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How big data shape paediatric anaesthesia

2017; Elsevier BV; Volume: 119; Issue: 3 Linguagem: Inglês

10.1093/bja/aex158

1471-6771

Jurgen C. de Graaff, Thomas Engelhardt,

Anesthesia and Sedative Agents

Paediatric anaesthesia practise is changing. This change is primarily the result of new evidence emerging from analyses of large datasets and represents a shift in focus from prevention of perioperative mortality towards a reduction of perioperative morbidity. Children do offer the unique opportunity to study the lifelong consequences of any early intervention. The effects of early-life surgical and anaesthetic exposure may resonate through adolescence and into adulthood. Therefore, it appears necessary to perform long-term follow-up over several years until higher cognitive and other physiological functions have been fully matured and developed. This concept of potential long-term impact of surgery and anaesthesia has come to the forefront over the past 15 years with an explosion of interest and academically lucrative research activity into numerous aspects of neurodevelopment. Experimental research of the effects of anaesthesia on long-term neurodevelopment has become a focus for research, resulting in >1000 scientific papers and consensus statements.1Jevtovic-Todorovic V Absalom AR Blomgren K et al.Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar.Br J Anaesth. 2013; 111: 143-151Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar Meanwhile, the potential neurotoxicity of anaesthetic agents on structural and functional brain development in humans has gained public notoriety. However, this is not consistent with clinical experience, most epidemiological studies, and prospective clinical trials.2Hansen TG Lonnqvist PA The rise and fall of anaesthesia-related neurotoxicity and the immature developing human brain.Acta Anaesthesiol Scand. 2016; 60: 280-283Crossref PubMed Scopus (14) Google Scholar 3O'Leary JD Warner DO What do recent human studies tell us about association between anaesthesia in young children and neurodevelopmental outcomes?.Br J Anaesth. 2017; 119: 524-531PubMed Google Scholar Recently, a truly long-term, robust large-scale database analysis of a Swedish nationwide cohort study comprising > 2 million children reported only a minimal effect of surgery in the first 4 years of life on subsequent academic performance. Gender, age at school entry, and maternal education are reported to have a far greater impact than the effect of surgery and anaesthesia.4Glatz P Sandin RH Pedersen NL Bonamy AK Eriksson LI Granath F Association of anesthesia and surgery during childhood with long-term academic performance.JAMA Pediatr. 2017; 171: e163470Crossref PubMed Scopus (190) Google Scholar This reassuring message has been confirmed by two other large nationwide cohort studies.5Graham MR Brownell M Chateau DG Dragan RD Burchill C Fransoo RR Neurodevelopmental assessment in kindergarten in children exposed to general anesthesia before the age of 4 years: a retrospective matched cohort study.Anesthesiology. 2016; 125: 667-677Crossref PubMed Scopus (118) Google Scholar 6O'Leary JD Janus M Duku E et al.A population-based study evaluating the association between surgery in early life and child development at primary school entry.Anesthesiology. 2016; 125: 272-279Crossref PubMed Scopus (108) Google Scholar The results of the interim analyses of the prospective randomized clinical trial General Anaesthesia versus Spinal (GAS) and the ambidirectional prospective cohort sibling study [Pediatric Anesthesia and Neurodevelopment Assessment (PANDA)] have further reassured clinicians of the safety of general anaesthesia in the very young.7Davidson AJ Disma N de Graaff JC et al.Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial.Lancet. 2016; 387: 239-250Abstract Full Text Full Text PDF PubMed Scopus (600) Google Scholar 8Sun LS Li G Miller TL et al.Association between a single general anesthesia exposure before age 36 months and neurocognitive outcomes in later childhood.JAMA. 2016; 315: 2312-2320Crossref PubMed Scopus (537) Google Scholar A major positive 'side effect' of this public interest in potential anaesthetic agent neurotoxicity is the increased scrutiny of the perioperative period and organisational setup. There is increased awareness that anaesthesia and surgery in young children may not always be absolutely necessary and beneficial to the health of the child. Consequently, a wider range of aspects of surgery and anaesthesia, such as physical, physiological, and psychological harm, are more openly considered by medical staff, parents, and children and the already known dangers of the perioperative period that result in measurable and preventable morbidity are acknowledged. These issues have now become subject to large (paediatric) database analyses and national audits.9Peden CJ Moonesinghe SR Measurement for improvement in anaesthesia and intensive care.Br J Anaesth. 2016; 117: 145-148Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar 10Moppett IK Moonesinghe SR Grocott MP National audits in the UK: fancy acronyms or real patient benefit?.Br J Anaesth. 2017; 118: 479-482Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar It is well established that anaesthesia in neonates and infants is associated with an increased risk of morbidity and mortality.11Ramamoorthy C Haberkern CM Bhananker SM et al.Anesthesia-related cardiac arrest in children with heart disease: data from the Pediatric Perioperative Cardiac Arrest (POCA) registry.Anesth Analg. 2010; 110: 1376-1382Crossref PubMed Scopus (237) Google Scholar 12Habre W Disma N Virag K et al.Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe.Lancet Respir Med. 2017; 5: 412-425Abstract Full Text Full Text PDF PubMed Scopus (363) Google Scholar The younger and smaller the patient, the greater the risk. Underlying pathology such as congenital heart disease, the urgency of the procedure, and hospital settings contribute further to morbidity and mortality.13Faraoni D Vo D Nasr VG DiNardo JA Development and validation of a risk stratification score for children with congenital heart disease undergoing noncardiac surgery.Anesth Analg. 2016; 123: 824-830Crossref PubMed Scopus (37) Google Scholar 14Harrison TE Engelhardt T MacFarlane F Flick RP Regionalization of pediatric anesthesia care: has the time come?.Paediatr Anaesth. 2014; 24: 897-898Crossref PubMed Scopus (7) Google Scholar Several key clinical factors responsible for this discrepancy in outcome are already known and prevention of these factors is considered the standard of care.15Weiss M Vutskits L Hansen TG Engelhardt T Safe anesthesia for every tot—the SAFETOTS initiative.Curr Opin Anaesthesiol. 2015; 28: 302-307Crossref PubMed Scopus (83) Google Scholar The reported overall anaesthesia and surgery-related mortality in older children approaches zero in some centres (1 in 10 000 in children <18 years of age) but remains 5 in 10 000 in neonates and infants.12Habre W Disma N Virag K et al.Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe.Lancet Respir Med. 2017; 5: 412-425Abstract Full Text Full Text PDF PubMed Scopus (363) Google Scholar 16de Bruin L Pasma W van der Werff DB et al.Perioperative hospital mortality at a tertiary paediatric institution.Br J Anaesth. 2015; 115: 608-615Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar 17van der Griend BF Lister NA McKenzie IM et al.Postoperative mortality in children after 101,885 anesthetics at a tertiary pediatric hospital.Anesth Analg. 2011; 112: 1440-1447Crossref PubMed Scopus (167) Google Scholar These figures originate from highly specialized centres with paediatric anaesthetic expertise, whereas the large majority of relatively healthy children are anaesthetized in non-specialized hospitals or non-paediatric settings. No comprehensive and detailed figures have yet been released to describe this practice or existing morbidity. Perioperative critical incidents in children are mostly airway related, such as laryngospasm, bronchospasm, hypoxaemia, and hypoventilation, and occur in almost 4% of anaesthetized children <1 year of age.18de Graaff JC Sarfo MC van WL van der Werff DB Schouten AN Anesthesia-related critical incidents in the perioperative period in children; a proposal for an anesthesia-related reporting system for critical incidents in children.Paediatr Anaesth. 2015; 25: 621-629Crossref PubMed Scopus (46) Google Scholar This is in contrast to adults where the most commonly reported critical incidents in the perioperative period affect the cardiovascular system with hypotension, arrhythmias, or cardiac arrest.19Munting KE van Zaane B Schouten AN van Wolfswinkel L de Graaff JC Reporting critical incidents in a tertiary hospital: a historical cohort study of 110,310 procedures.Can J Anaesth. 2015; 62: 1248-1258Crossref PubMed Scopus (17) Google Scholar As a direct consequence, proficiency in airway management is the cornerstone of safe paediatric anaesthesia practice. Suitable paediatric airway equipment is now also available.20Weiss M Dullenkopf A Fischer JE Keller C Gerber AC European Paediatric Endotracheal Intubation Study Group Prospective randomized controlled multi-centre trial of cuffed or uncuffed endotracheal tubes in small children.Br J Anaesth. 2009; 103: 867-873Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar However, neonates and children 30 years ago.23Anand KJ Sippell WG Aynsley-Green A Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response.Lancet. 1987; 1: 243-248Abstract PubMed Scopus (369) Google Scholar Recently, a number of dogmas in perioperative management have become subject to large RCTs. The results of these studies have radically changed clinical practice in the perioperative management of children. Traditionally, all patients were instructed to use the 'nil by mouth' policy, which frequently resulted in extensive starvation and severe dehydration with an increased risk of postoperative nausea and vomiting. Avoidance of dehydration through liberal fluid intake until transfer to the operating theatre may become the norm not only in children, but in adults as well.24Andersson H Zaren B Frykholm P Low incidence of pulmonary aspiration in children allowed intake of clear fluids until called to the operating suite.Paediatr Anaesth. 2015; 25: 770-777Crossref PubMed Scopus (94) Google Scholar 25Thomas M Engelhardt T Think drink! Current fasting guidelines are outdated.Br J Anaesth. 2017; 118: 291-293Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar Also, the lack of perioperative intake of glucose in children can result in severe hypoglycaemia in the postoperative period. In contrast, the use of glucose-containing isotonic solutions for perioperative care is not yet universally accepted.26McNab S Duke T South M et al.140 mmol/L of sodium versus 77 mmol/L of sodium in maintenance intravenous fluid therapy for children in hospital (PIMS): a randomised controlled double-blind trial.Lancet. 2015; 385: 1190-1197Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar 27Sumpelmann R Becke K Brenner S et al.Perioperative intravenous fluid therapy in children: guidelines from the Association of the Scientific Medical Societies in Germany.Paediatr Anaesth. 2017; 27: 10-18Crossref PubMed Scopus (61) Google Scholar Morbidity and mortality associated with perioperative hyponatraemia is an entirely avoidable complication. A recent large paediatric RCT demonstrated administration of isotonic fluid (sodium concentration of 140 mmol litre−1) reduced the risk of perioperative hyponatraemia.26McNab S Duke T South M et al.140 mmol/L of sodium versus 77 mmol/L of sodium in maintenance intravenous fluid therapy for children in hospital (PIMS): a randomised controlled double-blind trial.Lancet. 2015; 385: 1190-1197Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar Despite the availability of non-invasive blood pressure measurements in awake, healthy children, until recently no age- and gender-specific data during anaesthesia were available. Most recently, these data were generated from >110 000 primarily North American electronic anaesthesia records.28de Graaff JC Pasma W van Buuren S et al.Reference values for noninvasive blood pressure in children during anesthesia: a multicentered retrospective observational cohort study.Anesthesiology. 2016; 125: 904-913Crossref PubMed Scopus (70) Google Scholar These data will allow investigations of a potential correlation of intraoperative blood pressure variations and long-term morbidity and mortality.28de Graaff JC Pasma W van Buuren S et al.Reference values for noninvasive blood pressure in children during anesthesia: a multicentered retrospective observational cohort study.Anesthesiology. 2016; 125: 904-913Crossref PubMed Scopus (70) Google Scholar Other poorly documented areas such as medication errors and less appreciated perioperative factors may also be recognised. Most medication and drugs used in the perioperative period in children are off-label and appropriate pharmacokinetic and pharmacodynamic studies or long-term outcome studies have not been performed.29Oostenbrink R de Wildt SN Drug trials: kids are no little adults and not all kids are the same.J Clin Epidemiol. 2016; 71: 111-112Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar 30Allegaert K Sherwin C Neonates and medicines: a roadmap to further improve neonatal pharmaceutical care.Eur J Pediatr. 2016; 175: 743-746Crossref PubMed Scopus (4) Google Scholar 31Kaufmann J Wolf AR Becke K Laschat M Wappler F Engelhardt T Drug safety in paediatric anaesthesia.Br J Anaesth. 2017; 118: 670-679Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar Large-scale prospective observational studies and prospective paediatric clinical trials have been reported or finished recruitment. These studies provide an ever-increasing body of evidence that truly continues to shape this subspecialty. Of particular note are the two major prospective European initiatives—Anaesthesia Practice in Children Observational Trial (APRICOT) and the Neonate-Children Study of Anaesthesia Practice in Europe (NECTARINE)—that will provide baseline data for paediatric and neonatal anaesthesia practice in Europe.12Habre W Disma N Virag K et al.Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe.Lancet Respir Med. 2017; 5: 412-425Abstract Full Text Full Text PDF PubMed Scopus (363) Google Scholar 32Disma N Leva B Dowell J Veyckemans F Habre W Assessing anaesthesia practice in the vulnerable age group: NECTARINE. A European prospective multicentre observational study.Eur J Anaesthesiol. 2016; 33: 233-235Crossref PubMed Scopus (14) Google Scholar The APRICOT study consists of a large prospective collection of >30 000 comprehensive datasets of predefined perioperative critical complications across Europe. The NECTARINE study focuses on the population at highest risk and will identify variations in clinical practice in >5000 neonates. For the first time the effect of these factors will also be examined on 30- and 90-day outcomes. The major advantage is the nature of prospective data collection and the inclusion of both specialist and non-specialist settings. Ultimately, both studies may allow a direct comparison of anaesthetic practices in different hospital settings and regions, the effects of logistical setups, referral pathways and training, education in paediatric anaesthesia, and more political issues such as health care organisation and personal choices. These projects will have a direct and measurable effect on paediatric anaesthesia-related morbidity and mortality. Not all big data are the same, however. Data derived from traditional paper charts have numerous shortcomings, as they are typically incomplete, difficult to read, untraceable, and have limited accuracy in stressful situations. In addition, these data are not easily accessible for large-scale research. Electronic patient records (EPRs) have become standard practice in several large institutions in Europe and North America. Indeed, 75% of US academic anaesthesia departments now have EPR systems. Several hospital information technology systems are in existence, each with its own advantages and shortcomings depending on the level of data integration.33Giambrone GP Hemmings HC Sturm M Fleischut PM Information technology innovation: the power and perils of big data.Br J Anaesth. 2015; 115: 339-342Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar 34Simpao AF Ahumada LM Rehman MA Big data and visual analysis in anaesthesia and health care.Br J Anaesth. 2015; 115: 350-356Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar Specialized systems such as AIMS and the Patient Data Management System are highly regarded for their usability and personal adaptability but lack interactive feedback with hospital EPRs. On the other hand, integrated hospital-wide EPRs provide a comprehensive summary of patient data but suffer from the inflexibility to adapt to changes in daily clinical practice.35Motamed C Bourgain JL Benefits and possible improvements of an anaesthesia information management system in a quality assurance programme.Br J Anaesth. 2014; 113: 885-886Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Clinical, administrative, financial, insurance, and national registries have been used as a valuable source of information for retrospective analyses. However, the validity of this research is dependent on the quality of data, which can include false data and artefacts. This is less relevant for clinical purposes, as artefacts can often be identified on scrutiny of the clinical course. However, it is occasionally difficult or impossible to differentiate between a true value or an artefact, casting doubts on the reliability of reported findings.36Kool NP van Waes JA Bijker JB et al.Artifacts in research data obtained from an anesthesia information and management system.Can J Anaesth. 2012; 59: 833-841Crossref PubMed Scopus (27) Google Scholar Errors with administrative data also occur because of misclassification in the International Classification of Diseases (9th and 10th revisions).37McIsaac DI Gershon A Wijeysundera D Bryson GL Badner N van Walraven C Identifying obstructive sleep apnea in administrative data: a study of diagnostic accuracy.Anesthesiology. 2015; 123: 253-263Crossref PubMed Scopus (69) Google Scholar Prospective predefined outcome data and relevant clinical parameters need to be compared with the actual clinical course. This is labour intensive, expensive, and frequently variable. Definitions of universally accepted standard endpoints are urgently needed in order to design continuous quality assurance (QA) and quality improvement (QI) projects.38Myles PS Grocott MP Boney O Moonesinghe SR Group CO S. Standardizing end points in perioperative trials: towards a core and extended outcome set.Br J Anaesth. 2016; 116: 586-589Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar QA/QI projects require the development of universal but locally adaptable protocols, guidelines, and recommendations for all but the most unusual clinical circumstances. The setup of prospective national and international paediatric anaesthesia safety registries appears the logical consequence and should concentrate on the most vulnerable populations, such as young children and neonates and children with significant comorbidities. These registries can be joined from across allied specialties in order to assess and improve overall long-term outcomes.10Moppett IK Moonesinghe SR Grocott MP National audits in the UK: fancy acronyms or real patient benefit?.Br J Anaesth. 2017; 118: 479-482Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar A major criticism of big data studies is the ultimate failure to translate the results into concrete changes in clinical practice. For example, from old studies we already know that repeated airway instrumentation attempts, especially in small children, increase airway-related morbidity and mortality, as confirmed again recently.22Fiadjoe JE Nishisaki A Jagannathan N et al.Airway management complications in children with difficult tracheal intubation from the Pediatric Difficult Intubation (PeDI) registry: a prospective cohort analysis.Lancet Respir Med. 2016; 4: 37-48Abstract Full Text Full Text PDF PubMed Scopus (225) Google Scholar The introduction and strict adherence to locally accepted standard operating procedures (SOPs) and departmental guidelines are essential for such crucial manoeuvres in order to minimize or avoid catastrophes. Subsequently, commitment to ongoing education, teaching and training to the best available evidence, must be recognized as the most important aspect of continuing progress in paediatric anaesthesia. The findings of the GAS, PANDA, and more recently the APRICOT study emphasize the need to provide good clinical care (by experienced practitioners) in an appropriate environment. There is a very small possibility that early exposure to anaesthetic drugs harms the human brain in development. However, the risk of actual harm due to poor perioperative care and neglect of physiological homeostasis is real and recognised. It is possible to move away from the currently practiced individual 'art of neonatal and paediatric anaesthesia' and put modern paediatric anaesthesia practise onto a sound foundation of evidence-based practice that is supported by analysis of big data projects. Paediatric anaesthesia practise is changing. It will be for the better. J.d.G. and T.E. contributed equally to this article. None. None.