Anaesthesia in  SARS-CoV-2 infected children - single-centre experience. A case-control study.

INTRODUCTION: Although manifestation of SARS-CoV-2 infection in children is gene-rally mild or asymptomatic, anaesthetic implications of the infection in children are still a matter of concern. Single reports suggest that patients with SARS-CoV-2 infection are at higher risk of anaesthetic complications. MATERIAL AND METHODS: We performed a retrospective, case control study analysing the risk of general anaesthesia in SARS-CoV-2 infected children admitted to a tertiary paediatric university hospital for the purpose of urgent procedures requiring anaesthesia  between April 1st and September 30 th , 2021. The control group consisted of  SARS-CoV-2 negative children consecutively anaesthetised for the same reasons during the first month of observation. Our hypothesis was: general anaesthesia can be safely performed in SARS-CoV-2 infected children. Study endpoints: primary - anaesthetic respiratory complications (bronchospasm, laryngospasm, intraoperative desaturation below 94%, desaturation below 94% after awakening, unplanned postoperative mechanical ventilation); secondary - hospital length of stay, thrombotic, cardiac, haemorrhagic events, ICU admission, deaths during hospitalisation. RESULTS: The examined group consisted of 58 SARS-CoV-2 infected children, the matched control group of 198 patients. The rate of complications in both groups was very low, with no significant difference between the groups. The only differences observed were a higher frequency of desaturations in the awakening period and longer time of hospitalisation in SARS-CoV-2 infected patients. Multivariate logistic regression analysis showed that physical status of the patient and duration of the procedure were the main factors influencing the risk of complications. CONCLUSIONS: In our experience anaesthesia of SARS-CoV-2 infected children can be safely performed.

Impact of lidocaine on hemodynamic and respiratory parameters during laparoscopic appendectomy in children.

We assessed the influence of systemic lidocaine administration on ventilatory and circulatory parameters, and the pneumoperitoneum impact on the cardiopulmonary system during a laparoscopic appendectomy in children. A single-center parallel single-masked randomized controlled study was carried out with 58 patients (3-17 years). Intravenous lidocaine bolus of 1.5 mg/kg over 5 min before induction of anesthesia followed by lidocaine infusion at 1.5 mg/kg/h intraoperatively. Respiratory system compliance (C, C/kg), Ppeak-PEEP and Pulse rate (Pulse), systolic, diastolic and mean blood pressure (NBPs, NBPd, NBPm), assessed in the Lidocaine and Control group, at the: beginning (P1), minimum lung compliance (P2) and at the end of surgery (P3) were compared. The respiratory/hemodynamic parameters did not differ between the groups at any stage of operation. Blood Pressure and Ppeak-PEEP were significantly higher at the P2 compared to P1 and P3 stages (P < 0.001, 1 - ß ≥ 0.895) that correlated with lung compliance changes: C/kg vs. NBPs and Ppeak-PEEP (- 0.42, - 0.84; P < 0.001); C vs. Pulse and Ppeak-PEEP (- 0.48, - 0.46; P < 0.001). Although an increase in intraabdominal pressure up to 12(15) mmHg causes significant changes in hemodynamic/respiratory parameters, there appears to be no risk of fatal reactions in 1E, 2E ASA patients. Systemic lidocaine administration doesn't alleviate circulatory/respiratory alterations during pneumoperitoneum. No lidocaine related episode of anaphylaxis, systemic toxicity, circulatory disturbances or neurological impairment occurred.ClinicalTrials.gov: 22/03/2019.Trial registration number: NCT03886896.

Value of troponin T measurements for prediction of postoperative course and length of ICU stay of children after surgical correction of congenital heart disease.

BACKGROUND: The development of surgical and anaesthetic techniques improved the outcomes in children with congenital heart disease (CHD). After repair of defects using cardiopulmonary bypass (CPB) children often require prolonged respiratory or inotropic support in the intensive care unit (ICU). The aim of the study was to assess troponin T (TnT) values as a predictor of postoperative requirements and ICU length of stay (ICU-LOS) after cardiac surgery. METHODS: We included 41 patients who underwent corrective surgery for CHD between August and December 2017. TnT level was measured after induction of anaesthesia, 12 h after CPB (t2) and 24 h following CPB (t3). The Aristotle Basic Score for procedure complexity was calculated, total times of CPB and aortic cross-clamping were measured, and maximal Vasoactive-Inotropic Score and ICU-LOS were determined. Statistical relationships between TnT levels and the mentioned parameters were estimated. RESULTS: The median age of the patients was 37 months (14 days to 17 years). Three patients died. The median ICU-LOS was 42.7 hours. A positive correlation was found between ICU-LOS and TnT values at t2 ( Rs = 0.62, P = 0.008) and t3 ( Rs = 0.44, P = 0.018). TnT concentrations at t2 correlated significantly with: Aristotle score ( Rs = 0.50, P = 0.001), total time of CPB ( R s =0.58, P = 0.001), CC time ( Rs = 0.47, P = 0.002) and VIS ( Rs = 0.42, P = 0.001). TnT levels did not discriminate between survivors and non-survivors. CONCLUSIONS: Troponin T concentration is a useful tool to anticipate postoperative course and ICU-LOS in children after cardiac surgery.

The case of fatal acute hemorrhagic necrotizing encephalitis in a two-month-old boy with Covid-19.

SARS-CoV-2 infection in healthy children is usually benign. However, severe, life-threatening cases have previously been reported, notably in infants. We must be aware that data on the natural history of COVID-19 are still full of gaps, especially as far as the pediatric population is concerned. Therefore, it is important to describe rare manifestations of SARS-CoV-2 acute infection in children. Here we present the case of acute hemorrhagic necrotizing encephalitis (AHNE) in a previously healthy, 2-month-old male infant with SARS-CoV-2 infection. After 2 days of fever with signs of respiratory tract infection, neurological manifestations appeared: irritability, nystagmus, agitation then apathy. As a consequence of apnea, he required emergent intubation and was transferred to our PICU. Brain MRI revealed diffuse areas of oedema associated with numerous symmetrical changes with punctate hemorrhages in basal ganglia, thalami, brainstem, and cerebral gray matter. CSF was clear with pleocytosis 484 cells/µl, elevated lactic acid and protein. Despite broad microbiological testing, only SARS-CoV2 was detected in PCR nasal swab. Therefore, acute hemorrhagic necrotizing encephalitis (AHNE) as a result of COVID-19 was the most probable diagnosis. The outcome was unfavorable - brain death was confirmed, life support was withdrawn.

Invitation to participate in a multi-center study for validation of cerebral computed tomography angiography and computed tomography perfusion in the determination of cerebral circulatory arrest during brain death/death by neurological criteria diagnosis procedure in paediatric population below 12 years of age.

We would like to invite paediatric intensive care units (PICU) to join our multi-center trial concerning patient population < 12 y/o and aiming at: • validation of computed tomography angiography (CTA)/computed tomography perfusion (CTP) tests for brain death/death by neurological criteria (BD/DNC) diagnosis procedures, • validation of duplex Doppler insonation of extracranial segments of the internal cerebral arteries and the vertebral arteries for choosing an optimal time for CTA/CTP testing.

Efficacy of intravenous lidocaine infusions for pain relief in children undergoing laparoscopic appendectomy: a randomized controlled trial.

Intravenous lidocaine, a potent local anesthetic with analgesic and anti-inflammatory properties, has been shown to be an effective adjunct that reduces intra- and postoperative opioid consumption and facilitates pain management in adults. While it shows promise for use in the pediatric population, limited evidence is available. OBJECTIVES: To determine if general anesthesia with intraoperative intravenous lidocaine infusion versus general anesthesia without intravenous lidocaine infusion in children undergoing laparoscopic appendectomy decreased opioid requirements intra- and postoperatively. DESIGN: A single-center parallel single-masked randomized controlled study. A computer-generated blocked randomization list was used to allocate participants. The study was conducted between March 2019 and January 2020. SETTING: Pediatric teaching hospital in Poland. PARTICIPANTS: Seventy-four patients aged between 18 months and 18 years undergoing laparoscopic appendectomy. Seventy-one patients fulfilled the study requirements. INTERVENTION: Intravenous lidocaine bolus of 1.5 mg/kg over 5 min before induction of anesthesia followed by lidocaine infusion at 1.5 mg/kg/h intraoperatively. The infusion was discontinued before the patients' transfer to the postanesthesia care unit (PACU). PRIMARY OUTCOME MEASURE: The primary outcome measure was total nalbuphine requirement in milligrams during the first 24 h after surgery. SECONDARY OUTCOME MEASURES: The secondary outcome measures were intraoperative fentanyl consumption, intraoperative sevoflurane consumption, time to the first rescue analgesic request, incidence of postoperative nausea and vomiting during the first 24 h after surgery, frequency of side effects of lidocaine. RESULTS: Children (n = 74) aged 5-17 randomly allocated to receive intraoperative lidocaine infusion (n = 37) or no intervention (n = 37). Seventy-one were included in the analysis (35 in the study group and 36 in the control group). There was no difference in the cumulative dose of nalbuphine in the first 24 h after removal of the endotracheal tube between groups [median of 0.1061 (IQR: 0.0962-0.2222) mg/kg in the lidocaine group, compared to the control group median of 0.1325 (IQR: 0.0899-0.22020) mg/kg, p = 0.63]. Intraoperative fentanyl consumption was lower in the lidocaine group [median of 5.091 (IQR: 4.848-5.714) µg/kg] than in the control group [median of 5.969 (IQR: 5.000-6.748), p = 0.03]. Taking into account the additional doses administered based on clinical indications, the reduction in the requirement for fentanyl in the lidocaine group was even greater [median of 0.0 (IQR: 0.0-0.952) vs 0.99 (IQR: 0.0-1.809) µg/kg, p = 0.01]. No difference was observed in the sevoflurane consumption between the two groups [median of 32.5 ml (IQR 25.0-43.0) in the lidocaine group vs median of 35.0 ml (IQR: 23.5-46.0) in the control group, p = 0.56]. The time to first analgesic request in the lidocaine group was prolonged [median of 55 (IQR: 40-110) min in the lidocaine group vs median of 40.5 (IQR: 28-65) min in the control group, p = 0.05]. There was no difference in the frequency of PONV between the two groups (48.57% in the lidocaine group vs 61.11% in the control group, p = 0.29). No lidocaine related incidence of anaphylaxis, systemic toxicity, circulatory disturbances or neurological impairment was reported, during anesthesia or postoperative period. CONCLUSIONS: Intraoperative systemic lidocaine administration reduced the intraoperative requirement for opioids in children undergoing laparoscopic appendectomy. This effect was time limited, and hence did not affect opioid consumption in the first 24 h following discontinuation of lidocaine infusion. TRIAL REGISTRATION: NCT03886896 .

Combination of neuraxial and peripheral regional anaesthetic techniques in a multimodal analgesia regimen - case report.

Choosing the right anaesthetic technique and postoperative analgesia after major surgery can be a great challenge for paediatric anaesthetists, especially when younger children are concerned. The simultaneous use of systemic analgesics with adjuncts in combination with single-shot blocks performed at the right time may facilitate the patient's recovery and result in a comfortable postoperative period.

Perioperative thromboembolism prophylaxis in children - is it necessary?

Perioperative antithrombotic prophylaxis in adults is widely recommended. In the past, it was believed that this does not concern the paediatric population. Recently, however, there has been growing evidence that the incidence of venous thromboembolism (VTE) in children is increasing and is probably underestimated. This is a result of advances in treatment of previously lethal conditions, wide use of central venous catheters, and improved awareness and diagnosis of VTE complications. However, large clinical trials assessing the efficacy and safety of antithrombotic treatment in children have not been conducted and there are not widely accepted protocols of perioperative prophylaxis. At the same time, there is a growing awareness of its sequelae: compartment syndrome, pulmonary embolism, pulmonary hypertension, post-thrombotic syndrome, cost, length of hospital stay, and mortality. Local recommendations based on observational studies, individual experience, and extrapolation from data of adults have emerged.

Factors involved in initiation and regulation of complement lectin pathway influence postoperative outcome after pediatric cardiac surgery involving cardiopulmonary bypass.

Congenital heart disease (CHD) often requires surgical intervention, and is sometimes associated with life-threatening post-operative complications. We have investigated some factors of the innate immune system involved in the initiation or regulation of complement lectin pathway activation (MASP-1, MASP-2 MASP-3, MAp19, MAp44, ficolin-3) and related them to complications and prognosis in 190 pediatric patients undergoing CHD repair with the use of cardiopulmonary bypass (CPB). Patients with MAp44 levels ≤1.81 µg/ml more frequently experienced low cardiac output syndrome (LCOS), renal insufficiency, systemic inflammatory response syndrome (SIRS) and multiorgan dysfunction (MODS). Low MASP-3 (≤5.18 µg/ml) and high MASP-1 (≥11.7 µg/ml) levels were often associated with fatal outcome. Low ficolin-3 concentrations (≤10.1 µg/ml) were more common among patients experiencing SIRS and MODS than in those without complications. However, patients suffering from SIRS and MODS with low ficolin-3 had a much better prognosis (91% survival vs. 37% among other patients; p = 0.007). A discriminating value of 12.7 µg/ml ficolin-3 yielded 8% vs. 60% mortality (p = 0.001). Our data extend the knowledge concerning involvement of proteins of the lectin pathway in development of post-CPB complications. The potential prognostic value of low preoperative MAp44 and high preoperative ficolin-3 seems promising and warrants independent confirmation.

Deposition of mannose-binding lectin and ficolins and activation of the lectin pathway of complement on the surface of polyurethane tubing used for cardiopulmonary bypass.

The artificial surface used for cardiopulmonary bypass (CPB) is a crucial factor activating the complement system and thus contributing to the generation of a systemic inflammatory response. The activation of classical and alternative pathways on this artificial surface is well known. In contrast, lectin pathway (LP) activation has not been fully investigated, although noted during CPB in several studies. Moreover, we have recently proved the contribution of the LP to the generation of the systemic inflammatory response syndrome after pediatric cardiac surgery. The aim of this study was to assess LP-mediated complement activation on the surface of polyurethane CPB circuit tubing (noncoated Chalice ® ), used for CPB procedures in children with congenital heart disease. We found deposition of mannose-binding lectin, ficolin-1, -2, and -3 on the surface of unused tubing and on tubing used for CPB from a small minority of patients. Furthermore, we observed deposition of complement C4 activation products on tubing used for CPB and previously unused tubing after incubation with normal serum. The latter finding indicates LP activation in vitro on the polyurethane surface. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1202-1208, 2018.

Mannose-binding lectin (MBL) insufficiency protects against the development of systemic inflammatory response after pediatric cardiac surgery.

We investigated MBL2 and MASP2 genotypes, serum MBL (mannose-binding lectin) levels and activities of its complexes with associated serine proteases (MASP-1, MASP -2), in relation to complications following cardiac surgery in 195 children. The incidence of SIRS was lower in patients carrying MBL2 A/O and O/O genotypes (p=0.024). Children with MBL levels <500ng/ml had a lower risk of SIRS (p=0.014) and fever (p=0.044). Median MBL concentration was higher in patients who developed SIRS (p=0.048) but lower in those with post-operative infections (p=0.046). MBL-MASP-2 activities <100mU/ml protected from SIRS (p=0.007), low cardiac output syndrome (p=0.03) and multiorgan failure (p=0.012). In contrast, MBL2 YA/YA genotypes were associated with SIRS (p=0.018), low cardiac output syndrome (p=0.018), fever (p=0.018) and high inotropic score (VIS>30) (p=0.021). Thus, low MBL concentrations and associated genotypes may protect patients from systemic inflammation while high MBL serum levels and corresponding genotypes are risk factors of postoperative complications.

Primary Ficolin-3 deficiency--Is it associated with increased susceptibility to infections?

Ficolin-3 (also called H-ficolin or Hakata antigen) is the most potent activator of the lectin pathway of complement in vitro. Its genetically determined deficiency in Caucasians is associated with a frame-shift mutation +1637delC (rs28357092) of the FCN3 gene. When it was described for the first time, it was postulated to be strictly associated with enhanced susceptibility to infections. At present, with our knowledge extended by several other patients that issue seems to be more complicated and less clear-cut. Two new cases of primary Ficolin-3 deficiency are reported here: a 50-year old male, suffering from membranous nephropathy and an 11-month old male infant who was operated on to repair congenital heart disease. Based on those cases and a literature review, we conclude that the clinical consequences of congenital Ficolin-3 deficiency are still unclear and such questions as whether it may be life-threatening or acts as a disease modifier remain to be elucidated.

Mannan-binding lectin in cardiovascular disease.

Cardiovascular disease remains the leading cause of mortality and morbidity worldwide so research continues into underlying mechanisms. Since innate immunity and its potent component mannan-binding lectin have been proven to play an important role in the inflammatory response during infection and ischaemia-reperfusion injury, attention has been paid to its role in the development of cardiovascular complications as well. This review provides a general outline of the structure and genetic polymorphism of MBL and its role in inflammation/tissue injury with emphasis on associations with cardiovascular disease. MBL appears to be involved in the pathogenesis of atherosclerosis and, in consequence, coronary artery disease and also inflammation and tissue injury after myocardial infarction and heart transplantation. The relationship between MBL and disease is rather complex and depends on different genetic and environmental factors. That could be why the data obtained from animal and clinical studies are sometimes contradictory proving not for the first time that innate immunity is a "double-edge sword," sometimes beneficial and, at other times disastrous for the host.

Use of recombinant activated factor VII for controlling refractory postoperative bleeding in children undergoing cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: To review the efficacy, safety, and dose of recombinant activated factor VII in off-label management of refractory bleeding in pediatric patients with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass. DESIGN: A retrospective database analysis with medical records review. SETTING: A single research hospital. PARTICIPANTS: Ninety pediatric patients with uncontrolled postoperative hemorrhage after cardiac surgery with cardiopulmonary bypass for congenital heart disease. INTERVENTIONS: Intravenous recombinant activated factor VII treatment according to institutional treatment protocol. MEASUREMENTS AND MAIN RESULTS: The recombinant activated factor VII treatment was effective in reducing bleeding in 78 pediatric patients. The 12 patients who failed to respond had surgical sources of bleeding. The mean blood loss decreased from 51.04 mL/kg/2 h to 7.8 mL/kg/2 h (p < 0.001) in neonates, from 40.2 mL/kg/2 h to 7.7 mL/kg/2 h (p < 0.001) in infants, and from 29.1 mL/kg/2 h to 4.0 mL/kg/2 h in children (p < 0.001). The mean (standard deviation) total recombinant activated factor VII doses required to achieve hemostasis were 131.7 (69.8) µg/kg in neonates, 104.6 (36.0) µg/kg in infants, and 44.6 (15.3) µg/kg in children aged 1 to ≤18 years. There was no evidence of thrombosis in the first 24 hours after the administration of recombinant activated factor VII. CONCLUSIONS: Recombinant activated factor VII treatment reduced blood loss and transfusion requirements and prevented re-exploration in the majority (83.8%) of pediatric cardiac surgery patients. High doses were required to discontinue bleeding promptly in neonates, the majority of whom had hypoplastic left-heart syndrome. No treatment-related thrombotic events were observed.

Predictors of long intensive care unit stay following cardiac surgery in children.

OBJECTIVE: Prolonged length of stay in intensive care units after congenital heart disease surgery is associated with poor outcome, places a considerable burden on the financial resources of hospitals, and is an organizational challenge as well. This research discusses the impact of perioperative factors on prolonged stay in intensive care units. METHODS: This is a retrospective study examining the determinants of prolonged intensive care length of stay in 693 children after cardiac surgery. Univariate and multivariate analyses were performed for an intensive care unit stay over 3 and over 14 days. RESULTS: Neonatal age, preoperative mechanical ventilation and preoperative myocardial dysfunction, complexity and duration of procedures, as well as postoperative complications (low cardiac output syndrome, bleeding, re-operation, acute kidney injury, sepsis, respiratory insufficiency, pulmonary hypertension, pneumothorax, postoperative cardiac arrest, pneumonia, and delayed sternum closure) prolong intensive care unit hospitalization over 3 days. Patients with acute kidney injury requiring renal replacement therapy, pneumothorax, pulmonary hypertension, need for re-operation during the same admission, and myocardial dysfunction prior to surgery are at high risk of intensive care unit stay over 14 days. CONCLUSIONS: Some patients with a risk of prolonged hospitalization may be identified preoperatively, the others just after the operation. Optimizing preoperative status and aggressive treatment of complications may have significant influence on the duration of hospitalization in intensive care units. The knowledge of risk factors may facilitate organizational procedures and rational bed management.

[The use of hypothermia in intensive therapy]. / Zastosowanie hipotermii kontrolowanej w intensywnej terapii.

The authors discuss the usefulness of therapeutic hypothermia for neuroprotection in patients with hypoxic cerebral damage. Although first reports on this method were published more than 50 years ago, it gained wider popularity at the end of 20th century. This popularity was related to the fact that deep hypothermia (below 30 degrees C) was displaced by mild hypothermia using higher temperatures (32-35 degrees C). The therapeutic benefit of mild hypothermia is based on the decrease of cerebral metabolism (5-7% per one degree Celsius). The ATP consumption by neurons is decreased despite the lack of glucose and oxygen associated with cardiac arrest, and membrane function is longer preserved. Hypothermia also prevents cerebral oedema, both of vascular and cytotoxic origin, and other reactions associated with reperfusion injury. Recently, the American Heart Association and European Resuscitation Council recommended the use of mild hypothermia (32-34 degrees C) in adult patients after ventricular fibrillation. Some clinical data also indicates that induced hypothermia reduces cerebral hypoxic ischemic injury. Randomized clinical trials in newborns with hypoxic ischemic encephalopathy confirm improved neurological outcomes and survival at 18 months of age with therapeutic hypothermia. The use of hypothermia after craniocerebral and spinal trauma, or ischemic brain damage is controversial, and not widely recommended. The authors describe various methods of inducing hypothermia in clinical settings; perhaps the most effective is intravenous infusion of cold fluids together with superficial cooling. Side effects and complications are discussed. They conclude that mild hypothermia can be regarded as a useful therapy in adult patients after VF cardiac arrest, and in neonates with hypoxic cerebral brain damage.