Summary
Background/Aims
As little as 30 minutes of exposure to anesthetic and sedative agents may adversely affect the developing brain. Safe, humane management of critically ill infants requires the ...use of sedative agents, often for prolonged periods. We sought to identify two comparable groups of critical care patients who did or did not receive sedatives, with the aim of designing a long‐term neurodevelopment follow‐up study. This feasibility study aimed to determine if two comparable groups could be found.
Methods
Infants with respiratory diagnoses having noninvasive ventilation without sedation (Group C) or intubation and ventilation with sedation (Group S) were identified by chart review. Charts of patients fulfilling the above inclusion criteria were searched for exclusion criteria including neurological disease, extreme prematurity, congenital cardiac disease, and genetic anomalies. Data were extracted to score pediatric severity of illness scores (PRISM and PELOD) for each patient. These scores were then compared using the absolute scores and by risk strata.
Results
Group S included 33 patients and Group C had 39. The absolute PRISM and PELOD scores were different between groups. Comparing the groups in three risk strata (PRISM greater or less than 5 or 10), there were no significant differences between groups.
Conclusion
It is not possible to randomize infants to sedation or no sedation to investigate neurodevelopmental outcomes. This phase of the project aimed to determine the comparability of two groups of PICU patients. These findings indicate that these groups could be enrolled as exposed and control subjects in an outcomes study.
To determine the accuracy of arterial blood pressure monitoring using 1) direct arterial; 2) automated oscillometric; and 3) sphygmomanometer/Doppler ultrasound measurements in pediatric intensive ...care patients comparing methods 1) and 2) with 3), the gold standard used to define normal blood pressure.
Prospective observational study.
Pediatric intensive care unit of a tertiary care pediatric teaching hospital.
Forty children (birth to 17 yrs) admitted to the pediatric intensive care unit with various clinical conditions requiring a radial arterial catheter for continuous arterial blood pressure monitoring.
None.
Each subject had measurements taken every 6 hrs over a 24-hr period. Each set of measurements were: direct arterial blood pressure, indirect blood pressure using the Phillips automated oscillometric device, and indirect blood pressure using the sphygmomanometer and Doppler ultrasound. Analysis used the Bland-Altman plot followed by paired t testing to compare the three different methods. One hundred sixty triads of measurements were analyzed. There were no significant differences between the methods of blood pressure measurement when groups were analyzed based on age. When analyzed by age-specific normo-, hypo-, and hypertensive criteria, arterial blood pressure measurements agree closely with Doppler ultrasound readings, whereas systolic arterial blood pressure measurements were lower than indirect blood pressure using the Phillips automated oscillometric device readings in the hypotensive group (p < .001). In the hypertensive group, the systolic arterial blood pressure values were higher and indirect blood pressure using the Phillips automated oscillometric device readings lower (p < .001) than Doppler ultrasound (p = .03). There was no clinically significant difference between methods in the normotensive group. Diastolic blood pressure measurements were higher by arterial blood pressure in normotensive and hypertensive groups but no different in the hypotensive group.
Outside the normotensive range, the automated readings were higher during hypotension and lower during hypertension compared with the arterial and Doppler ultrasound methods. The arterial blood pressure was closer to the gold standard Doppler ultrasound blood pressure in all three blood pressure groups.
The GAS trial – Authors' reply Davidson, Andrew J; Disma, Nicola; de Graaff, Jurgen C ...
The Lancet (British edition),
04/2016, Letnik:
387, Številka:
10028
Journal Article
Recenzirano
Odprti dostop
Beverley Orser and colleagues correctly point out the limitations of our study, which were also highlighted in our discussion and the accompanying Comment. 2 We agree that a more extensive follow-up ...of the children aged 5 years is essential, that indeed is our primary outcome. We also agree with Markus Weiss and colleagues that there are many other factors besides possible anaesthetic neurotoxic effects that might influence the short-term and long-term outcome of anaesthesia and surgery in infants. More evidence is required for many aspects of perioperative care in infants.
Summary
Introduction
Randomized trials are important for generating high‐quality evidence, but are perceived as difficult to perform in the pediatric population. Thus far there has been poor ...characterization of the barriers to conducting trials involving children, and the variation in these barriers between countries remains undescribed. The General Anesthesia compared to Spinal anesthesia (GAS) trial, conducted in seven countries between 2007 and 2013, provides an opportunity to explore these issues.
Methods
We undertook a descriptive analysis to evaluate the reasons for variation in enrollment between countries in the GAS trial, looking specifically at the number of potential subjects screened, and the subsequent application of four exclusion criteria that were applied in a hierarchical order.
Results
A total of 4023 patients were screened by 28 centers in seven countries. Australia and the USA screened the most subjects, accounting for 84% of all potential trial participants. The percentage of subjects eliminated from the screened pool by each exclusion criterion varied between countries. Exclusion due to a predefined condition (H1) eliminated only 5% of potential subjects in Italy and the UK, but 37% in Canada. Exclusions due to a contraindication or a physician's refusal most impacted enrollment in Australia and the USA. The patient being “too large for spinal anesthesia” was the most commonly cited by anesthetists who refused to enroll a patient (64% of anesthetist refusals). The majority of surgeon refusals came from the USA, where surgeons preferred the patient to receive a general anesthetic. The percentage of approached parents refusing to consent ranged from a low of 3% in Italy to a high of 70% in the USA and Netherlands. The most frequently cited reason for parent refusal in all countries was a preference for general anesthesia (median: 43%, range: 32%‐67%). However, a sizeable proportion of parents in all countries had a contrasting preference for spinal anesthesia (median: 25%, range: 13%‐31%), and 23% of U.S. parents expressed concern about randomization.
Conclusion
The GAS trial highlights enrollment challenges that can occur when conducting multicenter, international, pediatric studies. Investigators planning future trials should be aware of potential differences in screening processes across countries, and that exclusions by anesthetists and surgeons may vary in reason, in frequency, and by country. Furthermore, investigators should be aware that the U.S. centers encountered particularly high surgeon and parental refusal rates and that U.S. parents were uniquely concerned about randomization. Planning trials that address these difficulties should increase the likelihood of successfully recruiting subjects in pediatric trials.
Summary Background Preclinical data suggest that general anaesthetics affect brain development. There is mixed evidence from cohort studies that young children exposed to anaesthesia can have an ...increased risk of poor neurodevelopmental outcome. We aimed to establish whether general anaesthesia in infancy has any effect on neurodevelopmental outcome. Here we report the secondary outcome of neurodevelopmental outcome at 2 years of age in the General Anaesthesia compared to Spinal anaesthesia (GAS) trial. Methods In this international assessor-masked randomised controlled equivalence trial, we recruited infants younger than 60 weeks postmenstrual age, born at greater than 26 weeks' gestation, and who had inguinal herniorrhaphy, from 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand. Infants were randomly assigned (1:1) to receive either awake-regional anaesthesia or sevoflurane-based general anaesthesia. Web-based randomisation was done in blocks of two or four and stratified by site and gestational age at birth. Infants were excluded if they had existing risk factors for neurological injury. The primary outcome of the trial will be the Wechsler Preschool and Primary Scale of Intelligence Third Edition (WPPSI-III) Full Scale Intelligence Quotient score at age 5 years. The secondary outcome, reported here, is the composite cognitive score of the Bayley Scales of Infant and Toddler Development III, assessed at 2 years. The analysis was as per protocol adjusted for gestational age at birth. A difference in means of five points (1/3 SD) was predefined as the clinical equivalence margin. This trial is registered with ANZCTR, number ACTRN12606000441516 and ClinicalTrials.gov , number NCT00756600. Findings Between Feb 9, 2007, and Jan 31, 2013, 363 infants were randomly assigned to receive awake-regional anaesthesia and 359 to general anaesthesia. Outcome data were available for 238 children in the awake-regional group and 294 in the general anaesthesia group. In the as-per-protocol analysis, the cognitive composite score (mean SD) was 98·6 (14·2) in the awake-regional group and 98·2 (14·7) in the general anaesthesia group. There was equivalence in mean between groups (awake-regional minus general anaesthesia 0·169, 95% CI −2·30 to 2·64). The median duration of anaesthesia in the general anaesthesia group was 54 min. Interpretation For this secondary outcome, we found no evidence that just less than 1 h of sevoflurane anaesthesia in infancy increases the risk of adverse neurodevelopmental outcome at 2 years of age compared with awake-regional anaesthesia. Funding Australia National Health and Medical Research Council (NHMRC), Health Technologies Assessment-National Institute for Health Research UK, National Institutes of Health, Food and Drug Administration, Australian and New Zealand College of Anaesthetists, Murdoch Childrens Research Institute, Canadian Institute of Health Research, Canadian Anesthesiologists' Society, Pfizer Canada, Italian Ministry of Heath, Fonds NutsOhra, and UK Clinical Research Network (UKCRN).
Inhaled volatile anesthetics support management of status asthmaticus (SA), status epilepticus (SE), and difficult sedation (DS). This study aimed to evaluate the effectiveness, safety, and ...feasibility of using inhaled anesthetics for SA, SE, and DS in adult ICU and PICU patients.
MEDLINE, Cochrane Central Register of Controlled Trials, and Embase.
Primary literature search that reported the use of inhaled anesthetics in ventilated patients with SA, SE, and DS from 1970 to 2021.
Study data points were extracted by two authors independently. Quality assessment was performed using the Joanna Briggs Institute appraisal tool for case studies/series, Newcastle criteria for cohort/case-control studies, and risk-of-bias framework for clinical trials.
Primary outcome was volatile efficacy in improving predefined clinical or physiologic endpoints. Secondary outcomes were adverse events and delivery logistics. From 4281 screened studies, the number of included studies/patients across diagnoses and patient groups were: SA (adult: 38/121, pediatric: 28/142), SE (adult: 18/37, pediatric: 5/10), and DS (adult: 21/355, pediatric: 10/90). Quality of evidence was low, consisting mainly of case reports and series. Clinical and physiologic improvement was seen within 1-2 hours of initiating volatiles, with variable efficacy across diagnoses and patient groups: SA (adult: 89-95%, pediatric: 80-97%), SE (adults: 54-100%, pediatric: 60-100%), and DS (adults: 60-90%, pediatric: 62-90%). Most common adverse events were cardiovascular, that is, hypotension and arrhythmias. Inhaled sedatives were commonly delivered using anesthesia machines for SA/SE and miniature vaporizers for DS. Few (10%) of studies reported required non-ICU personnel, and only 16% had ICU volatile delivery protocol.
Volatile anesthetics may provide effective treatment in patients with SA, SE, and DS scenarios but the quality of evidence is low. Higher-quality powered prospective studies of the efficacy and safety of using volatile anesthetics to manage SA, SE, and DS patients are required. Education regarding inhaled anesthetics and the protocolization of their use is needed.
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