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Anesthesia in Pediatric Otolaryngology
Abstract
Otolaryngologic procedures in the pediatric population can present unique challenges to the anesthesiologist. Pediatric patients should not be considered “little adults” because they display differences in physical characteristics, physiology, pharmacology, coping strategies, emotional needs, and care coordination compared with the adult population. This chapter focuses on patient optimization, risk evaluation and mitigation, anesthetic concerns for specific pediatric conditions, and the perioperative management of children undergoing otolaryngologic procedures.
Despite numerous applications of Random Forest (RF) techniques in the water-quality field, its use to detect first-flush (FF) events is limited. In this study, we developed a stormwater management framework based on RF algorithms and two different FF definitions (30/80 and M(V) curve). This framework can predict the FF intensity of a single rainfall event for three of the most detected pollutants in urban areas (TSS, TN, and TP), yielding satisfactory results (30/80: accuracyaverage = 0.87; M(V) curve: accuracyaverage = 0.75). Furthermore, the framework can quantify and rank the most critical variables based on their level of importance in predicting FF, using a non-model-biased method based on game theory. Compared to the classical physically-based models that require catchment and drainage information apart from meteorological data, our framework inputs only include rainfall-runoff variables. Furthermore, it is generic and independent from the data adopted in this study, and it can be applied to any other geographical region with a complete rainfall-runoff dataset. Therefore, the framework developed in this study is expected to contribute to accurate FF prediction, which can be exploited for the design of treatment systems aimed to store and treat the FF-runoff volume.
Original research discussing acquired communication disorders caused by electrical trauma which pose unique communication barriers due to their evolving symptom manifestation. As the person ages away from the initial injury, communication barriers can become more pronounced with age.
This presentation provides details explaining how electrical trauma, repeated electrical trauma and lengthy exposure to other forms of non-ionizing radiation can impact speech and communication. Following both UK's National Radiological Protection Board and United States Gulf War Hearing recommendations to study electroconvulsive therapy recipients to better understand the heterogeneity of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. I present four different case studies: Functional NeuroCognitive Imaging results and videos of ECT recipients now living with the neurological sequela of electrical injury which impacts speech and communication. It provides insights into the potential interventions which successfully work for the presenter who lives with speech and communication disorders as a result of chronic electroconvulsive therapy. It identifies strategies to make alternative augmentative communication (AAC) less fatiguing for people who live with a history of chronic exposure to non-ionizing radiation. The presentation concludes with ideas for future research.
-Non-ionizing radiation exposures and subsequent neurodegenerative diseases (Progressive supranuclear palsy and Myoneural Disorders: Amyotrophic Lateral Sclerosis, Motor Neuron Disease and Muscular Sclerosis).
-Immediate and delayed consequences of Electrical Injury/Electromagnetic injury
-Repetitive mild to moderate Traumatic Brain Injuries
-Cognitive communication disorder
-Anoxia/Hypoxia
-Trigeminal, vagal and other cranial nerve dysfunction.
-Electroporation
-Motor Neuron Dysfunction/Motor Neuron Loss
-Demyelination
-Episodic Paroxysmal Neuromuscular Disorders
-Acquired Channelopathies
-Thiols
-Aphasia
-Verbal Apraxia
-Dysarthria, Anarthria
-Preserving residual voice
-Barriers to accessing AAC
-Voice Banking
-AAC Recommendations
The presentation is available with 1.0 CEU through "AAC in the Cloud" website (https://presenters.aacconference.com/videos/UXpVd1FUSXk=)
Background:
In laboratory animals, exposure to most general anaesthetics leads to neurotoxicity manifested by neuronal cell death and abnormal behaviour and cognition. Some large human cohort studies have shown an association between general anaesthesia at a young age and subsequent neurodevelopmental deficits, but these studies are prone to bias. Others have found no evidence for an association. We aimed to establish whether general anaesthesia in early infancy affects neurodevelopmental outcomes.
Methods:
In this international, assessor-masked, equivalence, randomised, controlled trial conducted at 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand, we recruited infants of less than 60 weeks' postmenstrual age who were born at more than 26 weeks' gestation and were undergoing inguinal herniorrhaphy, without previous exposure to general anaesthesia or risk factors for neurological injury. Patients were randomly assigned (1:1) by use of a web-based randomisation service to receive either awake-regional anaesthetic or sevoflurane-based general anaesthetic. Anaesthetists were aware of group allocation, but individuals administering the neurodevelopmental assessments were not. Parents were informed of their infants group allocation upon request, but were told to mask this information from assessors. The primary outcome measure was full-scale intelligence quotient (FSIQ) on the Wechsler Preschool and Primary Scale of Intelligence, third edition (WPPSI-III), at 5 years of age. The primary analysis was done on a per-protocol basis, adjusted for gestational age at birth and country, with multiple imputation used to account for missing data. An intention-to-treat analysis was also done. A difference in means of 5 points was predefined as the clinical equivalence margin. This completed trial is registered with ANZCTR, number ACTRN12606000441516, and ClinicalTrials.gov, number NCT00756600.
Findings:
Between Feb 9, 2007, and Jan 31, 2013, 4023 infants were screened and 722 were randomly allocated: 363 (50%) to the awake-regional anaesthesia group and 359 (50%) to the general anaesthesia group. There were 74 protocol violations in the awake-regional anaesthesia group and two in the general anaesthesia group. Primary outcome data for the per-protocol analysis were obtained from 205 children in the awake-regional anaesthesia group and 242 in the general anaesthesia group. The median duration of general anaesthesia was 54 min (IQR 41-70). The mean FSIQ score was 99·08 (SD 18·35) in the awake-regional anaesthesia group and 98·97 (19·66) in the general anaesthesia group, with a difference in means (awake-regional anaesthesia minus general anaesthesia) of 0·23 (95% CI -2·59 to 3·06), providing strong evidence of equivalence. The results of the intention-to-treat analysis were similar to those of the per-protocol analysis.
Interpretation:
Slightly less than 1 h of general anaesthesia in early infancy does not alter neurodevelopmental outcome at age 5 years compared with awake-regional anaesthesia in a predominantly male study population.
Funding:
US National Institutes of Health, US Food and Drug Administration, Thrasher Research Fund, Australian National Health and Medical Research Council, Health Technologies Assessment-National Institute for Health Research (UK), Australian and New Zealand College of Anaesthetists, Murdoch Children's Research Institute, Canadian Institutes of Health Research, Canadian Anesthesiologists Society, Pfizer Canada, Italian Ministry of Health, Fonds NutsOhra, UK Clinical Research Network, Perth Children's Hospital Foundation, the Stan Perron Charitable Trust, and the Callahan Estate.
Introduction:
Tonsillectomy is considered as a therapeutic option in obstructive sleep apnoea syndrome (OSAS). Postoperative respiratory failure is a complication that can require respiratory support. The main objective of our study is to determine risk factors of postoperative respiratory complications in children undergoing tonsillectomy.
Material and methods:
This is a retrospective single centre observational study including patients with unanticipated postoperative respiratory failure. Patients with a planned preoperative intensive care admission were excluded (age is lower than 2 years, overweight (>95 % percentile of BMI), moderate or severe asthma, major medical conditions). Those patients were compared with randomly selected control patients. Factors studied were: age, weight, indication of surgery, ASA status, preoperative illness conditions, durations of surgery and anaesthesia and administered medications. Statistics used a univariate analyses and a multivariate logistic regression. Results 805 patients underwent adenotonsillectomy during the study period and 25 developed postoperative respiratory failure. These patients were compared to 103 non-complicated control patients. Age (< 4 years), weight (< 18kg), indication of surgery (as SOAS), laryngomalacia, stable and minor congenital cardiac malformation and duration of anaesthesia were found statistically associated. Multivariate analysis found that weight < 18kg is a risk factor associated with the occurrence of postoperative respiratory failure. Overall the model shows a strong accuracy with an area under the curve of ROC analysis of 0.9 [95% confidence interval: 0.85 - 0.95].
Discussion:
our study found that weight < 18kg is a major risk factor for predicting a postoperative respiratory complication.
Dexmedetomidine (Precedex™) may be used as an alternative sedative in children, maintaining spontaneous breathing, and avoiding tracheal intubation in a non-intubated moderate or deep sedation (NI-MDS) approach. This open-label, single-arm, multicenter study evaluated the safety of dexmedetomidine in a pediatric population receiving NI-MDS in an operating room or a procedure room, with an intensivist or anesthesiologist in attendance, for elective diagnostic or therapeutic procedures expected to take at least 30 min. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Patients received one of two doses dependent on age: patients aged ≥28 weeks' gestational age to <1 month postnatal received dose level 1 (0.1 μg/kg load; 0.05–0.2 μg/kg/h infusion); those aged 1 month to <17 years received dose level 2 (1 μg/kg load; 0.2–2.0 μg/kg/h infusion). Sedation efficacy was assessed and defined as adequate sedation for at least 80% of the time and successful completion of the procedure without the need for rescue medication. In all, 91 patients were enrolled (dose level 1, n = 1; dose level 2, n = 90); of these, 90 received treatment and 82 completed the study. Eight patients in dose level 2 discontinued treatment for the following reasons: early completion of diagnostic or therapeutic procedure (n = 3); change in medical condition (need for intubation) requiring deeper level of sedation (n = 2); adverse event (AE; hives and emesis), lack of efficacy, and physician decision (patient not sedated enough to complete procedure; n = 1 each). Sixty-seven patients experienced 147 TEAEs. The two most commonly reported AEs were respiratory depression (bradypnea; reported per protocol-defined criteria, based on absolute respiratory rate values for age or relative decrease of 30% from baseline) and hypotension. Four patients received glycopyrrolate for bradycardia and seven patients received intravenous fluids for hypotension. SpO2 dropped by 10% in two patients, but resolved without need for manual ventilation. All other reported AEs were consistent with the known safety profile of dexmedetomidine. Two of the 78 patients in the efficacy-evaluable population met all sedation efficacy criteria. Dexmedetomidine was well-tolerated in pediatric patients undergoing procedure-type sedation.
Background:
Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising fetal haemoglobin. This is an update of a previously published Cochrane Review.
Objectives:
To assess the effects of hydroxyurea therapy in people with SCD (all genotypes), of any age, regardless of setting.
Search methods:
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Register, comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries.Date of the most recent search: 16 January 2017.
Selection criteria:
Randomised and quasi-randomised controlled trials, of one month or longer, comparing hydroxyurea with placebo, standard therapy or other interventions for people with SCD.
Data collection and analysis:
Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias.
Main results:
Seventeen studies were identified in the searches; eight randomised controlled trials were included, recruiting 899 adults and children with SCD (haemoglobin SS (HbSS), haemoglobin SC (HbSC) or haemoglobin Sβºthalassaemia (HbSβºthal) genotypes). Studies lasted from six to 30 months.Four studies (577 adults and children with HbSS or HbSβºthal) compared hydroxyurea to placebo; three recruited individuals with only severe disease and one recruited individuals with all disease severities. There were statistically significant improvements in terms of pain alteration (using measures such as pain crisis frequency, duration, intensity, hospital admissions and opoid use), measures of fetal haemoglobin and neutrophil counts and fewer occurrences of acute chest syndrome and blood transfusions in the hydroxyurea groups. There were no consistent statistically significant differences in terms of quality of life and adverse events (including serious or life-threatening events). Seven deaths occurred during the studies, but the rates by treatment group were not statistically significantly different.Two studies (254 children with HbSS or HbSβºthal also with risk of primary or secondary stroke) compared hydroxyurea and phlebotomy to transfusion and chelation; there were statistically significant improvements in terms of measures of fetal haemoglobin and neutrophil counts, but more occurrences of acute chest syndrome and infections in the hydroxyurea and phlebotomy group. There were no consistent statistically significant differences in terms of pain alteration and adverse events (including serious or life-threatening events). Two deaths occurred during the studies (one in a the hydroxyurea treatment arm and one in the control arm), but the rates by treatment group were not statistically significantly different. In the primary prevention study, no strokes occurred in either treatment group but in the secondary prevention study, seven strokes occurred in the hydroxyurea and phlebotomy group (none in the transfusion and chelation group) and the study was terminated early.The quality of the evidence for the above two comparisons was judged as moderate to low as the studies contributing to these comparisons were mostly large and well designed (and at low risk of bias); however evidence was limited and imprecise for some outcomes such as quality of life, deaths during the studies and adverse events and results are applicable only to individuals with HbSS and HbSβºthal genotypes.Of the remaining two studies, one (22 children with HbSS or HbSβºthal also at risk of stoke) compared hydroxyurea to observation; there were statistically significant improvements in terms of measures of fetal haemoglobin and neutrophil counts but no statistically significant differences in terms of adverse events (including serious or life-threatening events).The final study (44 adults and children with HbSC) compared treatment regimens with and without hydroxyurea - there was statistically significant improvement in terms of measures of fetal haemoglobin, but no statistically significant differences in terms of adverse events (including serious or life-threatening events). No participants died in either of these studies and other outcomes relevant to the review were not reported.The quality of the evidence for the above two comparisons was judged to be very low due to the limited number of participants, the lack of statistical power (as both studies were terminated early with approximately only 20% of their target sample size recruited) and the lack of applicability to all age groups and genotypes.
Authors' conclusions:
There is evidence to suggest that hydroxyurea is effective in decreasing the frequency of pain episodes and other acute complications in adults and children with sickle cell anaemia of HbSS or HbSβºthal genotypes and in preventing life-threatening neurological events in those with sickle cell anaemia at risk of primary stroke by maintaining transcranial doppler velocities. However, there is still insufficient evidence on the long-term benefits of hydroxyurea, particularly in preventing chronic complications of SCD, recommending a standard dose or dose escalation to maximum tolerated dose. There is also insufficient evidence about the long-term risks of hydroxyurea, including its effects on fertility and reproduction. Evidence is also limited on the effects of hydroxyurea on individuals with HbSC genotype. Future studies should be designed to address such uncertainties.
Background
Dexmedetomidine can facilitate a smooth extubation process and reduce the requirement of sevoflurane and emergence agitation when administrated perioperatively. We aimed to observe the extubation process and the recovery characteristics in pediatric patients undergoing tonsillectomy while anesthetized with either high-concentration sevoflurane alone or low-concentration sevoflurane combined with pre-medication of single dose of intravenous dexmedetomidine. Methods
Seventy-five patients (ASA I or II, aged 3–7 years) undergoing tonsillectomy were randomized into three equal groups: to receive intravenous saline (Group D0), dexmedetomidine 1 μg/kg (Group D1), or dexmedetomidine 2 μg/kg (Group D2) approximately 10 min before anesthesia. Before the end of surgery, sevoflurane were adjusted to 1.5 times, 1.0 time and 0.8 times the minimal effective concentration in groups D0, D1 and D2, respectively. The sevoflurane concentration for each group was maintained for at least 10 min before the tracheal deep-extubation was performed. The extubation event, recovery characteristics and post-op respiratory complications were recorded. ResultsAll tracheal tubes in three groups were removed successfully during deep anesthesia. Nine patients in Group D0, three patients in Group D1, and two patients in Group D2 required oral airway to maintain a patent airway after extubation. The frequency of oral airway usage in groups D1 and D2 were significantly lower than that in Group D0. The percentages of patients with ED and the requirements of fentanyl in groups D1 and D2 were also significantly lower than those in Group D0. The time from extubation to spontaneous eye opening in Group D2 was longer than that in groups D0 and D1. The times of post-anesthesia care unit discharge in groups D0 and D2 were longer than that in Group D1. No other respiratory complications and vomiting were observed. ConclusionA single dose of intravenous dexmedetomidine as pre-medication in combination with low-concentration sevoflurane at the end of surgery provided safe and smooth deep extubation condition and it also lowered the emergence agitation in sevoflurane-anaesthetized children undergoing tonsillectomy. Preoperative dexmedetomidine at 1 μg/kg did not prolong postoperative recovery time. Trial registrationChinese Clinical Trial Registry (ChiCTR): ChiCTR-IOR-16008423, date of registration: 06 may 2016.
Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades, and involves the cornerstone metabolic pathways which take place in the microsomes within hepatocytes. APAP hepatotoxicity remains a global issue; in the United States, in particular, it accounts for more than 50% of overdose-related acute liver failure and approximately 20% of the liver transplant cases. The pathophysiology, disease course and management of acute liver failure secondary to APAP toxicity remain to be precisely elucidated, and adverse patient outcomes with increased morbidity and mortality continue to occur. Although APAP hepatotoxicity follows a predictable timeline of hepatic failure, its clinical presentation might vary. N-acetylcysteine (NAC) therapy is considered as the mainstay therapy, but liver transplantation might represent a life-saving procedure for selected patients. Future research focus in this field may benefit from shifting towards obtaining antidotal knowledge at the molecular level, with focus on the underlying molecular signaling pathways.
A retrospective study was conducted to assess the value of the chest x-ray as a preoperative screening procedure in pediatric patients. Admissions for elective surgery were compared at two hospitals, one that required routine preoperative chest x-rays and one that did not. Our purpose was to determine the yield of the screening chest x-ray in detecting unknown abnormalities and to determine whether patients who had a preoperative chest x-ray taken experienced fewer anesthetic or postoperative complications than did those who did not. In all, 1,924 cases were studied; in 749 a preoperative chest film was taken. Of those 749 cases, a previously unsuspected abnormality was discovered in 35 (4.7%) patients. Nine (1.2%) of these abnormalities were considered to be clinically significant and three (0.4%) resulted in cancellation of surgery. No differences in anesthetic or postoperative complications were noted between the two groups of patients. It is recommended that the performance of routine preoperative chest x-rays on apparently healthy children be discontinued.
To assess the value of routine preoperative chest x-ray films in pediatric patients, a prospective study of 1,500 patients, ages newborn to 19 years, was undertaken. Of all the patients, 7.5% demonstrated at least one roentgenographic abnormality, with 4.7% of the patients demonstrating a totally unsuspected significant roentgenographic anomaly. In 3.8% of the patients, surgery was either postponed or cancelled or the anesthetic technique was altered as a result of the roentgenographic finding. It is believed that the routine preoperative chest film is justified if the film is evaluated before surgery and the results clinically followed up.
OBJECTIVE
To report three cases of meperidine-related seizures when meperidine was administered via patient-controlled analgesia pump (PCAP) and to review literature related to meperidine-associated seizures.
DATA SOURCES
Case reports and review articles identified by a computerized search (MEDLINE) and manual search ( Index Medicus).
DATA SYNTHESIS
PCAPs are being used frequently to relieve the pain of sickle cell crisis as well as pain from many other etiologies. We report three cases of meperidine-related seizures associated with its administration via PCAP. Each of the patients received either relatively high doses, long-term therapy, or both. Meperidine has been associated with seizure activity when administered via traditional routes. Previously identified risk factors for the development of meperidine-related seizures include renal failure, high meperidine dosages, and coadministration of hepatic enzyme-inducing medications or phenothiazines.
CONCLUSIONS
Meperidine administered via PCAP may be associated with seizures. Optimally, an alternative analgesic should be administered when this route is used.
From 1978 to 1988, The Cooperative Study of Sickle Cell Disease observed 3,765 patients with a mean follow-up of 5.3 +/- 2.0 years. One thousand seventy-nine surgical procedures were conducted on 717 patients (77% sickle cell anemia [SS], 14% sickle hemoglobin C disease [SC], 5.7% S beta zero thalassemia, 3% S beta zero + thalassemia). Sixty-nine percent had a single procedure, 21% had two procedures, and the remaining 11% had more than two procedures during the study follow- up. The most frequent procedure was abdominal surgery for cholecystectomy or splenectomy (24% of all surgical procedures, N = 258). Of these, 93% received blood transfusion, and there was no association between preoperative hemoglobin A level and complication rates (except reduction in pain crisis). Overall mortality within 30 days of a surgical procedure was 1.1% (12 deaths after 1,079 surgical procedures). Three deaths were considered to be related to the surgical procedure and/or anesthesia (0.3%). No deaths were reported in patients younger than 14 years of age. Sickle cell diseases (SCD)-related complications after surgery were more frequent in SS patients who received regional compared with general anesthesia (adjusted for risk level of the surgical procedure, patient age, and preoperative transfusion status, P = .058). Non-SCD-related postoperative complications were higher in both SS and SC patients who received regional compared with those who received general anesthesia (P =.095). Perioperative transfusion was associated with a lower rate of SCD- related postoperative complications for SS patients undergoing low-risk procedures (P = .006, adjusted for age and type of anesthesia), with crude rated of 12.9% without transfusion compared with 4.8% with transfusion. In SC patients, preoperative transfusion was beneficial for all surgical risk levels (P = .009). Thus, surgical procedures can be performed safely in patients with SCD.
Postoperative nausea and vomiting (PONV) occurs in approximately 30 percent of patients undergoing surgery. It can cause patient dissatisfaction, significant clinical complications and economical loss. In PONV management, patient risk should be determined, risk reducing measures should be implemented, dosing and timing of antiemetic prophylaxis should be determined and an algorithm including rescue treatment for each patient should be generated. In this review, pathophysiology, risk factors, prevention and treatment of PONV are presented.
Background:
Opioid analgesics are frequently prescribed to manage acute and chronic pain, but individual differences in opioid response make effective pain control in all patients an elusive goal. Furthermore, the risk of addiction following opioid consumption varies among individual patients. Although many psychosocial factors contribute to an individual's opioid response and risk for addiction, a strong genetic component has also been demonstrated.
Content:
Opioids undergo substantial enzymatic modification that can generate metabolites with either increased or decreased opioid activity relative to the parent compound. To elicit their analgesic effect, parent compounds and active metabolites must be transported into the central nervous system where they bind to opioid receptors and inhibit neurotransmission. Inherited genetic variants that alter the function of proteins involved in these processes have been associated with differences in opioid response and risk for addiction. Detection of these variants can help guide opioid selection, inform dosing decisions, or encourage use of a nonopioid analgesic.
Summary:
Whereas some genetic variants are clearly associated with differences in opioid response and have been included in consensus clinical practice guidelines, the impact of other variants on opioid response remains unclear. Studies performed to date have generated promising results, but inconsistent findings, reimbursement challenges, and the lack of robust decision support tools have hampered widespread adoption of pharmacogenetic testing to guide pain management treatment decisions. Future work involving the simultaneous evaluation of large numbers of variants and demonstration of a clear clinical benefit provided by pharmacogenetic testing will be required to overcome these obstacles.
Background:
Few studies of how exposure of children to anesthesia may affect neurodevelopment employ comprehensive neuropsychological assessments. This study tested the hypothesis that exposure to multiple, but not single, procedures requiring anesthesia before age 3 yr is associated with adverse neurodevelopmental outcomes.
Methods:
Unexposed, singly exposed, and multiply exposed children born in Olmsted County, Minnesota, from 1994 to 2007 were sampled using a propensity-guided approach and underwent neuropsychological testing at ages 8 to 12 or 15 to 20 yr. The primary outcome was the Full-Scale intelligence quotient standard score of the Wechsler Abbreviated Scale of Intelligence. Secondary outcomes included individual domains from a comprehensive neuropsychological assessment and parent reports.
Results:
In total, 997 children completed testing (411, 380, and 206 unexposed, singly exposed, and multiply exposed, respectively). The primary outcome of intelligence quotient did not differ significantly according to exposure status; multiply exposed and singly exposed children scoring 1.3 points (95% CI, -3.8 to 1.2; P = 0.32) and 0.5 points (95% CI, -2.8 to 1.9; P = 0.70) lower than unexposed children, respectively. For secondary outcomes, processing speed and fine motor abilities were decreased in multiply but not singly exposed children; other domains did not differ. The parents of multiply exposed children reported increased problems related to executive function, behavior, and reading.
Conclusions:
Anesthesia exposure before age 3 yr was not associated with deficits in the primary outcome of general intelligence. Although secondary outcomes must be interpreted cautiously, they suggest the hypothesis that multiple, but not single, exposures are associated with a pattern of changes in specific neuropsychological domains that is associated with behavioral and learning difficulties.
Recently it was demonstrated that exposure of the developing brain during the period of synaptogenesis to drugs that block NMDA glutamate receptors or drugs that potentiate GABA A receptors can trigger widespread apoptotic neurodegeneration. All currently used general anesthetic agents have either NMDA receptor-blocking or GABA A receptor-enhancing properties. To induce or maintain a surgical plane of anesthesia, it is common practice in pediatric or obstetrical medicine to use agents from these two classes in combination. Therefore, the question arises whether this practice entails significant risk of inducing apoptotic neurodegeneration in the developing human brain. To begin to address this problem, we have administered to 7-d-old infant rats a combination of drugs commonly used in pediatric anesthesia (midazolam, nitrous oxide, and isoflurane) in doses sufficient to maintain a surgical plane of anesthesia for 6 hr, and have observed that this causes widespread apoptotic neurodegeneration in the developing brain, deficits in hippocampal synaptic function, and persistent memory/learning impairments.
Background:
Limited evidence suggests that children have a lower incidence of perioperative respiratory adverse events when intravenous propofol is used compared with inhalational sevoflurane for the anesthesia induction. Limiting these events can improve recovery time as well as decreasing surgery waitlists and healthcare costs. This single center open-label randomized controlled trial assessed the impact of the anesthesia induction technique on the occurrence of perioperative respiratory adverse events in children at high risk of those events.
Methods:
Children (N = 300; 0 to 8 yr) with at least two clinically relevant risk factors for perioperative respiratory adverse events and deemed suitable for either technique of anesthesia induction were recruited and randomized to either inhalational sevoflurane or intravenous propofol. The primary outcome was the difference in the rate of occurrence of perioperative respiratory adverse events between children receiving intravenous induction and those receiving inhalation induction of anesthesia.
Results:
Children receiving inhalational sevoflurane were significantly more likely to experience perioperative respiratory adverse events compared with those who received intravenous propofol after adjusting for age, sex, American Society of Anesthesiologists physical status and weight (perioperative respiratory adverse event: 39/149 [26%] vs. 64/149 [10.7%], relative risk [RR]: 1.7, 95% CI: 1.2 to 2.3, P = 0.002, respiratory adverse events at induction: 47/149 [31.5%] vs. 16/149 [10.7%], RR: 3.06, 95% CI: 1.81 to 5.16, P < 0.001).
Conclusions:
Where clinically appropriate, anesthesiologists should consider using an intravenous propofol induction technique in children who are at high risk of experiencing perioperative respiratory adverse events.
SmartTots (http://smarttots.org/) represents a public-private partnership between the International Anesthesia Research Society and the US Food and Drug Administration. Over the past 7 years, SmartTots has worked in collaboration with various stakeholders to determine whether anesthetic drugs have detrimental effects on the developing brain. SmartTots has funded clinical and preclinical studies, organized meetings, served as a repository of peer-reviewed information, and facilitated the development of consensus-based statements. Here, we report advances in the field of anesthetic neurotoxicity and provide an update on SmartTots' activities. Clinical studies have provided some reassurance that a brief exposure to anesthetic drugs does not cause overt, persistent cognitive deficits. New recommendations aim to increase the reproducibility and "clinical relevance" of data from studies of laboratory animals. Overall, the field has advanced substantially; however, it remains paramount to definitively resolve whether anesthetic drugs are neurotoxic to the immature brain. The results of SmartTots efforts will either ally unwarranted fears or substantially change pediatric anesthetic practice and prompt studies to identify neuroprotective strategies.
Objective
To bring attention to the epidemiology, prevention, management, and consequences of surgical fires in otolaryngology by reviewing the literature.
Data Sources
PubMed, EMBASE, Web of Science, and Scopus.
Review Methods
Comprehensive search terms were developed, and searches were performed from data source inception through August 2016. A total of 4506 articles were identified; 2351 duplicates were removed; and 2155 titles and abstracts were independently reviewed. Reference review was also performed. Eligible manuscripts described surgical fires involving patients undergoing otolaryngologic procedures.
Results
Seventy-two articles describing 87 otolaryngologic surgical fire cases were identified. These occurred during oral cavity or oropharyngeal procedures (11%), endoscopic laryngotracheal procedures (25%), tracheostomies (36%), “other” general anesthesia procedures (3%), and monitored anesthesia care or local procedures (24%). Oxidizing agents consisted of oxygen alone (n = 63 of 81, 78%), oxygen and nitric oxide (n = 17 of 81, 21%), and room air (n = 1 of 81, 1%). The fractional inspired oxygen delivered was >30% in 97% of surgical fires in non–nitrous oxide general anesthesia cases (n = 35 of 36). Laser-safe tubes were used in only 12% of endoscopic laryngotracheal cases with endotracheal tube descriptions (n = 2 of 17). Eighty-six percent of patients experienced acute complications (n = 76 of 87), including 1 intraoperative death, and 22% of patients (n = 17 of 77) experienced long-term complications.
Conclusion
Surgical fires in otolaryngology persist despite aggressive multi-institutional efforts to curb their incidence. Guideline recommendations to minimize the concentration of delivered oxygen and use laser-safe tubes when indicated were not observed in many cases. Improved institutional fire safety practices are needed nationally and internationally.
Lean body mass is commonly proposed for anesthesia maintenance drug dosing calculations. However, total body mass used with allometric scaling has been shown to be better for propofol in obese adults and children. Fat-free mass has also been used instead of lean body mass. Fat-free mass is essentially the same as lean body mass but excludes a small percentage of mass of lipids in cell membranes, CNS, and bone marrow. Normal fat mass is a size descriptor that partitions total body mass into fat-free mass and fat mass calculated from total body mass minus fat-free mass. The relative influence of fat mass compared with fat-free mass is described by the fraction of fat mass that makes fat equivalent to fat-free mass in terms of allometric size. This fraction (Ffat) will differ for each drug and each parameter affected by body size (eg, clearance and volume of distribution). This fraction is based on the concept of theory-based allometric size. The normal fat mass based on allometric theory and partition of body mass into fat and fat-free components provides a principle-based approach explaining size and body composition effects on pharmacokinetics of all drugs in children and in adults.
Surgery under apnoeic conditions with the use of high-flow nasal oxygen is novel. Between November 2016 and May 2017, 28 patients underwent tubeless laryngeal or tracheal surgery under apnoeic conditions with high-flow nasal oxygen as the sole method of gas exchange. Patients received total intravenous anaesthesia and neuromuscular blocking agents for the duration of their surgery. The median (IQR [range]) apnoea time was 19 (15–24 [9–37]) min. Four patients experienced an episode of oxygen desaturation to a value between 85% and 90%, lasting less than 2 min in each case. Median (IQR [range]) end-tidal carbon dioxide (ETCO2) level following apnoea was 8.2 (7.2–9.4 [5.8–11.8]) kPa. The mean (SD) rate of ETCO2 increase was 0.17 (0.07) kPa.min−1 from an approximated baseline value of 5.00 kPa. Venous blood sampling from 19 patients demonstrated a mean (SD) partial pressure of carbon dioxide (PVCO2) of 6.29 (0.71) kPa at baseline and 9.44 (1.12) kPa after 15 min of apnoea. This equates to a mean (SD) PVCO2 rise of 0.21 (0.08) kPa.min−1 during this period. Mean (SD) pH was 7.40 (0.03) at baseline and 7.23 (0.04) after 15 min of apnoea. Mean (SD) standard bicarbonate was 26.7 (1.8) mmol.l−1 at baseline and 25.4 (1.8) mmol.l−1 at 15 min. We conclude that high-flow nasal oxygen under apnoeic conditions can provide satisfactory gas exchange in order to allow tubeless anaesthesia for laryngeal surgery.
Aspiration of foreign-bodies remains a major life-threatening situation in children and have always been a source of interest and confusion to otolaryngologists due to their varied presentations. These conditions if not promptly diagnosed and managed can prove to be fatal, but the current mortality is only one percent compared to pre bronchoscopy era (Rothman and Boeckman in Ann Otol Rhinol Laryngol 89:434–436, 1980). Peak incidence of this condition is in early childhood due to child’s habit of putting small objects in mouth to determine their taste and texture and chew while teething. This is a study conducted retrospectively from 2012 to 2017 in a teritiary care center. It includes a total of 70 cases of foreign body in airway who underwent rigid bronchoscopy under general anaesthesia. The patients were all in paediatric age group but mostly between 6 months to 3 years. The youngest patient was 3 months old and the oldest 12 years old. Male children (70%, n = 49) were more common than female children (30%, n = 21) with a male to female ratio of 2.33:1. A definite history of foreign body aspiration was given in only 70% cases, but the most common symptom were cough (100%) and breathlessness (80%). Organic foreign bodies (76.36%, n = 42) were more common when compared to inorganic foreign bodies. Foreign body most commonly impacted in Right main bronchus (49.09%, n = 27) followed by Left main bronchus (31.42%) and lastly the trachea (19.49%). Even though the mortality in patients of foreign body aspiration is low, it is essential to have proper cooperation between the otolaryngologists, paediatrician and the radiologist for rapid diagnosis and prompt management. It is advised to have a second look to check all the bronchopulmonary segments. Life saving steps are Prompt referral, early diagnosis and vigilant management.
Understanding the pharmacologic options for pediatric sedation outside the operating room will allow practitioners to formulate an ideal anesthetic plan, allaying anxiety and achieving optimal immobilization while ensuring rapid and efficient recovery. The authors identified relevant medical literature by searching PubMed, MEDLINE, Embase, Scopus, Web of Science, and Google Scholar databases for English language publications covering a period from 1984 to 2017. Search terms included pediatric anesthesia, pediatric sedation, non-operating room sedation, sedation safety, and pharmacology. As a narrative review of common sedation/anesthesia options, the authors elected to focus on studies, reviews, and case reports that show clinical relevance to modern day sedation/anesthesia practice. A variety of pharmacologic agents are available for sedation/anesthesia in pediatrics, including midazolam, fentanyl, ketamine, dexmedetomidine, etomidate, and propofol. Dosing ranges reported are a combination of what is discussed in the reviewed literature and text books along with personal recommendations based on our own practice. Several reports reveal that ketofol (a combination of ketamine and propofol) is quite popular for short, painful procedures. Fospropofol is a newer-generation propofol that may confer advantages over regular propofol. Remimazolam combines the pharmacologic effects of remifentanil and midazolam. A variety of etomidate derivatives such as methoxycarbonyl-etomidate, carboetomidate, methoxycarbonyl-carboetomidate, and cyclopropyl-methoxycarbonyl metomidate are in development stages. The use of nitrous oxide as a mild sedative, analgesic, and amnestic agent is gaining popularity, especially in the ambulatory setting. Utilizing a dedicated and experienced team to provide sedation enhances safety. Furthermore, limiting sedation plans to single-agent pharmacy appears to be safer than using multi-agent plans.
Background. High-flow nasal oxygen (HFNO) has been shown to benefit oxygenation, ventilation and upper airway patency in a range of clinical scenarios, however its use in spontaneously breathing patients during general anaesthesia has not been described. Spontaneous respiration using i.v. anaesthesia is the primary technique used at our institution for tubeless airway surgery. We hypothesized that the addition of HFNO would increase our margin of safety, particularly during management of an obstructed airway.
Methods. A retrospective observational study was conducted using a SponTaneous Respiration using IntraVEnous anaesthesia and High-flow nasal oxygen (STRIVE Hi) technique to manage 30 adult patients undergoing elective laryngotracheal surgery.
Results. Twenty-six patients (87%) presented with significant airway and/or respiratory compromise (16 were stridulous, 10 were dyspnoeic). No episodes of apnoea or complete airway obstruction occurred during the induction of anaesthesia using STRIVE Hi. The median [IQR (range)] lowest oxygen saturation during the induction period was 100 [99–100 (97–100)] %. The median [IQR (range)] overall duration of spontaneous ventilation was 44 [40–49.5 (18–100)] min. The median [IQR (range)] end-tidal carbon dioxide (ETCO2) level at the end of the spontaneous ventilation period was 6.8 [6.4–7.1 (4.8–8.9)] kPa. The mean rate of increase in ETCO2 was 0.03 kPa min⁻¹.
Conclusions. STRIVE Hi succeeded in preserving adequate oxygen saturation, end-tidal carbon dioxide and airway patency. We suggest that the upper and lower airway benefits attributed to HFNO, are ideally suited to a spontaneous respiration induction, increasing its margin of safety. STRIVE Hi is a modern alternative to the traditional inhalation induction.
Purpose:
Approximately 200,000 individuals worldwide are born annually with sickle cell disease (SCD). Regions with the highest rates of SCD include Africa, the Mediterranean, and Asia, where its prevalence is estimated to be 2-6% of the population. An estimated 70,000-100,000 people in the United States have SCD. Due to enhanced newborn screening, a better understanding of this disease, and more aggressive therapy, many sickle cell patients survive into their adult years and present more frequently for surgery.
Source:
The authors identified relevant medical literature by searching PubMed, MEDLINE®, EMBASE™, Scopus™, Web of Science, and Google Scholar databases for English language publications appearing from 1972-September 2016. Case reports, abstracts, review articles, and original research articles were reviewed-with particular focus on the pathophysiology and medical management of SCD and any anesthesia-related issues.
Principal findings:
Perioperative physicians should be familiar with the triggers of a sickle cell crisis and vaso-occlusive disease. Sickle cell disease affects various organ systems, including the central nervous, cardiovascular, pulmonary, genitourinary, and musculoskeletal systems. Preoperative assessment should focus on end-organ dysfunction. Controversy continues regarding if and when sickle cell patients should receive transfusions and which anesthetic technique (regional or general) confers any benefits. Timely, appropriate, and sufficient analgesia is critical, especially when patients experience a vaso-occlusive crisis, acute chest syndrome, or acute postoperative pain.
Conclusion:
Effective management of SCD patients in the perioperative setting requires familiarity with the epidemiology, pathophysiology, clinical manifestations, and treatment of SCD.
Pulmonary hypertension (PH) is a complex disease process of the pulmonary vasculature system characterized by elevated pulmonary arterial pressures. Patients with PH are at increased risk for morbidity and mortality, including intraoperatively and postoperatively. Appreciation by the clinical anesthesiologist of the pathophysiology of PH is warranted. Careful and meticulous strategy using appropriate anesthetic medications, pulmonary vasodilator and inotropic agents, and careful fluid management all increase the likelihood of the best possible outcome in this challenging patient population.
Background:
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.
Methods:
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 with ClinicalTrials.gov, number NCT01878760.
Findings:
Between April 1, 2014, and Jan 31, 2015, 31?127 anaesthetic procedures in 30?874 children with a mean age of 6?35 years (SD 4?50) were included. The incidence of perioperative severe critical events was 5?2% (95% CI 5?0-5?5) with an incidence of respiratory critical events of 3?1% (2?9-3?3). Cardiovascular instability occurred in 1?9% (1?7-2?1), with an immediate poor outcome in 5?4% (3?7-7?5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10?000. This was independent of type of anaesthesia. Age (relative risk 0?88, 95% CI 0?86-0?90; p<0?0001), medical history, and physical condition (1?60, 1?40-1?82; p<0?0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0?99, 0?981-0?997; p<0?0048 for respiratory critical events, and 0?98, 0?97-0?99; p=0?0039 for cardiovascular critical events), rather than the type of health institution or providers.
Interpretation:
This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia.
Funding:
European Society of Anaesthesiology.
Approximately 31.8% of U.S. children ages 2 to 19 years are considered overweight or obese. This creates significant challenges to dosing medications that are primarily weight based (mg/kg) and in predicting pharmacokinetics parameters in pediatric patients. Obese individuals generally have a larger volume of distribution for lipophilic medications. Conversely, the Vd of hydrophilic medications may be increased or decreased due to increased lean body mass, blood volume, and decrease percentage of total body water. They may also experience decreased hepatic clearance secondary to fatty infiltrates of the liver. Hence, obesity may affect loading dose, dosage interval, plasma half-life, and time to reach steady-state concentration for various medications. Weight-based dosing is also a cause for potential medication errors. This position statement of the Pediatric Pharmacy Advocacy Group recommends that weight-based dosing should be used in patients ages < 18 years who are < 40 kg; weight-based dosing should ...
Background:
Despite its widespread use, the American Society of Anesthesiologists (ASA)-Physical Status Classification System has been shown to result in inconsistent assignments among anesthesiologists. The ASA-Physical Status Classification System is also used by nonanesthesia-trained clinicians and others. In 2014, the ASA developed and approved examples to assist clinicians in determining the correct ASA-Physical Status Classification System assignment. The effect of these examples by anesthesia-trained and nonanesthesia-trained clinicians on appropriate ASA-Physical Status Classification System assignment in hypothetical cases was examined.
Methods:
Anesthesia-trained and nonanesthesia-trained clinicians were recruited via email to participate in a web-based questionnaire study. The questionnaire consisted of 10 hypothetical cases, for which respondents were first asked to assign ASA-Physical Status using only the ASA-Physical Status Classification System definitions and a second time using the newly ASA-approved examples.
Results:
With ASA-approved examples, both anesthesia-trained and nonanesthesia-trained clinicians improved in mean number of correct answers (out of possible 10) compared to ASA-Physical Status Classification System definitions alone (P < 0.001 for all). However, with examples, nonanesthesia-trained clinicians improved more compared to anesthesia-trained clinicians. With definitions only, anesthesia-trained clinicians (5.8 ± 1.6) scored higher than nonanesthesia-trained clinicians (5.4 ± 1.7; P = 0.041). With examples, anesthesia-trained (7.7 ± 1.8) and nonanesthesia-trained (8.0 ± 1.7) groups were not significantly different (P = 0.100).
Conclusions:
The addition of examples to the definitions of the ASA-Physical Status Classification System increases the correct assignment of patients by anesthesia-trained and nonanesthesia-trained clinicians.
There remain unanswered questions and implications related to emergence delirium in children. Although we know that there are some predisposing factors to emergence delirium, we still are unable to predict accurately those who are at greatest risk. Emergence delirium should be considered as a ‘vital sign’, which should be followed and documented in every child in the postanaesthesia recovery period. Standardized screening tools should be adopted for paediatric emergence delirium.
Objective:
The American Society of Anesthesiologists physical status (ASA-PS) is associated with increased morbidity and mortality in the perioperative period. When surgeries are scheduled by surgeons and their staff at our large institution a presumed ASA-PS is chosen. This is because our institution (and, anecdotally, others in our hospital system and elsewhere), recognizing the relationship between higher ASA-PS and poorer postoperative outcomes, requires all patients with higher ASA-PS levels (≥3) to undergo enhanced preoperative workup. The patients may not, however, necessarily be seen in the anesthesia clinic prior to surgery. As a result, patients are assigned a presumed ASA-PS by a non-anesthesia provider (e.g., surgeons and physician extenders) that may not reflect the ASA-PS chosen by the anesthesiologist on the day of surgery. Errors in the accuracy of the ASA-PS prior to surgery lead to unnecessary and costly preoperative testing, delays in operative procedures, and potential case cancellations. Our study aimed to determine whether there are significant differences in the assignment of ASA-PS by non-anesthesia providers when compared to anesthesia providers.
Design:
We administered an IRB-approved survey asking the ASA-PS of 20 hypothetical case vignettes to 229 clinicians in various departments. Responses by non-anesthesia providers were compared to the consensus of the department of anesthesiology.
Setting:
Faculty office spaces and conferences.
Patients:
No patients, physicians only.
Interventions:
Survey administration.
Measurements:
ASA-PS scores acquired from surveys.
Main results:
Residents and faculty in the department of anesthesiology demonstrated no statistical difference in the median ASA score in 19/20 case scenarios. All other departments were statistically different when compared to the department of anesthesiology (p<0.05). The probability of a department either over- or under-rating the ASA-PS was calculated, and is summarized in Fig. 3. All departments, except anesthesiology, had a 30-40% chance of under-rating the ASA-PS of the patients in the clinical vignettes.
Conclusions:
Non-anesthesia providers assign ASA-PS with significantly less accuracy than do anesthesia providers, even when adjusted for multiple comparisons. Surgical and procedural departments were found to consistently under-rate the ASA-PS of patients in our clinical vignettes.
The FDA has issued a warning regarding use of general anesthetic and sedation drugs in children under 3 years of age and in pregnant women in their third trimester — a warning that will change practice and raise questions that currently have no clear answers.
In this prospective, randomized, double-blind study, we compared the efficacy and safety of ondansetron and metoclopramide in the treatment of postoperative nausea and vomiting (PONV). One hundred seventyfive patients with PONV during recovery from anesthesia for gynecological laparoscopy were treated intravenously with either ondansetron 4 mg (58 patients), metoclopramide 10 mg (57 patients), or placebo (60 patients). Early antiemetic efficacy (abolition of vomiting within 10 min and of nausea within 30 min from the administration of the study drugs with no further vomiting or nausea episodes during the first hour) was obtained in 54 of 58 patients (93.1%) in the ondansetron group, in 38 of 57 patients (66.7%) in the metoclopramide group, and in 21 of 60 patients (35%) in the placebo group (P < 0.001). This difference was still significant when controlling for age, body weight, history of motion sickness, previous PONV episodes, duration of anesthesia, and intraoperative fentanyl consumption using a logistic model. Early antiemetic efficacy was inversely related to the amount of fentanyl administered during anesthesia, regardless of treatment. According to the Kaplan-Meier method, the probability of remaining PONV-free for 48 h after a successful treatment was 0.59 (95% confidence interval 0.45-0.71) in the ondansetron group, 0.45 (0.29-0.60) in the metoclopramide group, and 0.33 (0.15-0.53) in the placebo group (P = 0.003). In conclusion, ondansetron 4 mg is more effective than metoclopramide 10 mg and placebo in the treatment of established PONV.
(Anesth Analg 1997;85:395-9)
Sickle cell disease is a common and life-threatening haematological disorder that affects millions of people worldwide. Abnormal sickle-shaped erythrocytes disrupt blood flow in small vessels, and this vaso-occlusion leads to distal tissue ischaemia and inflammation, with symptoms defining the acute painful sickle-cell crisis. Repeated sickling and ongoing haemolytic anaemia, even when subclinical, lead to parenchymal injury and chronic organ damage, causing substantial morbidity and early mortality. Currently available treatments are limited to transfusions and hydroxycarbamide, although stem cell transplantation might be a potentially curative therapy. Several new therapeutic options are in development, including gene therapy and gene editing. Recent advances include systematic universal screening for stroke risk, improved management of iron overload using oral chelators and non-invasive MRI measurements, and point-of-care diagnostic devices. Controversies include the role of haemolysis in sickle cell disease pathophysiology, optimal management of pregnancy, and strategies to prevent cerebrovascular disease.
Since cricoid pressure was introduced into clinical practice, controversial issues have arisen, including necessity, effectiveness in preventing aspiration, quantifying the cricoid force, and its reliability in certain clinical entities and in the presence of gastric tubes. Cricoid pressure-associated complications have also been alleged, such as airway obstruction leading to interference with manual ventilation, laryngeal visualization, tracheal intubation, placement of supraglottic devices, and relaxation of the lower esophageal sphincter. This review synthesizes available information to identify, address, and attempt to resolve the controversies related to cricoid pressure. The effective use of cricoid pressure requires that the applied force is sufficient to occlude the esophageal entrance while avoiding airway-related complications. Most of these complications are caused by excessive or inadequate force or by misapplication of cricoid pressure. Because a simple-to-use and reliable cricoid pressure device is not commercially available, regular training of personnel, using technology-enhanced cricoid pressure simulation, is required. The current status of cricoid pressure and objectives for future cricoid pressure-related research are also discussed.
Thousands of infants and children undergo complicated surgical procedures that require prolonged periods of anesthesia and/or sedation each year. A growing body of preclinical research suggests pediatric anesthetics are harmful to the developing brain; yet, the extent to which these effects generalize to the clinical setting remains unclear. As there will be a continuing need for surgical and other interventions requiring sedation and/or anesthesia during the neonatal period, it seems clear that research efforts should focus on determining the extent to which general anesthetics can affect the developing brain as well as determining strategies for preventing or ameliorating the adverse effects associated with exposure to such agents. The purpose of this paper is to provide a review of the preclinical literature examining the effects of general anesthesia on brain and behavioral development. This paper will detail the effects of different anesthetic agents on various indices of neurotoxicity and functional outcomes as well as provide a review of potential protective compounds and suggestions for areas of future research.
Background:
Bilateral myringotomy and pressure equalization tube insertion (BMT) is the most common surgery in children. Multiple anesthetic techniques for BMT have been proposed, but that which reliably promotes ideal recovery remains unclear. We sought to assess associations between anesthetic regimens that included single-agent (fentanyl or ketorolac) or dual-agent (fentanyl and ketorolac) analgesic therapy and the primary outcome of maximal postanesthesia care unit (PACU) pain score. Secondary outcomes included in-hospital rescue analgesic administration, recovery time, and emesis incidence.
Methods:
Principal analysis was conducted on a retrospective cohort of 3669 children aged 6 months to <7 years who underwent BMT over a 16-month period and received intraoperative fentanyl and/or ketorolac. Routine anesthetic care included preoperative oral midazolam, general anesthesia via a mask maintained with sevoflurane and N2O or air in O2, and intramuscular analgesic administration. Multivariable analyses were performed examining relationships between analgesic regimen with the following outcomes: maximum PACU Face, Legs, Activity, Cry, and Consolability (FLACC) score = 0 or 7 to 10, oxycodone administration, and time to discharge readiness. Demographic variables, midazolam exposure, and location (main hospital vs ambulatory surgery center) were included in the multivariable analyses as potential confounders. Associations with postoperative vomiting were studied separately in 2725 children from a subsequent, nonoverlapping 12-month period using similar inclusion criteria. Fentanyl and ketorolac dose-response relationships were evaluated for selected outcome variables.
Results:
Maximum FLACC = 0, maximum FLACC score of 7 to 10, and oxycodone rescue were most strongly associated with dual-agent therapy versus single-agent ketorolac: odds ratios 4.89 (95% confidence interval [CI], 4.04-5.93), 0.13 (95% CI, 0.10-0.16), and 0.11 (98.3% CI, 0.09-0.14), respectively, P < .001 for each). Minor associations were found for age, Hispanic ethnicity, midazolam, and location, and none for sex or race. For subjects managed with higher dose fentanyl (≥1.5 µg/kg) and ketorolac (≥0.75 mg/kg), 90% had no demonstrable pain, agitation, or distress. Mean discharge readiness times were 21 ± 11 minutes (ketorolac), 26 ± 16 minutes (fentanyl), and 24 ± 14 minutes (dual) (P < .0001). Postoperative emesis incidences associated with ketorolac (2.7%) versus dual therapy (4.5%) were not different (P = .08).
Conclusions:
In this large retrospective pediatric BMT study, combination intramuscular fentanyl/ketorolac was strongly associated with superior PACU analgesia and reduced need for oxycodone rescue without clinically significant increases in recovery time or emesis incidence. Combination fentanyl at 1.5 to 2 µg/kg and 1 mg/kg ketorolac was associated with optimal outcomes. Dual therapy appears similarly effective in children of either European Caucasian or African ancestry or of Hispanic ethnicity.
Anesthetics permit surgical procedures and stressful interventions have been found to cause structural brain abnormalities and functional impairment in immature animals, generating extensive concerns among clinicians, parents, and government regulators regarding the safe use of these drugs in young children. Critically important questions remain, such as the exact age at which the developing brain is most vulnerable to the effects of anesthetic exposure, whether a particular age exists beyond which anesthetics are devoid of long-term effects on the brain, and whether any specific exposure duration exists that does not lead to deleterious effects. Accordingly, the present analysis attempts to put the growing body of animal studies, which we identified to include > 440 laboratory studies to date, into a translational context, by integrating the preclinical data on brain structure and function with clinical results attained from human neurocognitive studies, which currently exceed 30 studies. Our analysis demonstrated no clear exposure duration threshold below which no structural injury or subsequent cognitive abnormalities occurred. Animal data did not clearly identify a specific age beyond which anesthetic exposure did not cause any structural or functional abnormalities. Several potential mitigating strategies were found, however, no general anesthetic was identified that consistently lacked neurodegenerative properties and could be recommended over other anesthetics. It therefore is imperative, to expand efforts to devise safer anesthetic techniques and mitigating strategies, even before long-term alterations in brain development are unequivocally confirmed to occur in millions of young children undergoing anesthesia every year.
Study objective:
Children with congenital or acquired heart disease have an increased risk of anesthesia related morbidity and mortality. The child's anesthetic risk is related to the severity of their underlying cardiac disease, associated comorbidities, and surgical procedure. The goal of this project was to determine the ease of use of a preoperative risk stratification tool for assigning pediatric cardiac staff and to determine the relative frequency that children with low, moderate, and high risk cardiac disease present for non-cardiac surgery at a tertiary pediatric hospital.
Design:
A risk-stratification tool was prospectively applied to children with congenital heart disease who presented for non-cardiac surgery.
Setting:
Perioperative.
Patients:
We identified a subset of 100 children with congenital heart disease out of 2200 children who required general anesthesia for surgical or radiological procedures over a 6 week period.
Interventions:
A risk stratification tool was utilized to place the patient into low, moderate, or high risk categories to help predict anticipated anesthetic risk. Each grouping specified assignment of staff caring for the patient, clarified preoperative expectations for cardiac assessment, and determined if patient care could be performed at our freestanding ambulatory surgical center.
Measurements:
Electronic perioperative records were reviewed to obtain demographic information, the underlying heart disease, prior cardiac surgery, associated conditions, anesthetic management, complications, and provider type.
Main results:
Approximately 4.5% of children presented with cardiac disease over a 6 week period. In 100 consecutive children with cardiac disease, 23 of the children were classified as low risk, 66 patients were classified as moderate risk, and 11 of the patients were classified as high risk. Pediatric cardiac anesthesiologists provided care to all high risk patients. There were no serious adverse events.
Conclusions:
We found this risk stratification method an effective method to differentiate children into low, moderate, and high risk categories for anesthesia planning and management.
Background:
Dexmedetomidine (DEX) has inherent neuroprotective properties that have been attributed to the activation of prosurvival kinases. However, the impact of supraclinical doses of DEX on neuroapoptosis and neuronal viability has not been determined.
Methods:
Rat pups and primary neuronal cells were treated with DEX or ketamine (KET) alone or in combination. Neuroapoptosis was measured by cleaved-caspase-3 expression and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining in brain sections. Expression of prosurvival kinases was measured by Western blot. We measured the impact of DEX with and without α1-adrenergic receptor blockade on the viability of primary neuronal cell cultures.
Results:
Increasing the cumulative dose of DEX resulted in elevated levels of neuroapoptosis in vivo. Low doses increased, whereas high dose decreased phosphorylation of the prosurvival kinases. KET alone and in combination with DEX produced a greater degree of apoptosis and reductions in expression of these protein kinases than DEX alone. Increasing concentrations of DEX decreased, while coadministration of an α1-adrenergic receptor blocker preserved neuronal viability in vitro.
Conclusions:
Although DEX is neuroprotective at clinical doses, high cumulative doses and concentrations induce neuroapoptosis, in vivo and in vitro, respectively. Because the current dosing schedules used in humans yield plasma levels that are substantially below concentrations that induce neurotoxicity, low-dose DEX should not be neurotoxic and has the potential to be a neuroprotective adjuvant.
Background:
Animal studies demonstrate general anesthetic (GA) toxicity in the developing brain. Clinical reports raise concern, but the risk of GA exposure to neurodevelopment in children remains uncertain.
Methods:
The authors undertook a retrospective matched cohort study comparing children less than 4 yr of age exposed to GA to those with no GA exposure. The authors used the Early Development Instrument (EDI), a 104-component questionnaire, encompassing five developmental domains, completed in kindergarten as the outcome measure. Mixed-effect logistic regression models generated EDI estimates for single versus multiple GA exposure and compared both single and multiple exposures by the age of 0 to 2 or 2 to 4 yr. Known sociodemographic and physical confounders were incorporated as covariates in the models.
Results:
A total of 18,056 children were studied: 3,850 exposed to a single GA and 620 exposed to two or more GA, who were matched to 13,586 nonexposed children. In children less than 2 yr of age, there was no independent association between single or multiple GA exposure and EDI results. Paradoxically, single exposure between 2 and 4 yr of age was associated with deficits, most significant for communication/general knowledge (estimate, -0.7; 95% CI, -0.93 to -0.47; P < 0.0001) and language/cognition (estimate, -0.34; 95% CI, -0.52 to -0.16; P < 0.0001) domains. Multiple GA exposure at the age of 2 to 4 yr did not confer greater risk than single GA exposure.
Conclusions:
These findings refute the assumption that the earlier the GA exposure in children, the greater the likelihood of long-term neurocognitive risk. The authors cannot confirm an association between multiple GA exposure and increased risk of neurocognitive impairment, increasing the probability of confounding to explain the results.
Objectives/hypothesis:
The purpose of this investigation was to assess current drug-induced sleep endoscopy (DISE) practice patterns at centers that have published on the technique, to identify areas of agreement, and to identify areas of disagreement that may represent opportunities for improvement and standardization.
Study design:
Multi-institutional survey.
Methods:
A survey was designed in two phases to evaluate preoperative assessment, intraoperative performance, and postoperative management of patients undergoing DISE. The survey was constructed iteratively in consultation with the all of the coauthors, each selected as an expert owing to their previous publication of one or more articles pertaining to pediatric DISE. In the first phase of survey creation, each expert was asked to provide narrative answers to questions pertaining to DISE. These responses served as the basis for a second survey. This second survey was then administered to all pediatric otolaryngologists at each respective institution.
Results:
Overall, there was a low rate of agreement (33%) among the respondents; however, there was substantial agreement within institution, particularly for the use of anesthetic medications, the use of cine magnetic resonance imaging, and performance of bronchoscopy along with DISE. There was strong agreement among all respondents for performing DISE in a child with severe obstructive sleep apnea following adenotonsillectomy, regardless of comorbidities.
Conclusion:
This multi-institutional survey demonstrated a lack of consensus between experts and multiple opportunities for improvement. In general, there was agreement regarding the workup prior to DISE performance and the endoscopic protocol but disagreement regarding anesthetic protocol and management decisions.
Level of evidence:
4. Laryngoscope, 2016.
Background:
In pediatric anesthesia, preoperative fasting guidelines are still often exceeded.
Objective:
The objective of this noninterventional clinical observational cohort study was to evaluate the effect of an optimized preoperative fasting management (OPT) on glucose concentration, ketone bodies, acid-base balance, and change in mean arterial blood pressure (MAP) during induction of anesthesia in children.
Methods:
Children aged 0-36 months scheduled for elective surgery with OPT (n = 50) were compared with peers studied before optimizing preoperative fasting time (OLD) (n = 50) who were matched for weight, age, and height.
Results:
In children with OPT (n = 50), mean fasting time (6.0 ± 1.9 h vs 8.5 ± 3.5 h, P < 0.001), deviation from guideline (ΔGL) (1.2 ± 1.4 h vs 3.7 ± 3.1 h, P < 0.001, ΔGL>2 h 8% vs 70%), ketone bodies (0.2 ± 0.2 mmol·l(-1) vs 0.6 ± 0.6 mmol·l(-1) , P < 0.001), and incidence of hypotension (MAP <40 mmHg, 0 vs 5, P = 0.022) were statistically significantly lower and MAP after induction was statistically significantly higher (55.2 ± 9.5 mmHg vs 50.3 ± 9.8 mmHg, P = 0.015) as compared to children in the OLD (n = 50) group. Glucose, lactate, bicarbonate, base excess, and anion gap did not significantly differ.
Conclusion:
Optimized fasting times improve the metabolic and hemodynamic condition during induction of anesthesia in children younger than 36 months of age.
Importance
Exposure of young animals to commonly used anesthetics causes neurotoxicity including impaired neurocognitive function and abnormal behavior. The potential neurocognitive and behavioral effects of anesthesia exposure in young children are thus important to understand.
Objective
To examine if a single anesthesia exposure in otherwise healthy young children was associated with impaired neurocognitive development and abnormal behavior in later childhood.
Design, Setting, and Participants
Sibling-matched cohort study conducted between May 2009 and April 2015 at 4 university-based US pediatric tertiary care hospitals. The study cohort included sibling pairs within 36 months in age and currently 8 to 15 years old. The exposed siblings were healthy at surgery/anesthesia. Neurocognitive and behavior outcomes were prospectively assessed with retrospectively documented anesthesia exposure data.
Exposures
A single exposure to general anesthesia during inguinal hernia surgery in the exposed sibling and no anesthesia exposure in the unexposed sibling, before age 36 months.
Main Outcomes and Measures
The primary outcome was global cognitive function (IQ). Secondary outcomes included domain-specific neurocognitive functions and behavior. A detailed neuropsychological battery assessed IQ and domain-specific neurocognitive functions. Parents completed validated, standardized reports of behavior.
Results
Among the 105 sibling pairs, the exposed siblings (mean age, 17.3 months at surgery/anesthesia; 9.5% female) and the unexposed siblings (44% female) had IQ testing at mean ages of 10.6 and 10.9 years, respectively. All exposed children received inhaled anesthetic agents, and anesthesia duration ranged from 20 to 240 minutes, with a median duration of 80 minutes. Mean IQ scores between exposed siblings (scores: full scale = 111; performance = 108; verbal = 111) and unexposed siblings (scores: full scale = 111; performance = 107; verbal = 111) were not statistically significantly different. Differences in mean IQ scores between sibling pairs were: full scale = −0.2 (95% CI, −2.6 to 2.9); performance = 0.5 (95% CI, −2.7 to 3.7); and verbal = −0.5 (95% CI, −3.2 to 2.2). No statistically significant differences in mean scores were found between sibling pairs in memory/learning, motor/processing speed, visuospatial function, attention, executive function, language, or behavior.
Conclusions and Relevance
Among healthy children with a single anesthesia exposure before age 36 months, compared with healthy siblings with no anesthesia exposure, there were no statistically significant differences in IQ scores in later childhood. Further study of repeated exposure, prolonged exposure, and vulnerable subgroups is needed.
