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Papers by Tom Hansen
Current opinion in anaesthesiology, 2018
Repeated controversial and alarming statements of the potential dangers of anaesthetic agents on ... more Repeated controversial and alarming statements of the potential dangers of anaesthetic agents on neurological outcomes in children continue to be issued based primarily on preclinical studies. This review assesses the current evidence of laboratory and clinical data and identifies areas of concerns. Published animal and laboratory data consistently indicate that prolonged and excessive use of anaesthetic agents can lead to morphological changes and neurocognitive impairment in animals without a clear cut-off age or a superiority of one technique over another. Retrospective human studies and prospective clinical trials indicate that short exposures to anaesthesia and surgery are safe and have no effect on long-term neurological outcomes. Small and consistent continuing improvements in the perioperative period (aggregation of marginal gains) will impact on long-term neurological morbidity in humans. It is biologically plausible that anaesthetic agents may induce structural changes dur...
Current opinion in anaesthesiology, 2018
DOI:10.1097/ACO.0000000000000596 The interests in research and outcome in children exposed to ana... more DOI:10.1097/ACO.0000000000000596 The interests in research and outcome in children exposed to anaesthesia and surgery has increased dramatically the past 10–15 years as a consequence of the increasing volume of preclinical studies demonstrating that general anaesthetics are neurotoxic to the immature animal brain. This paediatric issue of Current Opinion in Anaesthesiology contains nine interesting review articles by some of the leading scientific paediatric anaesthesiologist underlining this fact. The first article is by Walid Habre from Geneva, Switzerland. He is the lead investigator of the APRICOT study which was published in the Lancet Respiratory Medicine in May 2017 [1]. In his review article (pp. 292–296), he interprets the results of the APRICOT study and highlights the requirements for harmonization of training, certification and continuous professional development and discusses the implications for anaesthesia management of children in Europe. In the second article (pp. 297–301), Tom G. Hansen from Odense, Denmark and Thomas Engelhardt from Aberdeen, Scotland provide an update on the human studies regarding neurocognitive outcomes following anaesthesia and surgical exposures in early life. They argue that it may well be biologically plausible that anaesthetic agents induce structural changes during mammalian brain development and beyond. However, in the absence of alternatives, the impact of the choice of anaesthetic drugs on long-term neurocognitive outcomes is almost certainly to be of limited relevance in humans. The underlying disease processes, surgical intervention and trauma as well as other known perioperative factors affect these outcomes more significantly. As a spin-off from the GAS study [2] – the only randomized controlled trial on this topic so far – a number of additional studies have been published, for example regarding to the safety and efficacy of regional anaesthesia in infants. Some of these studies are summarized (pp. 302–307) by Nicola Disma and Natasha Lunies-Ross from London, United Kingdom and George A. Chalkiakis from Melbourne, Australia. They conclude that spinal
Acta Anaesthesiologica Scandinavica
Archives of disease in childhood. Education and practice edition, Oct 11, 2017
This is a repository copy of General anaesthesia under the age of 4 years has minimal impact on f... more This is a repository copy of General anaesthesia under the age of 4 years has minimal impact on future academic performance.
European journal of anaesthesiology, Jun 1, 2017
Furthermore, the implied 'safe' cutoff points of age 3 years or duration of procedure of 3 h quot... more Furthermore, the implied 'safe' cutoff points of age 3 years or duration of procedure of 3 h quoted in the FDA warning statement are not currently supported by evidence derived from human studies.
Paediatric anaesthesia, Jun 1, 2017
The Lancet. Respiratory medicine, May 28, 2017
Little is known about the incidence of severe critical events in children undergoing general anae... more Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered w...
JAMA pediatrics, Jan 2, 2017
Preclinical studies 1-3 in young animals have demonstrated neurodegeneration and subsequent neuro... more Preclinical studies 1-3 in young animals have demonstrated neurodegeneration and subsequent neurocognitive impairment for virtually all clinically available general anesthetic drugs. However, comparative human studies on this issue are scarce and inconclusive. Several reasons account for this discrepancy. First, preclinical animal studies were never driven by a clinical suspicion of neurocognitive deficits associated with exposure to anesthetic drugs in early life. There is no welldefined and specific longterm phenotype associated with exposure to anesthetic drugs. The first preclinical investigations were extrapolated from findings related to fetal alcohol syndrome and long-term fetal exposure to antiepileptic drugs. 3 An a priori expectation that anesthetic drugs also would be neurodegenerative in comparable experimental settings was based on the putative (but unknown) mechanisms of actions of anesthetics. 3 A large number of studies, reviews, and commentaries have since been published as a result. 4,5 There are many challenges that need to be overcome when translating animal studies into a human context. 3,6 If exposure to anesthetic drugs was indeed as harmful in early human life as hypothesized, 4,5 this effect would most likely have been suspected many years ago. Some observational cohort studies 7-9 have demonstrated an association between negative long-term neurocognitive outcomes in young children exposed to anesthesia (and surgery), perpetuating any anxiety. Most of these observational investigations are from single centers (prone to selection bias) reporting on small sample sizes with large age ranges (and very few neonates and infants) and a multitude of surgical procedures. Inconsistent outcome measures confuse the public and professionals alike, resulting in a failure to demonstrate a human corollary to this animal phenomenon. However, what constitutes a meaningful human outcome measure? What is important for the child, the parent, and the public interest? The most commonly reported neurocognitive outcome measures in humans are IQ, learning disabilities, academic performance, neuropsychiatric disorders (autism and attentiondeficit/hyperactivity disorder), and individual neuropsychological test results (eg, Bayley and Wechsler scores). 3 All of these outcome measures have limitations. A global neurocognitive decline (affecting IQ, learning disabilities, and attention-deficit/ hyperactivity disorder) may be the consequence of an indiscriminate effect of anesthetic drugs. If specific brain areas are damaged during susceptible developmental times, the relevant neurological outcome may be subtle (eg, reading, speak
Lancet (London, England), Jan 16, 2016
Ambulatory Anesthesia, 2015
Animal studies (including in nonhuman primates) have shown that most general anesthetics cause en... more Animal studies (including in nonhuman primates) have shown that most general anesthetics cause enhanced neuroapoptosis in the immature brain with subsequent long-term neurocognitive deficits later in life. Whether human neurons are equally affected is yet unknown, but a final answer to this issue is still pending. To date, most human studies within the field are of observational nature and the results are conflicting. Some studies indicate an association between exposure to anesthesia and surgery while others do not. Objective: This review summarizes results from preclinical and observational studies. Controversies and challenges regarding the interpretation of these results are presented. Crucial aspects of neurocognitive safety during pediatric anesthesia and surgery are highlighted. International initiatives aiming to improve the safe conductance of pediatric anesthesia are introduced. Conclusion: So far, anesthesia-related neurotoxicity in humans remains an area of concern but it cannot be completely excluded. Clinical practice should not be changed until there are definite proofs that anesthetic exposure causes neurocognitive impairment later in life. Withholding necessary and timely surgeries as a consequence of any such concerns could result in worse harm. Focus of current research should also be redirected to include other factors, than merely anesthetics and surgery, that influence the neurocognitive safety of children perioperatively.
Current opinion in anaesthesiology, 2015
There is a growing medical demand for suitable sedatives and analgesics to support the ongoing pr... more There is a growing medical demand for suitable sedatives and analgesics to support the ongoing progress in diagnostic procedures and imaging techniques. This review provides an update of the pharmacology of the most commonly used drugs used for these procedures and shortly mention new drugs on the horizon. There are many drugs available for procedural sedation; however, they all have drawbacks and shortcomings. Multiple adverse effects are associated with the use of these agents, hence monitoring is essential, and emergency equipment should be readily available.Newer drugs are on the horizon (e.g., remimazolam, fospropofol, and etomidate analogues) with a theoretical more predictable onset and offset; whether these will revolutionize the sedational practice sedation remains unknown. Clinicians should be aware of the pharmacokinetic/pharmacodynamic differences of all agents in order to select appropriate medications for specific procedures and patients.
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, Jan 24, 2015
Experimental evidence indicates that general anaesthetics can induce apoptotic neurodegeneration ... more Experimental evidence indicates that general anaesthetics can induce apoptotic neurodegeneration in the developing brain. The majority of these studies have been performed in the absence of surgery and it currently remains unclear how the presence of surgical stimuli would influence neuroapoptosis as well as systemic homeostasis. Here we explored this possibility by performing dorsal skin flap surgery in young and adult rats under four distinct currently used anaesthesia regimens. Young (21-days) and adult (2 months) male Sprague-Dawley rats were randomized to 150min exposure to one of four anaesthetics regimens: (i) sevoflurane/dexmedetomidine, (ii) sevoflurane/fentanyl; (iii) propofol/dexmedetomidine, and (iv) propofol/fentanyl. Animals underwent a dorsal skin flap procedure while physiologic, metabolic and biochemical parameters were closely monitored. Neuroapoptotic profiles were evaluated in the cortex, thalamus and hippocampus (CA1 and CA3) at the end of the procedure in each ...
Current Opinion in Anaesthesiology, 2015
PURPOSE OF REVIEW The term 'safe use of anesthesia in children is ill-defined and requires defini... more PURPOSE OF REVIEW The term 'safe use of anesthesia in children is ill-defined and requires definition of and focus on the 'safe conduct of pediatric anesthesia'. RECENT FINDINGS The Safe Anesthesia For Every Tot initiative (www.safetots.org) has been set up during the last year to focus on the safe conduct of pediatric anesthesia. This initiative aims to provide guidance on markers of quality anesthesia care. The introduction and implementation of national regulations of 'who, where, when and how' are required and will result in an improved perioperative outcome in vulnerable children. The improvement of teaching, training, education and supervision of the safe conduct of pediatric anesthesia are the main goals of the safetots.org initiative. SUMMARY This initiative addresses the well known perioperative risks in young children, perioperative causes for cerebral morbidity as well as gaps in regulations, teaching and research. Defining the 'who', 'where', 'when' and 'how' in this context provides the framework for the safe conduct of pediatric anesthesia.
Paediatric anaesthesia, 2015
Few human cohort studies on anesthesia-related neurotoxicity and the developing brain have focuse... more Few human cohort studies on anesthesia-related neurotoxicity and the developing brain have focused on and compared specific surgeries and conditions. These studies cannot disentangle the effects of anesthesia from those of the surgery and underlying conditions. This study aimed at assessing the impact of specific neurosurgical conditions and procedures in infancy on mortality and academic achievements in adolescence. A nationwide unselected register-based follow-up study of the Danish birth cohorts 1986-1990 compared academic performances of all children having undergone neurosurgeries as infants with a randomly selected, age-matched 5% sample of the same cohorts. The two groups were compared regarding mortality prior to June 1st, 2006, average test scores at ninth grade, and finally the proportion of children not attaining test scores. The exposure group comprised 228 and the control group 14 698 individuals. Hydrocephalus (n = 130), craniotomy (n = 43), and myelomeningocele/enceph...
European journal of anaesthesiology, 2015
A popular advertising campaign in the 1980s and 1990s illustrated the dangers of drug and alcohol... more A popular advertising campaign in the 1980s and 1990s illustrated the dangers of drug and alcohol abuse for the teenage brain by showing a raw egg (‘This is your brain’) being cracked and fried in a pan (‘This is your brain on drugs’). In a sense, this was a simplified representation of the phenotype of drug use in the developing teenage brain (https://www.youtube.com/watch?v=ub_a2t0ZfTs; Accessed June 2014). Currently, researchers are trying to identify whether there exists a neurological phenotype following early childhood exposure to a class of therapeutic drugs, anaesthetics and sedatives. Concerns for potential harmful effects of anaesthetics on brain development in young children undergoing surgical procedures were first raised by animal studies demonstrating widespread cell death of neurones and oligodendrocytes, reductions in neurotrophic factors, alterations in synaptic and dendritic densities, disintegration of the cytoskeleton and long-term neurocognitive impairment following anaesthetic exposure early in life. Subsequently, epidemiological studies established an association between surgical exposure during the first 3 to 4 years of life with learning disabilities, behavioural and developmental
Paediatric anaesthesia, 2015
1 Hansen TG. Anesthesia-related neurotoxicity and the developing animal brain is not a significan... more 1 Hansen TG. Anesthesia-related neurotoxicity and the developing animal brain is not a significant problem in children. Pediatr Anesth 2014; 25: 65–72. 2 Hansen TG, Pedersen JK, Henneberg SW et al. Neurosurgical conditions and procedures in infancy are associated with mortality and academic performances in adolescence: a nationwide cohort study. Pediatr Anesth 2015; 25: 186–192. 3 Wilder RT, Flick RP, Sprung J et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology 2009; 110: 796–804. 4 Hansen TG, Flick R. Anesthetic effects on the developing brain: insights from epidemiology. Anesthesiology 2009; 110: 1–3. 5 Flick RP, Warner DO. A users’ guide to interpreting observational studies of pediatric anesthetic neurotoxicity: the lessons of Sir Bradford Hill. Anesthesiology 2012; 117: 459–462.
Ugeskrift for laeger, Jan 18, 2014
Animal studies (including non-human primates) have shown that most general anaesthetics cause enh... more Animal studies (including non-human primates) have shown that most general anaesthetics cause enhanced neuroapoptosis with subsequent long-term neurocognitive deficits later in life. Some human cohort studies have indicated an association between anaesthesia/surgery and adverse neurocognitive outcome whereas other studies have not. Overall, the data do not justify any change in paediatric anaesthetic clinical practice. Naturally, the risks and benefits of a procedure should always be carefully considered before exposing a child to general anaesthesia.
Paediatric anaesthesia, 2015
A multitude of animal studies have shown that virtually all general anesthetics used in clinical ... more A multitude of animal studies have shown that virtually all general anesthetics used in clinical practice possibly during a vulnerable period of brain development (i.e., brain growth spurt, peak of synaptogenesis) may lead to neurodegeneration (particularly apoptosis) and abnormal synaptic development with functional deficits in learning and behavior later in life. Initial studies were mainly performed in immature rodent pups, but more recent studies have included nonhumans primates (rhesus monkeys). Given the number of neonates, infants, and young children anesthetized annually worldwide, these findings could have significant public health implications. So far, relatively few human (cohort) studies focusing on this topic have been published with inconsistent results. While some studies have indicated an association between exposure to anesthesia and surgery, other studies have indicated no such association. Prospective studies are underway, but the result will not be available for ...
![Research paper thumbnail of [Paediatric intensive care in Denmark]](https://attachments.academia-assets.com/83869489/thumbnails/1.jpg)
](Ugeskrift for laeger, Jan 19, 2007
The practice of paediatric intensive care has matured dramatically over the past 20 years with im... more The practice of paediatric intensive care has matured dramatically over the past 20 years with improving intensive care unit mortality rates and a positive effect on child survival. This paper gives an overview of many of these aspects, and attempts to present a picture of the present situation in Denmark. Internationally, much of this progress has been carried out by means of a strong centralisation of the service, given its low volume, highly specialised and high cost nature. In Denmark, critically ill children are cared for in at least 27 primarily adult intensive care units by nurses and doctors who are not specifically trained in paediatric intensive care. Suggestions for a more centralisation of paediatric intensive care in Denmark are made.
Ugeskrift for laeger, Jan 26, 2005
Propofol infusion syndrome, characterised by cardiovascular collapse, metabolic acidosis, hepatom... more Propofol infusion syndrome, characterised by cardiovascular collapse, metabolic acidosis, hepatomegaly, renal failure and rhabdomyolysis, is a rare and often fatal syndrome seen in critically ill children undergoing long-term propofol sedation. Propofol may impair mitochondrial free fatty acid metabolism, resulting in an imbalance between energy demand and utilisation and thus compromising cardiac and peripheral muscle cell function. Propofol should be used with caution for sedation in critically ill children, as well as for long-term anaesthesia in otherwise healthy children, and doses exceeding 4 mg/kg/h should be avoided.
Current opinion in anaesthesiology, 2018
Repeated controversial and alarming statements of the potential dangers of anaesthetic agents on ... more Repeated controversial and alarming statements of the potential dangers of anaesthetic agents on neurological outcomes in children continue to be issued based primarily on preclinical studies. This review assesses the current evidence of laboratory and clinical data and identifies areas of concerns. Published animal and laboratory data consistently indicate that prolonged and excessive use of anaesthetic agents can lead to morphological changes and neurocognitive impairment in animals without a clear cut-off age or a superiority of one technique over another. Retrospective human studies and prospective clinical trials indicate that short exposures to anaesthesia and surgery are safe and have no effect on long-term neurological outcomes. Small and consistent continuing improvements in the perioperative period (aggregation of marginal gains) will impact on long-term neurological morbidity in humans. It is biologically plausible that anaesthetic agents may induce structural changes dur...
Current opinion in anaesthesiology, 2018
DOI:10.1097/ACO.0000000000000596 The interests in research and outcome in children exposed to ana... more DOI:10.1097/ACO.0000000000000596 The interests in research and outcome in children exposed to anaesthesia and surgery has increased dramatically the past 10–15 years as a consequence of the increasing volume of preclinical studies demonstrating that general anaesthetics are neurotoxic to the immature animal brain. This paediatric issue of Current Opinion in Anaesthesiology contains nine interesting review articles by some of the leading scientific paediatric anaesthesiologist underlining this fact. The first article is by Walid Habre from Geneva, Switzerland. He is the lead investigator of the APRICOT study which was published in the Lancet Respiratory Medicine in May 2017 [1]. In his review article (pp. 292–296), he interprets the results of the APRICOT study and highlights the requirements for harmonization of training, certification and continuous professional development and discusses the implications for anaesthesia management of children in Europe. In the second article (pp. 297–301), Tom G. Hansen from Odense, Denmark and Thomas Engelhardt from Aberdeen, Scotland provide an update on the human studies regarding neurocognitive outcomes following anaesthesia and surgical exposures in early life. They argue that it may well be biologically plausible that anaesthetic agents induce structural changes during mammalian brain development and beyond. However, in the absence of alternatives, the impact of the choice of anaesthetic drugs on long-term neurocognitive outcomes is almost certainly to be of limited relevance in humans. The underlying disease processes, surgical intervention and trauma as well as other known perioperative factors affect these outcomes more significantly. As a spin-off from the GAS study [2] – the only randomized controlled trial on this topic so far – a number of additional studies have been published, for example regarding to the safety and efficacy of regional anaesthesia in infants. Some of these studies are summarized (pp. 302–307) by Nicola Disma and Natasha Lunies-Ross from London, United Kingdom and George A. Chalkiakis from Melbourne, Australia. They conclude that spinal
Acta Anaesthesiologica Scandinavica
Archives of disease in childhood. Education and practice edition, Oct 11, 2017
This is a repository copy of General anaesthesia under the age of 4 years has minimal impact on f... more This is a repository copy of General anaesthesia under the age of 4 years has minimal impact on future academic performance.
European journal of anaesthesiology, Jun 1, 2017
Furthermore, the implied 'safe' cutoff points of age 3 years or duration of procedure of 3 h quot... more Furthermore, the implied 'safe' cutoff points of age 3 years or duration of procedure of 3 h quoted in the FDA warning statement are not currently supported by evidence derived from human studies.
Paediatric anaesthesia, Jun 1, 2017
The Lancet. Respiratory medicine, May 28, 2017
Little is known about the incidence of severe critical events in children undergoing general anae... more Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered w...
JAMA pediatrics, Jan 2, 2017
Preclinical studies 1-3 in young animals have demonstrated neurodegeneration and subsequent neuro... more Preclinical studies 1-3 in young animals have demonstrated neurodegeneration and subsequent neurocognitive impairment for virtually all clinically available general anesthetic drugs. However, comparative human studies on this issue are scarce and inconclusive. Several reasons account for this discrepancy. First, preclinical animal studies were never driven by a clinical suspicion of neurocognitive deficits associated with exposure to anesthetic drugs in early life. There is no welldefined and specific longterm phenotype associated with exposure to anesthetic drugs. The first preclinical investigations were extrapolated from findings related to fetal alcohol syndrome and long-term fetal exposure to antiepileptic drugs. 3 An a priori expectation that anesthetic drugs also would be neurodegenerative in comparable experimental settings was based on the putative (but unknown) mechanisms of actions of anesthetics. 3 A large number of studies, reviews, and commentaries have since been published as a result. 4,5 There are many challenges that need to be overcome when translating animal studies into a human context. 3,6 If exposure to anesthetic drugs was indeed as harmful in early human life as hypothesized, 4,5 this effect would most likely have been suspected many years ago. Some observational cohort studies 7-9 have demonstrated an association between negative long-term neurocognitive outcomes in young children exposed to anesthesia (and surgery), perpetuating any anxiety. Most of these observational investigations are from single centers (prone to selection bias) reporting on small sample sizes with large age ranges (and very few neonates and infants) and a multitude of surgical procedures. Inconsistent outcome measures confuse the public and professionals alike, resulting in a failure to demonstrate a human corollary to this animal phenomenon. However, what constitutes a meaningful human outcome measure? What is important for the child, the parent, and the public interest? The most commonly reported neurocognitive outcome measures in humans are IQ, learning disabilities, academic performance, neuropsychiatric disorders (autism and attentiondeficit/hyperactivity disorder), and individual neuropsychological test results (eg, Bayley and Wechsler scores). 3 All of these outcome measures have limitations. A global neurocognitive decline (affecting IQ, learning disabilities, and attention-deficit/ hyperactivity disorder) may be the consequence of an indiscriminate effect of anesthetic drugs. If specific brain areas are damaged during susceptible developmental times, the relevant neurological outcome may be subtle (eg, reading, speak
Lancet (London, England), Jan 16, 2016
Ambulatory Anesthesia, 2015
Animal studies (including in nonhuman primates) have shown that most general anesthetics cause en... more Animal studies (including in nonhuman primates) have shown that most general anesthetics cause enhanced neuroapoptosis in the immature brain with subsequent long-term neurocognitive deficits later in life. Whether human neurons are equally affected is yet unknown, but a final answer to this issue is still pending. To date, most human studies within the field are of observational nature and the results are conflicting. Some studies indicate an association between exposure to anesthesia and surgery while others do not. Objective: This review summarizes results from preclinical and observational studies. Controversies and challenges regarding the interpretation of these results are presented. Crucial aspects of neurocognitive safety during pediatric anesthesia and surgery are highlighted. International initiatives aiming to improve the safe conductance of pediatric anesthesia are introduced. Conclusion: So far, anesthesia-related neurotoxicity in humans remains an area of concern but it cannot be completely excluded. Clinical practice should not be changed until there are definite proofs that anesthetic exposure causes neurocognitive impairment later in life. Withholding necessary and timely surgeries as a consequence of any such concerns could result in worse harm. Focus of current research should also be redirected to include other factors, than merely anesthetics and surgery, that influence the neurocognitive safety of children perioperatively.
Current opinion in anaesthesiology, 2015
There is a growing medical demand for suitable sedatives and analgesics to support the ongoing pr... more There is a growing medical demand for suitable sedatives and analgesics to support the ongoing progress in diagnostic procedures and imaging techniques. This review provides an update of the pharmacology of the most commonly used drugs used for these procedures and shortly mention new drugs on the horizon. There are many drugs available for procedural sedation; however, they all have drawbacks and shortcomings. Multiple adverse effects are associated with the use of these agents, hence monitoring is essential, and emergency equipment should be readily available.Newer drugs are on the horizon (e.g., remimazolam, fospropofol, and etomidate analogues) with a theoretical more predictable onset and offset; whether these will revolutionize the sedational practice sedation remains unknown. Clinicians should be aware of the pharmacokinetic/pharmacodynamic differences of all agents in order to select appropriate medications for specific procedures and patients.
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, Jan 24, 2015
Experimental evidence indicates that general anaesthetics can induce apoptotic neurodegeneration ... more Experimental evidence indicates that general anaesthetics can induce apoptotic neurodegeneration in the developing brain. The majority of these studies have been performed in the absence of surgery and it currently remains unclear how the presence of surgical stimuli would influence neuroapoptosis as well as systemic homeostasis. Here we explored this possibility by performing dorsal skin flap surgery in young and adult rats under four distinct currently used anaesthesia regimens. Young (21-days) and adult (2 months) male Sprague-Dawley rats were randomized to 150min exposure to one of four anaesthetics regimens: (i) sevoflurane/dexmedetomidine, (ii) sevoflurane/fentanyl; (iii) propofol/dexmedetomidine, and (iv) propofol/fentanyl. Animals underwent a dorsal skin flap procedure while physiologic, metabolic and biochemical parameters were closely monitored. Neuroapoptotic profiles were evaluated in the cortex, thalamus and hippocampus (CA1 and CA3) at the end of the procedure in each ...
Current Opinion in Anaesthesiology, 2015
PURPOSE OF REVIEW The term 'safe use of anesthesia in children is ill-defined and requires defini... more PURPOSE OF REVIEW The term 'safe use of anesthesia in children is ill-defined and requires definition of and focus on the 'safe conduct of pediatric anesthesia'. RECENT FINDINGS The Safe Anesthesia For Every Tot initiative (www.safetots.org) has been set up during the last year to focus on the safe conduct of pediatric anesthesia. This initiative aims to provide guidance on markers of quality anesthesia care. The introduction and implementation of national regulations of 'who, where, when and how' are required and will result in an improved perioperative outcome in vulnerable children. The improvement of teaching, training, education and supervision of the safe conduct of pediatric anesthesia are the main goals of the safetots.org initiative. SUMMARY This initiative addresses the well known perioperative risks in young children, perioperative causes for cerebral morbidity as well as gaps in regulations, teaching and research. Defining the 'who', 'where', 'when' and 'how' in this context provides the framework for the safe conduct of pediatric anesthesia.
Paediatric anaesthesia, 2015
Few human cohort studies on anesthesia-related neurotoxicity and the developing brain have focuse... more Few human cohort studies on anesthesia-related neurotoxicity and the developing brain have focused on and compared specific surgeries and conditions. These studies cannot disentangle the effects of anesthesia from those of the surgery and underlying conditions. This study aimed at assessing the impact of specific neurosurgical conditions and procedures in infancy on mortality and academic achievements in adolescence. A nationwide unselected register-based follow-up study of the Danish birth cohorts 1986-1990 compared academic performances of all children having undergone neurosurgeries as infants with a randomly selected, age-matched 5% sample of the same cohorts. The two groups were compared regarding mortality prior to June 1st, 2006, average test scores at ninth grade, and finally the proportion of children not attaining test scores. The exposure group comprised 228 and the control group 14 698 individuals. Hydrocephalus (n = 130), craniotomy (n = 43), and myelomeningocele/enceph...
European journal of anaesthesiology, 2015
A popular advertising campaign in the 1980s and 1990s illustrated the dangers of drug and alcohol... more A popular advertising campaign in the 1980s and 1990s illustrated the dangers of drug and alcohol abuse for the teenage brain by showing a raw egg (‘This is your brain’) being cracked and fried in a pan (‘This is your brain on drugs’). In a sense, this was a simplified representation of the phenotype of drug use in the developing teenage brain (https://www.youtube.com/watch?v=ub_a2t0ZfTs; Accessed June 2014). Currently, researchers are trying to identify whether there exists a neurological phenotype following early childhood exposure to a class of therapeutic drugs, anaesthetics and sedatives. Concerns for potential harmful effects of anaesthetics on brain development in young children undergoing surgical procedures were first raised by animal studies demonstrating widespread cell death of neurones and oligodendrocytes, reductions in neurotrophic factors, alterations in synaptic and dendritic densities, disintegration of the cytoskeleton and long-term neurocognitive impairment following anaesthetic exposure early in life. Subsequently, epidemiological studies established an association between surgical exposure during the first 3 to 4 years of life with learning disabilities, behavioural and developmental
Paediatric anaesthesia, 2015
1 Hansen TG. Anesthesia-related neurotoxicity and the developing animal brain is not a significan... more 1 Hansen TG. Anesthesia-related neurotoxicity and the developing animal brain is not a significant problem in children. Pediatr Anesth 2014; 25: 65–72. 2 Hansen TG, Pedersen JK, Henneberg SW et al. Neurosurgical conditions and procedures in infancy are associated with mortality and academic performances in adolescence: a nationwide cohort study. Pediatr Anesth 2015; 25: 186–192. 3 Wilder RT, Flick RP, Sprung J et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology 2009; 110: 796–804. 4 Hansen TG, Flick R. Anesthetic effects on the developing brain: insights from epidemiology. Anesthesiology 2009; 110: 1–3. 5 Flick RP, Warner DO. A users’ guide to interpreting observational studies of pediatric anesthetic neurotoxicity: the lessons of Sir Bradford Hill. Anesthesiology 2012; 117: 459–462.
Ugeskrift for laeger, Jan 18, 2014
Animal studies (including non-human primates) have shown that most general anaesthetics cause enh... more Animal studies (including non-human primates) have shown that most general anaesthetics cause enhanced neuroapoptosis with subsequent long-term neurocognitive deficits later in life. Some human cohort studies have indicated an association between anaesthesia/surgery and adverse neurocognitive outcome whereas other studies have not. Overall, the data do not justify any change in paediatric anaesthetic clinical practice. Naturally, the risks and benefits of a procedure should always be carefully considered before exposing a child to general anaesthesia.
Paediatric anaesthesia, 2015
A multitude of animal studies have shown that virtually all general anesthetics used in clinical ... more A multitude of animal studies have shown that virtually all general anesthetics used in clinical practice possibly during a vulnerable period of brain development (i.e., brain growth spurt, peak of synaptogenesis) may lead to neurodegeneration (particularly apoptosis) and abnormal synaptic development with functional deficits in learning and behavior later in life. Initial studies were mainly performed in immature rodent pups, but more recent studies have included nonhumans primates (rhesus monkeys). Given the number of neonates, infants, and young children anesthetized annually worldwide, these findings could have significant public health implications. So far, relatively few human (cohort) studies focusing on this topic have been published with inconsistent results. While some studies have indicated an association between exposure to anesthesia and surgery, other studies have indicated no such association. Prospective studies are underway, but the result will not be available for ...
Ugeskrift for laeger, Jan 19, 2007
The practice of paediatric intensive care has matured dramatically over the past 20 years with im... more The practice of paediatric intensive care has matured dramatically over the past 20 years with improving intensive care unit mortality rates and a positive effect on child survival. This paper gives an overview of many of these aspects, and attempts to present a picture of the present situation in Denmark. Internationally, much of this progress has been carried out by means of a strong centralisation of the service, given its low volume, highly specialised and high cost nature. In Denmark, critically ill children are cared for in at least 27 primarily adult intensive care units by nurses and doctors who are not specifically trained in paediatric intensive care. Suggestions for a more centralisation of paediatric intensive care in Denmark are made.
Ugeskrift for laeger, Jan 26, 2005
Propofol infusion syndrome, characterised by cardiovascular collapse, metabolic acidosis, hepatom... more Propofol infusion syndrome, characterised by cardiovascular collapse, metabolic acidosis, hepatomegaly, renal failure and rhabdomyolysis, is a rare and often fatal syndrome seen in critically ill children undergoing long-term propofol sedation. Propofol may impair mitochondrial free fatty acid metabolism, resulting in an imbalance between energy demand and utilisation and thus compromising cardiac and peripheral muscle cell function. Propofol should be used with caution for sedation in critically ill children, as well as for long-term anaesthesia in otherwise healthy children, and doses exceeding 4 mg/kg/h should be avoided.