than 10 mg/kg) would be given during 19 829 (20%) of the admissions and a supratherapeutic dose (over 18.75 mg/kg, 75 mg/kg/day in four doses) in 4289 (4.3%). The highest risk of a subtherapeutic dose occurred in infants just prior to reaching 6 months of age (83%) and in children just prior to reaching 8 years (66%). The highest risk of a supratherapeutic dose was at 12 years of age (35%). CONCLUSION: Age-banded dosing is not suitable for an inpatient paediatric population as approximately a quarter of patients receive a dose outside the recommended range of 10.0-18.75 mg/kg.

Gastric Point-of-Care Ultrasound in Acutely and Critically Ill Children (POCUS-ped): A Scoping Review.

Introduction: Point-of-care ultrasound (POCUS) use is increasing in pediatric clinical settings. However, gastric POCUS is rarely used, despite its potential value in optimizing the diagnosis and management in several clinical scenarios (i.e., assessing gastric emptying and gastric volume/content, gastric foreign bodies, confirming nasogastric tube placement, and hypertrophic pyloric stenosis). This review aimed to assess how gastric POCUS may be used in acute and critically ill children. Materials and Methods: An international expert group was established, composed of pediatricians, pediatric intensivists, anesthesiologists, radiologists, nurses, and a methodologist. A scoping review was conducted with an aim to describe the use of gastric POCUS in pediatrics in acute and critical care settings. A literature search was conducted in three databases, to identify studies published between 1998 and 2022. Abstracts and relevant full texts were screened for eligibility, and data were extracted, according to the JBI methodology (Johanna Briggs Institute). Results: A total of 70 studies were included. Most studies (n = 47; 67%) were conducted to assess gastric emptying and gastric volume/contents. The studies assessed gastric volume, the impact of different feed types (breast milk, fortifiers, and thickeners) and feed administration modes on gastric emptying, and gastric volume/content prior to sedation or anesthesia or during surgery. Other studies described the use of gastric POCUS in foreign body ingestion (n = 6), nasogastric tube placement (n = 5), hypertrophic pyloric stenosis (n = 8), and gastric insufflation during mechanical ventilatory support (n = 4). POCUS was performed by neonatologists, anesthesiologists, emergency department physicians, and surgeons. Their learning curve was rapid, and the accuracy was high when compared to that of the ultrasound performed by radiologists (RADUS) or other gold standards (e.g., endoscopy, radiography, and MRI). No study conducted in critically ill children was found apart from that in neonatal intensive care in preterms. Discussion: Gastric POCUS appears useful and reliable in a variety of pediatric clinical settings. It may help optimize induction in emergency sedation/anesthesia, diagnose foreign bodies and hypertrophic pyloric stenosis, and assist in confirming nasogastric tube placement, avoiding delays in obtaining confirmatory examinations (RADUS, x-rays, etc.) and reducing radiation exposure. It may be useful in pediatric intensive care but requires further investigation.

Going around in circles. Is there a continuing need to use the T-piece circuit in the practice of pediatric anesthesia?

Anesthetic equipment, including breathing circuits, has evolved over time. The T-piece circuit, in its various forms, was designed to meet the needs of its time. As equipment and techniques have moved on, it is timely to consider the place of the T-piece in modern pediatric anesthetic practice. Today the circle system is a ubiquitous part of anesthesia. When integrated with a modern anesthetic machine it offers precise control of ventilation together with continuous monitoring of airway pressure and flow: but at the cost of complexity. In comparison the T-piece offers a simple cheap lightweight design, so ergonomic in use that it almost becomes part of the anesthetist: but lacks the control and the barriers to unsafe use of more sophisticated systems. In addition, it requires high fresh gas flow adding to cost and environmental pollution. This pro-con debate discusses whether there remains a case for continuing to use the T-piece circuit in preference over other options. Possible indications for the T-Piece are discussed together with alternative strategies. The limitations of the circle system, the T-piece, and other alternative (such as self-inflating resuscitator bag) are discussed with respect to pediatric anesthetic practice.

Study to evaluate the optimal dose of remifentanil required to ensure apnea during magnetic resonance imaging of the heart under general anesthesia.

BACKGROUND: Magnetic resonance (MRI) scanning of the heart is an established part of the investigation of cardiovascular conditions in children. In young children, sedation is likely to be needed, and multiple controlled periods of apnea are often required to allow image acquisition. Suppression of spontaneous ventilation is possible with remifentanil; however, the dose required is uncertain. AIMS: To establish the dose of remifentanil, by infusion, required to suppress ventilation sufficiently to allow a 30-s apnea during MRI imaging of the heart. METHOD: Patients aged 1-6 years were exposed to different doses of remifentanil, and the success in achieving a 30-s apnea was recorded. A dose recommendation was made for each patient, informed by responses of previous patients using an adaptive Bayesian dose-escalation design. Other aspects of anesthesia were standardized. A final estimate of the dose needed to achieve a successful outcome in 80% of patients (ED80) was made using logistic regression. RESULTS: 38 patients were recruited, and apnea achieved in 31 patients. The estimate of the ED80 was 0.184 µg/kg/min (95% CI 0.178-0.190). Post hoc analysis revealed that higher doses were required in younger patients. CONCLUSION: The ED80 for this indication was 0.184 µg/kg/min (95% CI 0.178-0.190). This is different from optimal dosing identified for other indications and dosing of remifentanil should be specific to the clinical context in which it is used.

Dose estimation for bivalirudin during pediatric cardiopulmonary bypass.

AIM: A typical adult-based bivalirudin regimen during cardiopulmonary bypass uses a loading dose of 1 mg kg-1 and a circuit prime (volume L × 13 mg) with a subsequent intravenous infusion 2.5 mg h-1  kg-1 . Dose in children remains unknown. We wished to determine a practical bivalirudin dosing schedule for children undergoing surgery with cardiopulmonary bypass. METHODS: Published pharmacokinetic parameters in children who were anticoagulated for cardiac catheterization using bivalirudin were compared to adult by scaling for size using allometry. An infusion regimen suitable for children was determined using a bivalirudin target concentration (13 mg L-1 ) common in adults for effect during cardiopulmonary bypass. Predicted bivalirudin infusion rates in children were compared to regimens published as case reports. RESULTS: Current pediatric bivalirudin infusion rates are based on those used in adults with titration during cardiopulmonary bypass to achieve activated clotting times longer than 400 s. Bivalirudin clearance (mL min-1  kg-1 ) can be estimated in children by scaling adult parameters using allometry. Clearance decreases through childhood and higher infusion rates in children would achieve target concentration rapidly without the need to titrate initial infusion rate. An infusion rate of 4.5 mg h-1  kg-1 in a 10 kg infant, 4 mg h-1  kg-1 in a 20 kg child and 3.5 mg h-1  kg-1 in a child 30-40 kg will target an activated clotting time slower than 400 s. Adult regimens could be used in those children heavier than 50 kg. CONCLUSION: Bivalirudin infusion in children should be started after loading dose at rates greater than those used in adults. Dose in neonates remains uncertain because neither pharmacokinetics nor coagulation pharmacodynamics have been adequately characterized.

Clinical practice guidelines in pediatric anesthesia: What constitutes high-quality guidance?

The explosion of scientific evidence has outstripped the ability of individual clinicians to acquire, process, and apply it within a clinical context. Clinical practice guidelines bridge the gap between this large body of evidence and clinical practice by translating evidence into recommendations. As such, they are an important extension of the evidence-based medicine paradigm. Guidelines promise to translate evidence into actionable clinical recommendations. However, this promise can only be realized if they are both useful and trustworthy. As the number of guidelines increases users' question their role, the quality of the scientific evidence behind them and the strength of the recommendations made. In this article, we provide definitions and outline the features of the common forms of clinical guidance. We then describe the essential characteristics of good quality clinical guidance and outline initiatives aimed at improving quality. Specific issues and limitations related to guideline development in perioperative care of children are discussed. Finally, two clinical guidance documents, published recently in Pediatric Anesthesia, are discussed based upon these criteria.

Reconstruction of Oncologic Sternectomy Defects: Lessons Learned from 60 Cases at a Single Institution.

Oncologic sternectomy results in complex defects where preoperative planning is paramount to achieve best reconstructive outcomes. Although pectoralis major muscle flap (PMF) is the workhorse for sternal soft tissue coverage, additional flaps can be required. Our purpose is to evaluate defects in which other flaps beside PMF were required to achieve optimal reconstruction. METHODS: A retrospective review of consecutive patients at our institution who underwent reconstruction after sternal tumor resection was performed. Demographics, surgical characteristics, and outcomes were evaluated. Further analysis was performed to identify defect characteristics where additional flaps to PMF were needed to complete reconstruction. RESULTS: In 11 years, 60 consecutive patients were identified. Mean age was 58 (28-81) years old, with a mean follow-up of 40.6 (12-64) months. The majority were primary sternal tumors (67%) and the mean defect size was 148 cm2 (±81). Fourteen (23%) patients presented with postoperative complications, and the 30-day mortality rate was 1.6%. In 19 (32%) cases, additional flaps were required; the most common being the rectus abdominis muscle flaps. Larger thoracic defects (P = 0.011) and resections involving the inferior sternum (P = 0.021) or the skin (P = 0.011) were more likely to require additional flaps. CONCLUSIONS: Reconstruction of oncologic sternal defects requires a multidisciplinary team approach. Larger thoracic defects, particularly those that involve the skin and the inferior sternum, are more likely to require additional flaps for optimal reconstruction.

Patterns of Instability Associated With Endotracheal Suctioning in Infants With Single-Ventricle Physiology.

BACKGROUND: In infants with single-ventricle physiology, endotracheal suctioning poses risks because of the instability between pulmonary and systemic blood flow. OBJECTIVE: To examine processes and adverse events associated with endotracheal suctioning in the first 48 hours after 3 surgical procedures: the Norwood or Norwood-Sano procedure, pulmonary artery banding, and the modified Blalock-Taussig shunt. METHODS: Prospective observational study in a pediatric intensive care unit. RESULTS: Bedside nurses collected data from 211 episodes of endotracheal suctioning in 24 infants. Most (62%,130/211) suction episodes were unplanned; 38% (81/211) were planned. The most common reason for unplanned suctioning was arterial desaturation (48%, 62/130 episodes). The infants' oxygen saturation levels before suctioning ranged from 27% to 86%. Serious adverse events occurred in 9% (19/211) of suction episodes. In 8 (42%) of the episodes involving a serious adverse event, the patient received no additional intravenous bolus of analgesic or muscle relaxant before suctioning; in 8 episodes (42%), the patient received both an analgesic and a relaxant; in 3 episodes (16%), the patient received either an analgesic or a relaxant but not both. More adverse events occurred with open suctioning (68%, 13/19) than with closed suctioning (32%, 6/19). Most adverse events (68%, 13/19) occurred during the night shift. CONCLUSIONS: Significant hemodynamic instability and adverse events occur during routine suctioning in infants with single-ventricle physiology after surgical palliation.

Pilot Study Comparing Closed Versus Open Tracheal Suctioning in Postoperative Neonates and Infants With Complex Congenital Heart Disease.

OBJECTIVES: To determine the hemodynamic effect of tracheal suction method in the first 36 hours after high-risk infant heart surgery on the PICU and to compare open and closed suctioning techniques. DESIGN: Pilot randomized crossover study. SETTING: Single PICU in United Kingdom. PARTICIPANTS: Infants undergoing surgical palliation with Norwood Sano, modified Blalock-Taussig shunt, or pulmonary artery banding in the first 36 hours postoperatively. INTERVENTIONS: Infants were randomized to receive open or closed (in-line) tracheal suctioning either for their first or second study tracheal suction in the first 36 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Twenty-four infants were enrolled over 18 months, 11 after modified Blalock-Taussig shunt, seven after Norwood Sano, and six after pulmonary artery banding. Thirteen patients received the open suction method first followed by the closed suction method second, and 11 patients received the closed suction method first followed by the open suction method second in the first 36 hours after their surgery. There were statistically significant larger changes in heart rate (p = 0.002), systolic blood pressure (p = 0.022), diastolic blood pressure (p = 0.009), mean blood pressure (p = 0.007), and arterial saturation (p = 0.040) using the open suction method, compared with closed suctioning, although none were clinically significant (defined as requiring any intervention). CONCLUSIONS: There were no clinically significant differences between closed and open tracheal suction methods; however, there were statistically significant greater changes in some hemodynamic variables with open tracheal suctioning, suggesting that closed technique may be safer in children with more precarious physiology.

The changing paradigm of the doctor-patient relationship: Montgomery v Lanarkshire Health Board and developments in the 'duty to warn'.

The standard of risk disclosure required in New Zealand and the UK has differed until recently. Medical practitioners who perform treatment without adequate disclosure run the risk of violating patients' rights, and fail to practice at the high level reasonably expected of them. Before Montgomery v Lanarkshire Health Board, it was the case in the UK that a practitioner need not disclose a particular risk of treatment if a qualified body of medical opinion would also not have disclosed that risk. In this viewpoint, we examine the change brought about by Montgomery, and its implications for New Zealand practitioners.

Near-infrared spectroscopy after high-risk congenital heart surgery in the paediatric intensive care unit.

OBJECTIVE: To establish whether the use of near-infrared spectroscopy is potentially beneficial in high-risk cardiac infants in United Kingdom paediatric intensive care units. DESIGN: A prospective observational pilot study. SETTING: An intensive care unit in North West England. PATIENTS: A total of 10 infants after congenital heart surgery, five with biventricular repairs and five with single-ventricle physiology undergoing palliation. INTERVENTIONS: Cerebral and somatic near-infrared spectroscopy monitoring for 24 hours post-operatively in the intensive care unit. MEASUREMENT AND MAIN RESULTS: Overall, there was no strong correlation between cerebral near-infrared spectroscopy and mixed venous oxygen saturation (r=0.48). At individual time points, the correlation was only strong (r=0.74) 1 hour after admission. The correlation was stronger for the biventricular patients (r=0.68) than single-ventricle infants (r=0.31). A strong inverse correlation was demonstrated between cerebral near-infrared spectroscopy and serum lactate at 3 of the 5 post-operative time points (1, 4, and 12 hours: r=-0.76, -0.72, and -0.69). The correlation was stronger when the cerebral near-infrared spectroscopy was <60%. For cerebral near-infrared spectroscopy <60%, the inverse correlation with lactate was r=-0.82 compared with those cerebral near-infrared spectroscopy >60%, which was r=-0.50. No correlations could be demonstrated between (average) somatic near-infrared spectroscopy and serum lactate (r=-0.13, n=110) or mixed venous oxygen saturation and serum lactate. There was one infant who suffered a cardiopulmonary arrest, and the cerebral near-infrared spectroscopy showed a consistent 43 minute decline before the event. CONCLUSIONS: We found that cerebral near-infrared spectroscopy is potentially beneficial as a non-invasive, continuously displayed value and is feasible to use on cost-constrained (National Health Service) cardiac intensive care units in children following heart surgery.

Coagulation and the surgical neonate.

Both coagulopathy and abnormal thrombosis can complicate the anesthetic and surgical management of neonatal patients; however, the patterns of bleeding and thrombosis in neonates differ from those in adults or older children. Severe coagulopathic bleeding most commonly occurs during heart surgery and almost certainly contributes to morbidity and mortality in this population. Such severe bleeding is rare during other surgery; the exception is babies presenting to the operating room with established coagulopathy secondary to severe sepsis. Alternatively, pathological thrombosis will mainly occur in association with indwelling vascular access devices or surgically created vascular shunts. There are important differences between the coagulation system in neonates and older patients. The implication of this is that therapies established in other patient groups will not be optimal for neonates without adaptation. While evidence from high-quality clinical trials is rarely available, an understanding of how coagulation in neonates differs can help to guide practice. This review will discuss important differences between the coagulation system of neonates and older patients and how these relate to newer models of coagulation. The emphasis will be on issues likely to impact on perioperative care. In particular, the management of severe bleeding, the manipulation of coagulation during heart surgery, and the management of coagulopathy in septic neonates will be discussed in detail.

Phase IIb/III dose ranging study of tamsulosin as treatment for children with neuropathic bladder.

PURPOSE: We evaluated the efficacy and safety of tamsulosin hydrochloride in children with increased detrusor leak point pressure associated with neuropathic bladder. MATERIALS AND METHODS: In a double-blind, randomized, placebo controlled trial patients with detrusor leak point pressure 40 cm H(2)O or greater were stratified by age (2 to less than 5 years, 5 to less than 10 years, 10 to 16 years) and concomitant anticholinergic use, and were randomized to receive various doses of tamsulosin or placebo. A 2-week titration was followed by a 12-week maintenance treatment period. Primary end point was response, ie detrusor leak point pressure less than 40 cm H(2)O from 2 evaluations on the same day at week 14. Secondary end points included detrusor leak point pressure change from baseline, hydronephrosis and hydroureter responses, change in catheterization volumes and adverse events. RESULTS: A total of 161 patients received 1 or more treatment doses between January 2008 and February 2009, and 135 were evaluable for the primary end point. A total of 51 patients (37.8%) were detrusor leak point pressure responders, with no statistically significant difference in response rates between each tamsulosin dose and placebo. Adjusting for stratification variables, mean detrusor leak point pressure changes from baseline to week 14 for placebo and low, medium and high dose groups were -11.4, -17.6, -4.6 and -14.3 cm H(2)O, respectively. In 141 evaluable patients hydroureter/hydronephrosis improvement rates were 7.1% and 5.7% in left and right kidneys (hydroureter), respectively, and 14.9% and 14.2% in left and right kidneys (hydronephrosis), respectively. No group experienced decreases in median post-void residual volume at week 14. Drug related adverse event incidences were 4.9% (placebo) and 5.8% (tamsulosin). CONCLUSIONS: Tamsulosin was well tolerated but not efficacious in this pediatric population with neuropathic bladder.

Bovine jugular vein valved conduit: up to 10 years follow-up.

OBJECTIVE: The present study evaluated the mortality and conduit failure in bovine jugular vein (BJV) conduits. METHODS: Between October 1999 and February 2009, 193 patients (mean age, 6.7 ± 5.8 years; range, 5 days to 18 years; mean weight, 23.9 ± 21.0 kg; range, 2.4-105.4 kg) had been discharged after BJV implantation. The reason for BJV implantation was right ventricular outflow tract reconstruction in 117 conduit replacement in 44, and the Ross procedure in 32. The diameter of the BJV was 12 mm in 18 patients (9.3%), 14 mm in 16 (8.3%), 16 mm in 42 (21.7%), 18 mm in 37 (19.2%), 20 mm in 15 (7.8%), and 22 mm in 65 (33.7%). RESULTS: At a mean ± SD follow-up of 4.6 ± 2.3 y/patient (range, 8 months to 10 years), 5 late deaths (2.6%) had occurred, all unrelated to conduit failure. Conduit-related problems required an interventional procedure as the first treatment in 10 patients (5.2%) within a mean interval of 2.5 ± 1.4 years (range, 8 months to 5.3 years) or surgical revision in 5 patients (2.6%) after 2.1 ± 1.9 years (range, 19 days to 4.1 years). Late deaths occurred in 5.9% (2/34) of patients with a BJV size of 12 to 14 mm versus 1.9% (3/159) in patients with a size of 16 to 22 mm (P = NS). An interventional procedure or surgical revision was required in 29.4% (10/34) of patients with a BJV size of 12 to 14 mm versus 3.1% (5/159) in patients with a size of 16 to 22 mm (P < .0005). CONCLUSIONS: After 10 years of experience with the BJV, this conduit has remained a reliable alternative to pulmonary homografts with respect to survival and freedom from conduit failure. However, the incidence was greater and the presentation of conduit failure was earlier in patients with a smaller size BJV conduit (12-14 mm).

Treatment and monitoring of coagulation abnormalities in children undergoing heart surgery.

Bleeding is a considerable clinical problem during and after pediatric heart surgery. While the primary cause of bleeding is surgical trauma, its treatment is often complicated by the presence of coagulopathy. The principle causes of coagulopathy are discussed to provide a context for treatment. The role of laboratory and point of care tests, which aim to identify the cause of bleeding in the individual patient, is also discussed. An attempt is made to examine the current evidence for available therapies, including use of blood products and, more recently proposed, approaches based on human or recombinant factor concentrates.