Abstract
Annually in the UK, around half a million children and infants undergo general anaesthesia. The provision of anaesthesia for this patient group can be a daunting task; the size of the patient is very variable, disease states and pathology are present that are not seen in other areas of practice, and there are substantial challenges of communicating and allaying anxiety. Additionally, unique medicolegal concepts exist. As those charged with the patients care during unique situations, it is important for anaesthetists to have a holistic understanding of the treatment they will be providing.
We have sought to consolidate the key areas of practice into core principles that can be applied to neonates, infants and children, to allow the reader insight into the foundations of safe paediatric anaesthetic conduct. Key important differences in these patient groups are outlined, including anatomy, drug handling and fluid requirements. Essential concepts of preoperative assessment and management of the anxious child are included, to provide colleagues with the tools for identification and management of challenging scenarios.
After reading this article, you should be able to:
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understanding how size changes with age, using simple formulae, and its significance in clinical setting
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appreciate the anatomical and physiological differences between adults and children, including understanding how this relates to anaesthesia
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have a basic understanding of metabolism in children and its variations with maturation and differing body habitus of a child.
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understand the medicolegal aspects of providing anaesthetic care to children and strategies to deal with an uncooperative child
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have an overview of preoperative assessment and preparation for surgery
Calculating the ‘Corrected age’
Current age (weeks) + gestation age at birth (weeks)
Example: Baby born at 32 weeks, now 4 weeks after birth. What is the corrected age?
4 weeks + 32 weeks = Corrected age 36 weeks
Gestational adjusted age
40 – Gestational age in weeks = X
Gestational adjusted age = Current age (weeks) – X
Example: Child born at 28 weeks’ gestation. Current age is 18 weeks. What is the adjusted gestational age.
X = 40–28 = 12 weeks
Current age = 18 weeks
Gestational adjusted age = 18–12 = 6 weeks
Calculations and normograms
Measurement of basic parameters such as weight and height in a child can be challenging. Clinicians may need to treat children in their care without actual measurements.
Below are basic formulae useful for approximating key parameters:
There are various formulae for weight calculation.
Weight estimation based on age of child:
| Advanced Paediatric Life Support (APLS) formulae | |
| Ages 0–12 months | Age (months) x 0.5 + 4 |
| Ages between 1 and 5 years | Age (years) x 2 + 8 |
| Ages 7–10 years | Age x 3 + 2 kg |
| Luscombe–Owens formula | (Age x 3) + 7 |
| Erker’s formulae based on body habitus | |
| Weight = (2 x age) + 6 | Tall and thin children |
| Weight = (3 x age) + 6 | Normal children |
| Weight = (4 x age) + 6 | Tiny and thick children |
| Estimation of height of a child: | |
| Height | Age (years) x 6.5 + 76 cm |
| Based on birth weights (BW) | BW x 2 at 3.5 years |
| BW x 3 at 12 years | |
Introduction
Children are diverse, changing beings, and providing anaesthesia for them requires an understanding of these changes. In addition to body size there are other physiological changes ( Table 1 ). This presents anaesthetists with challenges not seen in other areas of practice, and not limited to the anaesthetic room or operating theatre. It is often stated that ‘children are not small adults’. Whilst true, care should be taken in interpreting this. Children are also not large neonates. The rate of development is never as rapid as during the first days and then weeks of life and, other than size, a 1-year-old child has more in common physiologically with an 18-year-old than a 1-day-old. Many of the differences emphasized are applicable only to small infants but other will apply also to older children. Understanding the impact of development on the care we provide is part of the science, the craft, and the ‘art’ of paediatric anaesthesia.
| Body system | Sub-system | Anatomy and physiology | Anaesthetic implications |
|---|---|---|---|
| Respiratory system | Airway | Large head Small mouth Easily compressible tissues Relatively large, flat tongue Long, narrow epiglottis Anterior larynx Slanting, shorter vocal cords Sub-glottic area is narrowest Fragile mucosa easily damaged by ETT | Upper airway obstruction
|
| Lungs | Tracheal length variable Bronchial division equal Compliant chest wall Horizontal rib cage Weak intercostal muscles Diaphragmatic breathing | Endobronchial intubation can be right or left bronchus Lack of bucket-handle movement Easily fatigued respiratory muscles Obligatory nasal breathers | |
| Cardiovascular system | Heart and blood vessels | Fetal circulation and vessels
Higher Hb concentration Higher HR during younger ages Higher CO than adults Veins smaller diameter and subcutaneous fat Small blood volume | Translational circulation due to raised PVR CO more dependant on HR, therefore bradycardia poorly tolerated Umbilical venous and arterial lines Predominant parasympathetic tone. Bradycardia during intubation. Persistent intracardiac shunts risks of paradoxical embolus Difficult venous access |
| Central nervous system | Brain & Spinal cord | Brain size at birth is 25% but 90% at 6 years. Open fontanelles
Fragile blood vessels in brain Spinal cord at various levels based on age
| MAC requirement is low in premature babies and neonates MAC is 1.5 times more in toddlers Large head in infants if raised CSF pressure or volume Fontanelles – sign of volume status Intraventricular haemorrhage in neonates during stressful increases in BP Risk of spinal cord injury due to low lying spinal cord Higher LA dose required for spinal block and short acting |
| Gastrointestinal system | Increased glucose requirement Low glycogen storage Increased insensible fluid loss Higher BMR Cylindrical abdomen Longer intestinal length Lower oesophageal spincher tone reduced (until 12 months) | Risk of hypoglycaemia (especially premature babies) Dehydration risk during illness or poor feeding Organ damage during blunt trauma Reflux risk | |
| Renal system | Greater fluid requirements Sodium wasting due to immature tubular function Water loss (reduced concentration effect) Excretion of drugs slower | Dehydration risk Inability to handle salt IV fluids containing pure water can result in severe water toxicity Longer action of drugs excreted in urine | |
| Other systems | Muscles | Poor muscular tone Poor muscle coordination | Easily fatiguability |
| Bones | Growth plates Soft bones and rapidly maturing Unfused bones | Fractures at growth plates High requirement of calcium and vitamin D (rickets) | |
| Temperature | Higher BSA Increased evaporative loss Lowe metabolism and heat generation Lack of perspiration | Hypothermia susceptibility Careful monitoring and active warming needed to prevent hypothermia Susceptible to hyperthermia if not monitored |
In the article, we aim to give a summary of the key areas of consideration when managing children. The focus is on anatomy, physiology, and pharmacology as well as the specific medicolegal concepts encountered. Practical advice on premedication and management of perioperative anxiety is included. Induction of anaesthesia may be the most stressful part of the child’s perioperative journey from the perspective of the child and their family, empathy and understanding of the phycological and social aspects of this is important.
Drug metabolism in children and significance
Drug distribution
Distribution of a drug is influenced by both drug and patient factors:
Drug factors: drug absorption is dependent upon the state of the drug as it is presented at a membrane. Highly lipid soluble, non-ionized molecules will easily cross membranes, including the blood–brain barrier. Protein binding is also important; highly protein bound drugs have a smaller free fraction available – it is this free fraction that exerts the clinical effect.
Patient factors: the body composition of the patient is the most crucial factor in determining drug distribution. The total body water and degree of protein binding are a direct function of this composition. For example, the total body water in the premature neonate may be as high as 85%, reducing to 60% by one year of life. Further details are outlined below ( Table 2 ).
| Age | Premature neonate | Neonate | 1 year old | Adult (male) |
|---|---|---|---|---|
| Total body water (%) | 85 | 80 | 60 | 60 |
| Intracellular water (%) | 25 | 35 | 35 | 40 |
| Extracellular water (%) | 60 | 45 | 25 | 20 |
The implication of this is that water-soluble drugs will have a greater volume of distribution in the neonate, resulting in them needing a higher-than-expected dose for clinical effect. This theoretical prediction does not often translate directly to clinical anaesthetic practice – neonates are extremely sensitive to medications affecting the cardiovascular system, respiratory systems, and the neuromuscular junction, as these systems are often underdeveloped and sensitive to drug actions.
Muscle and fat: many anaesthetic drugs, such as induction agents, redistribute quickly to muscle and fat. This can result in a prolonged duration of action, e.g. propofol in the neonate due to virtually non existent fat stores.
Protein binding: the two primary drug binding proteins are albumin and α-1-acid glycoprotein (AAGP). The amount of protein available for binding changes dramatically in the first 6 months of life.
In both prematurity and at birth, there are lower concentrations of albumin and AAGP. Thus, the free fraction of drugs typically expected to be protein bound will increase, resulting in a larger than expected clinical effect (e.g. diazepam, bupivacaine, barbiturates).
Blood–brain barrier: the blood–brain barrier in the neonate is underdeveloped. Lipid-insoluble drugs may reach the central nervous system (CNS) more easily, as well as drugs that would typically have poor CNS penetrance, e.g. antibiotic regimens typically ineffective in older children are recommended for neonates, active metabolites of drugs such as ketamine more readily cross the blood–brain barrier.
Metabolism
Drug metabolism is dependent upon hepatic blood flow and enzyme maturity. Neonatal hepatic blood flow is reduced compared to that of a child, increasing as a proportion of the cardiac output as the infant matures. The enzyme families involved in the majority of anaesthetic drug metabolism (cytochrome p450 superfamilies) mature at different rates: thus, all drugs used within the perioperative period are titrated to effect, or to measured drug levels where available.
Excretion
Most drugs are excreted renally. Renal function in the neonate is markedly reduced compared to the older child and adult. Glomerular filtration rate does not reach maturity until 2 years of age, with only around 15% function at birth. This is due to several factors including reduced osmotic load, low renal perfusion pressure and incomplete glomerular development.
Individual drugs/drug groups
As outlined above, there are a myriad of factors that influence the clinical effect of administered drugs. Below are some general rules for commonly used agents.
Inhalational agents undergo minimal metabolism and are excreted unchanged. Minimum alveolar concentration (MAC) values vary with age, with a trough in the neonatal period followed be a peak at 6–12 months of age before declining to adult values by age 10.
Propofol: rapidly redistributed due to the proportionally higher cardiac output for any given bodyweight, even when used in neonates. Elimination is reduced in neonates and this may lead to accumulation if not accounted for.
Ketamine: ketamine is extensively metabolized by the p450 cytochrome complex, particularly CYP3A4. CYP3A4 is immature in the neonate, but activity rises markedly in infancy and is greater than that of adults. The metabolite, nor-ketamine is active and has 20–30% the potency of ketamine. The overall effect is higher than expected dose range for children.
Midazolam is cleared hepatically. In contrast to ketamine hepatic blood flow is more important that the maturity of the enzyme system (CYP3A4) and half-life is prolonged due to reduced hepatic blood flow in neonates. The metabolites of midazolam are not active, making it useful for shorter procedures.
Neuromuscular blockers have an exceptionally low volume of distribution, primarily due their nature as large, ionized molecules. Children compared to adults have a relatively increased volume of extracellular fluid. This translates to needing a larger first dose for clinical effect. For example a dose of 2 mg/kg of suxamethonium, is required for a rapid sequence intubation (RSI).
Nutrition and obesity
Rates of obesity among children have risen over the last 50 years. Body mass index (BMI) is a simple indicator of the nutritional status of a child.
BMI=Weight(kg)/Height(metres)2
Normograms differ for boys and girls. BMI are plotted on centile chart which demonstrate variation as well as expected values.
Obesity is usually defined by reference of BMI to centiles. Various definitions exists but a useful classification is:
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BMI over 91st centile is overweight
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BMI over 98th centile is very overweight (clinically obese)
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BMI over 99th centile is severely obese
Prescribing for children living with obesity is a complex issue. The handling of drugs can vary significantly, and research into this topic is an evolving field. The Society for Bariatric Anaesthesia (SOBA) has released its first guidance aimed at this topic, accessible here https://www.sobauk.co.uk/ .
Whilst there has been increasing focus on obesity, underweight children (BMI of less than 0.4th centile) also form an important and vulnerable group. Low body weight can be a sign of severe health issues. A larger group of children, with BMI less than 9th centile, are considered higher risk for perioperative complications.
World Health Organization growth charts for weight/height and BMI are available to download:
Fluids and electrolytes
Fluid requirements and composition varies by age and pathology. This section contains recommendations from the UK National Institute for Health and Care Excellence (NICE).
Neonates
Routine maintenance IV fluid rates for term neonates varies according to age. The following is a guide:
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From birth to day 1: 50–60 ml/kg/day.
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Day 2: 70–80 ml/kg/day.
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Day 3: 80–100 ml/kg/day.
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Day 4: 100–120 ml/kg/day.
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Days 5–28: 120–150 ml/kg/day.
Older children
Maintenance fluid rates for children and young people is calculated using the ‘Holliday–Segar formula’ (100 ml/kg/day for the first 10 kg of weight, 50 ml/kg/day for the next 10 kg and 20 ml/kg/day for the weight over 20 kg).
Alternatively; hourly maintenance rates can be calculated using 4-2-1 formula.
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4 ml/kg/hour for first 10 kg
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2 ml/kg/hour for 10–20 kg
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1 ml/kg/hour for each kg over 20 kg
Be aware that over a 24-hour period, males rarely need more than 2500 ml and females rarely need more than 2000 ml of fluids.
Glucose supplementation
The need for routine glucose supplement supplementation varies by age group. Outside of the immediate neonatal period, routine glucose supplementation is usually not needed. The stress response to surgery often causes a rise in blood glucose.
Specific patient populations requiring glucose supplementation include those with underlying metabolic disease, hepatic pathology, and children below the 5th centile of bodyweight or when intravenous glucose administration (or TPN) was in place prior to surgery. This list is not exhaustive. Glucose concentration should be monitored in patients at risk.
Neonates
Hypoglycaemia is common in neonates, and routine glucose supplementation is required. Prolonged exposure to blood glucose levels below 2.6 mmol/litre are associated with adverse neurological outcomes.
The rate of glucose infusion for term neonates should be in the range of 4–6 mg/kg/minute
The rate of glucose infusion for premature neonates should be in the range 6–8 mg/kg/minute
Practically, this can be delivered as a secondary infusion of 10% glucose (100 mg/ml) running in conjunction with maintenance fluid. Other methods of glucose delivery vary by organization. To calculate the glucose infusion rate, the following can be used, irrespective of the glucose concentration.
Glucoseinfusionrate(mg/kg/minute)=Rate(ml/hour)×%glucoseWeight(kg)×6
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