Efficacy of a hybrid technique of simultaneous videolaryngoscopy with flexible bronchoscopy in children with difficult direct laryngoscopy in the Pediatric Difficult Intubation Registry.

Children with difficult tracheal intubation are at increased risk of severe complications, including hypoxaemia and cardiac arrest. Increasing experience with the simultaneous use of videolaryngoscopy and flexible bronchoscopy (hybrid) in adults led us to hypothesise that this hybrid technique could be used safely and effectively in children under general anaesthesia. We reviewed observational data from the international Pediatric Difficult Intubation Registry from 2017 to 2021 to assess the safety and efficacy of hybrid tracheal intubation approaches in paediatric patients. In total, 140 patients who underwent 180 attempts at tracheal intubation with the hybrid technique were propensity score-matched 4:1 with 560 patients who underwent 800 attempts with a flexible bronchoscope. In the hybrid group, first attempt success was 70% (98/140) compared with 63% (352/560) in the flexible bronchoscope group (odds ratio (95%CI) 1.4 (0.9-2.1), p = 0.1). Eventual success rates in the matched groups were 90% (126/140) for hybrid vs. 89% (499/560) for flexible bronchoscope (1.1 (0.6-2.1), p = 0.8). Complication rates were similar in both groups (15% (28 complications in 182 attempts) hybrid; 13% (102 complications in 800 attempts) flexible bronchoscope, p = 0.3). The hybrid technique was more likely than flexible bronchoscopy to be used as a rescue technique following the failure of another technique (39% (55/140) vs. 25% (138/560), 2.1 (1.4-3.2) p < 0.001). While technically challenging, the hybrid technique has success rates similar to other advanced airway techniques, few complications and may be considered an alternative technique when developing an airway plan for paediatric patients whose tracheas are difficult to intubate under general anaesthesia.

Complications associated with paediatric airway management during the COVID-19 pandemic: an international, multicentre, observational study.

Respiratory adverse events in adults with COVID-19 undergoing general anaesthesia can be life-threatening. However, there remains a knowledge gap about respiratory adverse events in children with COVID-19. We created an international observational registry to collect airway management outcomes in children with COVID-19 who were having a general anaesthetic. We hypothesised that children with confirmed or suspected COVID-19 would experience more hypoxaemia and complications than those without. Between 3 April 2020 and 1 November 2020, 78 international centres participated. In phase 1, centres collected outcomes on all children (age ≤ 18 y) having a general anaesthetic for 2 consecutive weeks. In phase 2, centres recorded outcomes for children with test-confirmed or suspected COVID-19 (based on symptoms) having a general anaesthetic. We did not study children whose tracheas were already intubated. The primary outcome was the incidence of hypoxaemia during airway management. Secondary outcomes included: incidence of other complications; and first-pass success rate for tracheal intubation. In total, 7896 children were analysed (7567 COVID-19 negative and 329 confirmed or presumed COVID-19 positive). The incidence of hypoxaemia during airway management was greater in children who were COVID-19 positive (24 out of 329 (7%) vs. 214 out of 7567 (3%); OR 2.70 (95%CI 1.70-4.10)). Children who had symptoms of COVID-19 had a higher incidence of hypoxaemia compared with those who were asymptomatic (9 out of 51 (19%) vs. 14 out of 258 (5%), respectively; OR 3.7 (95%CI 1.5-9.1)). Children with confirmed or presumed COVID-19 have an increased risk of hypoxaemia during airway management in conjunction with general anaesthesia.

The efficacy of GlideScope® videolaryngoscopy compared with direct laryngoscopy in children who are difficult to intubate: an analysis from the paediatric difficult intubation registry.

BACKGROUND: We analysed data from the Paediatric Difficult Intubation Registry examining the use of direct laryngoscopy and GlideScope® videolaryngoscopy. METHODS: Data collected by a multicentre, paediatric difficult intubation registry from 1295 patients were analysed. Rates of success and complications between direct laryngoscopy and GlideScope videolaryngoscopy were analysed. RESULTS: Initial (464/877 = 53% vs 33/828 = 4%, Z-test = 22.2, P < 0.001) and eventual (720/877 = 82% vs. 174/828 = 21%, Z-test = 25.2, P < 0.001) success rates for GlideScope were significantly higher than direct laryngoscopy. Children weighing <10 kg had lower success rates with the GlideScope than the group as a whole. There were no differences in complication rates per attempt between direct laryngoscopy and GlideScope. The direct laryngoscopy group had more complications associated with the greater number of attempts needed to intubate. There were no increased risks of hypoxia or trauma with GlideScope use. Each additional attempt at intubation with either device resulted in a two-fold increase in complications (odds ratio: 2.0, 95% confidence interval: 1.5-2.5, P < 0.001). CONCLUSIONS: During difficult tracheal intubation in children, direct laryngoscopy is an overly used technique with a low chance of success. GlideScope use was associated with a higher chance of success with no increased risk of complications. GlideScope use in children with difficult tracheal intubation has a lower success rate than in adults with difficult tracheal intubation. Children weighing less than 10 kilograms had lower success rates with either device. Attempts should be minimized with either device to decrease complications.

Aminocaproic acid administration is associated with reduced perioperative blood loss and transfusion in pediatric craniofacial surgery.

BACKGROUND: Severe blood loss is a common complication of craniofacial reconstruction surgery. The antifibrinolytic ε-aminocaproic acid (EACA) reduces transfusion requirements in children undergoing cardiac surgery and in older children undergoing spine surgery. Tranexamic acid (TXA), another antifibrinolytic with a similar mechanism of action, has been shown to reduce blood loss and transfusion requirements in children undergoing craniofacial surgery. However, TXA has been associated with an increase in post-operative seizures and is more expensive than EACA. There is currently little published data evaluating the efficacy of EACA in children undergoing craniofacial surgery. METHODS: This is a retrospective study of prospectively collected data from our craniofacial perioperative registries for children under 6 years of age who underwent anterior or posterior cranial vault reconstruction. We compared calculated blood loss, blood donor exposures, and post-operative drain output between subjects who received EACA and those who did not. RESULTS: The registry queries returned data from 152 subjects. Eighty-six did not receive EACA and 66 received EACA. The EACA group had significantly lower calculated blood loss (82 ± 43 vs. 106 ± 63 ml/kg, P = 0.01), fewer intraoperative blood donor exposures (median 2, interquartile range 1-2 vs. median 2, interquartile range 1-3; P = 0.02) and lower surgical drain output in the first post-operative 24 h (28 ml/kg vs. 37 ml/kg, P = 0.001) than the non-EACA group. CONCLUSION: In this analysis of prospectively captured observational data, EACA administration was associated with less calculated blood loss, intraoperative blood donor exposures, and post-operative surgical drain output.

Population pharmacokinetics of ϵ-aminocaproic acid in adolescents undergoing posterior spinal fusion surgery.

BACKGROUND: Despite demonstrated efficacy of ϵ-aminocaproic acid (EACA) in reducing blood loss in adolescents undergoing spinal fusion, there are no population-specific pharmacokinetic data to guide dosing. The aim of this study was to determine the pharmacokinetics of EACA in adolescents undergoing spinal fusion surgery and make dosing recommendations. METHODS: Twenty children ages 12-17 years were enrolled, with 10 children in each of two groups based on diagnosis (idiopathic scoliosis or non-idiopathic scoliosis). Previously reported data from infants undergoing craniofacial surgery were included in the model to enable dosing recommendations over a wide range of weights, ages, and diagnoses. A population non-linear mixed effects modelling approach was used to characterize EACA pharmacokinetics. RESULTS: Population pharmacokinetic parameters were estimated using a two-compartment disposition model with allometrically scaled weight and an age effect on clearance. Pharmacokinetic parameters for the typical patient were a plasma clearance of 153 ml min(-1) 70 kg(-1) (6.32 ml min(-1) kg(-0.75)), intercompartmental clearance of 200 ml min(-1) 70 kg(-1) (8.26 ml min(-1) kg(-0.75)), central volume of distribution of 8.78 litre 70 kg(-1) (0.13 litre kg(-1)), and peripheral volume of distribution of 15.8 litre 70 kg(-1) (0.23 litre kg(-1)). Scoliosis aetiology did not have a clinically significant effect on drug pharmacokinetics. CONCLUSIONS: The following dosing schemes are recommended according to patient weight: weight <25 kg, 100 mg kg(-1) loading dose and 40 mg kg(-1) h(-1) infusion; weight ≤25 kg-<50 kg, 100 mg kg(-1) loading dose and 35 mg kg(-1) h(-1) infusion; and weight ≥50 kg, 100 mg kg(-1) loading dose and 30 mg kg(-1) h(-1) infusion. An efficacy trial employing this dosing strategy is warranted. CLINICAL TRIAL REGISTRATION: NCT01408823.

Videolaryngoscopes in pediatric anesthesia: what's new?

Anesthesiologists are increasingly turning to videolaryngoscopes (VLs) for normal and difficult endotracheal intubations. As children grow the airway is in constant transition. This means that a device that works well in an older child may fail in an infant. Are VLs ideal in all children? What are the pitfalls and strengths of these devices? When are they indicated? How should their efficacy be assessed? Can they play a role in teaching standard laryngoscopy? This article explores these questions and reviews the literature relating to VLs use in children.

Population pharmacokinetics of epsilon-aminocaproic acid in infants undergoing craniofacial reconstruction surgery.

BACKGROUND: Understanding the clinical pharmacology of the antifibrinolytic epsilon-aminocaproic acid (EACA) is necessary for rational drug administration in children. The aim of this study is to determine the pharmacokinetics (PKs) of EACA in infants aged 6-24 months undergoing craniofacial reconstruction surgery. METHODS: Cohorts of six infants were enrolled sequentially to one of the three escalating loading dose-continuous i.v. infusion (CIVI) regimens: 25 mg kg(-1), 10 mg kg(-1) h(-1); 50 mg kg(-1), 20 mg kg(-1) h(-1); 100 mg kg(-1), 40 mg kg(-1) h(-1). Plasma EACA concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry assay. A population non-linear mixed effects modelling approach was used to characterize EACA PKs. RESULTS: Population PK parameters of EACA were estimated using a two-compartment disposition model with weight expressed as an allometric covariate and an age effect. The typical patient in this study had an age of 38.71 weeks and a weight of 8.82 kg. PK parameters for this typical patient were: pre-/postoperative plasma drug clearance of 32 ml min(-1) (3.6 ml kg(-1) min(-1)), inter-compartmental clearance of 42.4 ml min(-1) (4.8 ml min(-1) kg(-1)), central volume of distribution of 1.27 litre (0.14 litre kg(-1)), and peripheral volume of distribution of 2.53 litre (0.29 litre kg(-1)). Intra-operative clearance and central volume of distribution were 89% and 80% of the pre-/postoperative value, respectively. CONCLUSIONS: EACA clearance increased with weight and age. The dependence of clearance on body weight supports weight-based dosing. Based on this study, a loading dose of 100 mg kg(-1) followed by a CIVI of 40 mg kg(-1) h(-1) is appropriate to maintain target plasma EACA concentrations in children aged 6-24 months undergoing these procedures.

Clusterin as a possible predictor for biochemical recurrence of prostate cancer following radical prostatectomy with intermediate Gleason scores: a preliminary report.

Disease recurrence following radical prostatectomy is a major concern in prostate cancer patients. Gleason scores are useful in predicting recurrence. Low Gleason scores are usually associated with long disease-free intervals, while high Gleason scores are suggestive of early recurrence. However, prediction of recurrence has been difficult with intermediate Gleason scores. Clusterin is a ubiquitous secretory sulfated glycoprotein. It is also an antiapoptotic mediator in prostate cancer. The objective of the present study is to determine if clusterin can serve as a predictive biomarker for recurrence of prostate cancer with intermediate Gleason scores in patients following radical prostatectomy. Prostatic specimens with Gleason score of 6 (3+3) or 7 (3+4) were obtained from the archival bank. Three groups of specimens were investigated. The first group was from nine patients who developed recurrent disease according to a persistent rise of serum PSA within 3 years following radical prostatectomy. Those in the second group and the third group were from patients who showed no evidence of disease recurrence for at least 5 y (11 patients) and 10 y (eight patients), respectively following the surgery. Histological sections were subjected to immunohistochemical staining using a monoclonal antibody specific for clusterin. The staining intensity was scored as 0, 1, 2, and 3, with 0 being no staining, 1 showing less than 25% positive staining, 2 being 25-50% positive, and 3 showing greater than 75% positive staining. One-way ANOVA with Bonferroni correction was used for statistical analysis. Evaluation of the scores of clusterin staining was carried out according to four specific areas in each specimen. They were (a) benign epithelial cells, (b) malignant epithelial cells (cancer epithelia), (c) stromal cells surrounding benign cells, and (d) stromal cells surrounding malignant cells (cancer stroma). Staining score in prostatic epithelial cells, benign as well as malignant, showed no significant relationship among the three patient groups. However, when staining scores in stromal cells were compared, there was a significant difference between patients with recurrent disease and those showed no evidence of disease recurrence for at least 10 y. Results of this preliminary study support the important role of clusterin in the stromal component for prostate cancer progression. Clusterin immunostaining may be useful to aid the prediction of chance of disease recurrence in patients with Gleason score 6 or 7 prostate cancer following radical prostatectomy. Further studies with a large number of cases are warranted to verify this preliminary finding.