Paediatric analgesia and pain assessment

Cite this article as:
Ciara Murphy. Paediatric analgesia and pain assessment, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.23666

Jamie is a 3-year-old boy who presents to the emergency department. He was playing with his 5-year-old brother on the trampoline and fell off. He is very distressed and crying in triage but his mum doesn’t know where he hurt himself. She had rushed to the department with him and so hadn’t given him any prehospital analgesia. Mum herself also appears very anxious and worried.

 

Pain assessment and management in the paediatric population is a challenging area, and it is something that we often get wrong.   Children’s pain is historically poorly measured and often undertreated because children may not exhibit the common signs and symptoms of pain that we come to expect from adults.

Pain is multifactorial. In children, it is important to not just focus on the injury but the age and developmental stage of the child, the circumstances of the presentation to ED, the behavior of the parent/caregiver and the child’s interaction with them.

In the case of James, his mum appears very anxious about his injury. Children tend to feed off of their parent’s anxiety and become more distressed. Moving them to a quiet area for assessment and reassuring mum that they are in the right place and that you’re going to take great care of James is an ideal starting point. Hopefully, reassuring and calming his mum will go some way to diffusing the situation, and calming James also.

 

Pain assessment

Assessment of a child in pain varies greatly with their age and developmental stage. This is one of the most important things to take into account during your encounter. If the wrong tool is used, the pain may be underestimated and the child under-treated. The longer the time to proper pain relief, the more distress there is for both child and parent, and so the spiral continues.

 

Neonates and infants (0 – 2 years)

For the youngest, the FLACC (Faces, Legs, Arms, Cry, Consolability) scale can be useful. This scale comprises of five components. The child needs to be observed for at least a minute. A child of this age isn’t going to be able to tell you much about their pain, so you need to rely heavily on your observational skills. Involving the parent in the assessment is  key.

Context is very important in this group also, particularly for the one-year-old who seems very distressed in triage or when being examined by the strange doctor but is more settled in mum’s lap. Frequent reassessments are therefore extremely important and beneficial.

 

Toddlers and preschoolers (2 – 4 years)

In this group, developing a rapport is a must in order to be able to accurately assess the level of pain. Get on the child’s level, use a soothing friendly voice, employ some ice-breaking chat.

Ask open-ended questions, don’t just palpate areas and say “Does this hurt?” – as you may well get a yes in every area – e.g. “Can you show me where is sore? Can you point to what is hurting you?

For these slightly older children, the Wong-Baker faces scale is great. These can be produced in bright colours to make them fun  and to aid with their participation in the assessment.

 

 

This scale has been validated in children aged 3 and up, but in practice it is often used in those over 2. The child is shown the faces and asked to point to the one that best represents how they are feeling.

Again, reassessment after initial analgesia using the same scale/method of assessment is important.

 

School-aged children (4 – 16 years)

As the child develops verbally, the assessment of their pain should become easier. For children aged 4-8  years of age, the Wong-Baker faces scale is probably still the most appropriate tool to use. In the older child, you can use the numerical pain ladder.

This can be either a visual representation where you ask them to draw a line or indicate where their pain falls on a physical scale, or you can simply ask them to give their pain a score out of 10 without showing them the scale.

 

 

You move James and his mum to the minors area to complete his assessment. Mum is now calmer, and this seems to have settled James somewhat. He is no longer crying, but he is still grimacing and he appears to be holding his left elbow fixed in flexion. You ask him point to where it is sore and he indicates his left arm. He refuses to move it. A survey of the rest of his body doesn’t reveal anything else concerning, he is fully weight-bearing and is moving his neck and right arm without issue. On palpation and careful examination of the left arm he is very distressed when his elbow is touched, and it appears to be swollen. You show him the Wong-Baker scale and he points to the orange sad face, which indicates a pain score of 8.

 

Pain management

To achieve the best pain management for our patients, we first have to have a basic grasp of pain physiology.

Nocioceptive pain follows a sequence where 4 events take place:

Pain transduction – a painful stimulus eg trauma causes tissue damage – this leads to the release of chemical mediators in the tissue, e.g. prostaglandins/substance P etc. These trigger an action potential.

Transmission – the action potential moves along the nerve fibres, travelling from the peripheral site of injury to the spinal cord.

Perception – the action potential travels along the spinothalamic tract to the brain, where it is relayed to the areas involved in pain perception (limbic system, somatosensory cortex, parietal and frontal lobes)

Modulation – the midbrain releases endorphins/serotonin etc to mitigate pain

We can target each part of the sequence in our treatment of pain, as long as we remember that analgesia is multi-modal, and does not just revolve around drugs.

 

 

Transduction

We can intervene at this stage by employing basic first aid measures – for example

  • If the child has a burn – run it under cool/room temperature water. This will provide pain relief as well as arresting further tissue damage
  • If a limb is obviously deformed or clinically has a fracture – splint or backslab the limb during your initial assessment and before sending the child for x-rays
  • If there is a suspicion of a clavicular or shoulder injury give the child a sling
  • If they have a swollen area ?soft tissue injury e.g. ankle – place an ice pack and get them to elevate the ankle.

These things may seem like common sense, but all too often they are forgotten in favour of pharmacological interventions which will not have as immediate an effect.

 

Perception

A child can be distracted much more easily than an adult, and we need to use this to our advantage in the context of pain management. Employing distraction techniques can affect and reduce a child’s perception of pain.

There are many options available and you can get the parents involved also. Distraction techniques obviously vary in their effectiveness depending on the age of the child, but they include: story-telling; singing a song (I can’t be the only one that hears Baby Shark as they fall asleep at this point!); balloons; stickers; bubbles; playing a video on a smartphone.

For older children, guided imagination can be used to great effect, particularly before procedural sedation with nitrous oxide or ketamine. Letting them listen to their own music on their phone via earphones is also a good idea. Some departments are now looking at the role of virtual reality headsets for older children undergoing painful procedures which appears to be a very successful method of distraction.

 

Transmission

Pharmacological agents act to interrupt the transmission of the painful stimulus. There are many agents available, depending on the child’s age and the level of pain described.

Topical anesthetics

Ametop (4% w/w Tetracaine) and EMLA 5% (lidocaine/prilocaine) are anaesthetic creams that can be applied to intact skin, usually pre-cannulation. They numb the skin and make the procedure less painful. They are ideal in situations where a slight delay to cannulation is safe, as they need to be in situ for a while to work (Ametop 30 mins, EMLA for an hour).

LAT gel – Lignocaine 4% / Tetracaine 0.5% / Adrenaline 0.1% is an anaesthetic gel. It comes in a single-use bottle. It is designed for use on broken skin, and so it should be ideally applied to wounds/lacerations in triage and left in situ for 30. It numbs the area and allows for thorough cleaning, proper assessment, and closure of wounds while reducing the need for injectable local anaesthetic in a lot of cases.

Contraindications

  • ANY previous reaction to local/ general anaesthetic or known cholinesterase deficiency
  • Wound on or near mucus membrane including eye, nose or mouth.
  • Wound > 5 cm in length
  • Concern about tissue viability i.e. crush or flap wounds
  • Wounds over 8 hours old
  • Obvious injury to associated structures i.e. bone, tendon, blood vessels, joint or nerve
  • Wounds to the ear, nose, genitalia or digits should be discussed with a registrar before using LAT gel. This is due to concerns about perfusion and also due to evidence showing less effect on extremity wounds.

 

Paracetamol

This is perhaps best known to parents as Calpol (UK and Ireland), Panadol or Crocin (Australia) or Tylenol (in the States), however, there are other brand names. There are two different preparations of Calpol depending on age (120mg/ 5mls or 250mg/5mls) so make sure to clarify what the parent has at home.

Paracetamol can be given PO/PR/IV but is most commonly given orally. The dose is 15mg/kg to a maximum dose of 1 g.

It can be given 4-6 hourly, but to a maximum of 4 doses in 24 hours. It takes approximately 30 minutes to work

Overdose is 75mg/kg (although toxicity usually doesn’t occur until >150mg/kg in an acute ingestion or repeated supra therapeutic doses>100mg/kg). If this happens it can cause hepatic necrosis – so bloods will need to be checked and if the paracetamol level is beyond a certain threshold the child will need to be started on n-acetyl cysteine.

 

Ibuprofen

Ibuprofen is a non-steroidal anti-inflammatory (NSAID) that is available over the counter. NSAIDs work to stop the inflammatory cascade of chemical mediators and thus reduce inflammation and pain. It is also an anti-pyretic.

It is commonly sold as Nurofen (in the UK, Ireland and Australia) and Advil (in America) but again has other brand names as well as being sold by generic name. Nurofen also comes in two preparations (100mg/5mls or 200mg/5mls) – always clarify with the parents as to what they have at home to ensure appropriate dosing.

Ibuprofen can be given at a dose of 10mg/kg to a max of 400mg 8 hourly. An overdose obviously isn’t desirable but does not carry the same dangers as paracetamol.

It can be given PO or PR, however the suppositories only come in 60mg so are not as useful in bigger children.

Always, always double-check which medicine a parent may have given at home. For example, Calpol contains paracetamol but Calprofen contains ibuprofen – you can see how double doses can accidentally be given in the emergency department soon after a child presents.

 

Diclofenac

Diclofenac also a member of the NSAID family. It can be used in place of ibuprofen in the older child in its oral form.

In my own practice PR diclofenac suppositories have been invaluable in the pain management of infants with stomatitis or bad tonsillitis causing distress and poor oral intake, while also controlling their pyrexia.

The dose is 1mg/kg 8 hourly (max 50mg per dose) and can be given PO/PR.

Max dose is 3mg/kg in 24 hours.

 

Morphine

Morphine is a strong natural opioid. It is used for severe pain, or pain that is not responding to first-line analgesics. It can be given by a variety of routes, but most commonly PO or IV.

Oramorph is an oral form of morphine, available in liquid preparation and is dosed by age band:

  • <1 year: 80 -200mcg/kg
  • 1-2 years:200-400mcg/kg
  • 2-12 years:200-500mcg/kg
  • 12-18 years: 10-15mg

Its IV dose is 0.1mg/kg. It can be given prn usually every 4-6 hours

Potentially serious side effects include decreased respiratory effort and low blood pressure. Overdose treatment includes the administration of naloxone (0.1mg/kg IM or IV).

 

Fentanyl

Fentanyl is a strong synthetic opioid with a faster onset / offset than morphine, starts to work within 7 minutes. It’s great for initial analgesia for fractures/dislocations, burns, major lacerations.

The loading dose is 1.5mcg/kg and can be repeated after 20-30 minutes

Side effects are uncommon, but may include respiratory depression/hypotension/nausea and vomiting. It is given intranasally (IN) with an atomizer device and has great mucosal uptake without having the need for IV access.

 

Diamorphine

Diamorphine is also an opioid that can be given intranasally as an alternative to fentanyl, using an atomizer device.

The dose is 0.1mg/kg IN

It carries the same potential side effects as morphine and fentanyl, but has been shown to be very safe at this dose in the paediatric population.

 

Methoxyflurane

Methyoxyflurane is also known as Penthrox / the green whistleIt is an inhaled medication primarily used to improve pain following trauma. Each dose lasts approximately 30 minutes.

Pain relief begins after 6–8 breaths and continues for several minutes after stopping inhalation

It is self-administered to children and adults using a hand-held inhaler device

 

The STOP trial looked at its safety and efficacy in adults and children >12 and found that it was safe and worked well. It is currently being investigated in those aged 6-18 in the MAGPIE trial, which is still undergoing data collection.

 

Procedural sedation

Sometimes, analgesia alone isn’t enough. If a child has a deformed fracture for example that needs to be manipulated, they will need procedural sedation. This is usually achieved with wither nitrous oxide or ketamine, depending on the child’s age and the procedure required.

 

You suspect that Jamie has a fractured arm, perhaps a supracondylar fracture. His weight is 18kg. Given his level of distress and pain score of 8, you give him both IN fentanyl 27mcg and paracetamol 270mg. Mum plays a video on her phone for him while you apply an above elbow backslab to splint and immobilize his arm before he goes to x-ray.

You reassess him after these interventions and he looks much happier, you even get a smile. He indicates the second green face on the Wong-Baker scale, equating with a pain score of 2. He goes for an x-ray which confirms a supracondylar fracture – Gartland 2. 
You refer him to the orthopaedic team for admission and management. You ensure that he has regular analgesics as well as PRN extras written up in his drug Kardex before he leaves the department to go to the ward.

 

References

Srouji R, Ratnapalan S, Schneeweiss. Pain in Children: Assessment and Nonpharmacological Management. International Journal of Pediatrics. 2010. doi:10.1155/2010/474838

https://pemplaybook.org/podcast/pediatric-pain/

Manwarren R and Hynan L. Clinical Validation of FLACC: Preverbal patient pain scale. Pediatric Nursing. 2003; 29(2):140-6

Keck JF et al. Reliability and validity of the Faces and Word Descriptor Scales to measure procedural pain. J Pediatr Nurs. 1996;11(6):368-741996

Tomlinson D et al. A systematic review of faces scales for the self-report of pain intensity in children. Pediatrics. 2010;126(5):e1168-98. doi: 10.1542/peds.2010-1609

Horeczko T. “Acute Pain in Children”. In Management of Pain and Procedural Sedation in Acute Care. Strayer R, Motov S, Nelson L (eds). 2017.  

Knight K, McClenaghan CE, Singh B: Virtual reality distraction from painful procedures in the paediatric emergency departmentArchives of Disease in Childhood 2019;104:204-205.

Leicester Children’s Hospital clinical guideline. Use of Topical Wound Anaesthetic- LAT gel in the PED. Rowlands. Feb 2014.  https://static1.squarespace.com/static/546e1217e4b093626abfbae7/t/59cba0aa12abd9d55c449106/1506517164347/Topical+Wound+Anaesthetic+-+LAT+Gel+UHL+Paediatric+Emergency+Guideline.pdf

Royal Children’s Hospital Melbourne clinical guideline. Management of paediatric paracetamol overdose. https://www.rch.org.au/clinicalguide/guideline_index/Paracetamol_poisoning/

Sharif MR et al. Rectal Diclofenac Versus Rectal Paracetamol: Comparison of Antipyretic Effectiveness in Children. Iran Red Crescent Med J. 2016;18(1): e27932

Kendall J, Maconochie I, Wong ICK, et al; A novel multipatient intranasal diamorphine spray for use in acute pain in children: pharmacovigilance data from an observational study. Emerg Med J 2015;32:269-273.

Coffey F, Wright J, Hartshorn S, et al: STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain. Emerg Med J 2014;31:613-618.

Self-reported pain scales

Cite this article as:
Crystal McLeod. Self-reported pain scales, Don't Forget the Bubbles, 2018. Available at:
https://doi.org/10.31440/DFTB.14701

A 6-year-old boy is brought to the Emergency Department after a fall from a tree. He walks into triage but is holding his arm and grimacing with pain. Immediately, you conduct a focused physical exam of his arm and rule out other injuries. It is obvious to you that this patient is in pain. You would like to assess his experience of pain in more depth. How are you going to do it?

Send in the clowns

Cite this article as:
Andrew Tagg. Send in the clowns, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.9868

Clowns – you either love them or you hate them.  There is no middle ground.  But what do children think about them? Hospitals can be strange, scary places, even in daylight. So some have introduced ‘clown’ doctors to help allay fears. But do they?

(Editor note: If you have *coulrophobia then don’t read this post)

Analgesia and sedation

Cite this article as:
Marc Anders. Analgesia and sedation, Don't Forget the Bubbles, 2013. Available at:
https://doi.org/10.31440/DFTB.3867

Intravenous anaesthetic agents (see table):

  • classified as barbiturates (thiopentone) and non-barbiturates (propofol and ketamine)
  • thiopentone use is largely limited to induction in status epilepticus and for treatment of raised ICP; it has no analgesic properties and is in fact anti-analgesic at sedative doses
  • propofol is suitable for induction (bolus) and maintenance of sedation/anaesthesia (infusion); it is suitable for discrete painful procedures but has only minimal analgesic properties at sedative doses and so must be combined with a suitable analgesic
  • propofol is a direct myocardial depressant and so should be used in caution in patients in (or at risk of) low cardiac-output syndrome (LCOS). It obtunds the normal baroreceptor reflex and so causes a decrease in blood pressure and heart rate
  • ketamine is a dissociative anaesthetic that is also a potent analgesic; it is suitable for discrete painful procedures but increases respiratory secretions and is complicated by psychadelic phenomena (midazolam is suitable to treat or obviate ketamine’s emergence phenomena but will prolong recovery time)
  • combined ketamine and propofol in a ratio ranging from 1:1 to 1:4 (ketofol) is becoming a popular awake-sedative to facilitate medical procedures

Narcotics (see table):

  • morphine, fentanyl and methadone are effective analgesics and sedatives; oxycodone is also a popular analgesic but is less sedating
  • levels of sedation, analgesia and respiratory depression do not correlate (patients may be well sedated and have respiratory depression but not have adequate analgesia)
  • morphine is not a suitable narcotic for discrete painful procedures due to its long and unpredictable effect site equilibration time (fentanyl is more appropriate)
  • fentanyl is often used epidurally and results in significant systemic absorption of drug and resulting side effects
  • sufentanil, alfentanil and remifentanil are phenylpiperidine narcotics used to provide the analgesic component of general anaesthesia. They are very infrequently used in PICU
  • all have predictable effects which include respiratory depression, cough suppression, sedation, meiosis, biliary spasm, constipation, nausea and vomiting, urinary retention and cutaneous flushing (especially about the face)

Benzodiazepines (see table):

  • midazolam and diazepam are effective sedative agents commonly used in PICU
  • they are direct myocardial depressants via blockade of voltage-gated calcium channels (use carefully in patients with LCOS)
  • midazolam is also used to acutely treat seizures in bolus doses and in infusions (up to 1 mg/kg/hour)
  • they are less likely to produce withdrawal syndromes than barbiturates and narcotics (but no analgesic effect)

Alpha2 agonists (see table):

  • clonidine and dexmedetomidine are sedative/anaesthetic agents employed as sedatives in PICU; they also treat symptoms of drug withdrawal
  • their main advantage is lack of respiratory depression which allows quicker weaning of mechanical ventilation
  • they obtund central (brain and spinal cord) sympathetic outflow resulting in negative inotropy and chronotropy and so should not be combined with direct myocardial depressants (benzodiazepines, propofol etc.) in patients at risk of (or in established) LCOS.
  • they cannot be bloused as this can lead to transient alpha1-agonism and severe hypertension

Local anaesthetics:

  • local anaesthetics block voltage gated sodium channels and so prevent conduction along central and peripheral nerve pathways
  • lignocaine is commonly locally infiltrated for short painful procedures (e.g. suturing, insertion of chest drains etc)
  • bupivacaine and ropivacaine are generally used for regional blocks and neuraxial infusions
  • levobupivacaine (S-bupivacaine) and ropivacaine are enantiopure preparations. Cardiotoxicity is less
  • 0.5% solutions contain 5 mg/mL; 1% solutions contain 10 mg/mL; 2% solutions contain 20 mg/mL etc. (1% = 10 mg/ml)
  • onset of effect is related to the pKa of the drug; potency is related to lipid solubility; and duration of action is related to protein binding
  • systemic absorption of local anaesthetics depends on site of infiltration: intercostal > subarachnoid > epidural > brachial plexus > femoral > subcutaneous
  • vasoconstrictors (adrenaline) slow systemic absorption and increase the maximum safe dose
  • EMLA is a mixture of 2.5% lignocaine and 2.5% prilocaine used for topical anaesthesia prior to cannulation/incision; prilocaine can inducemMethaemoglobinaemia and application to mucous membranes will result in rapid systemic absorption of drug
  • CNS toxicity manifests first as excitatory phenomena (circumoral tingling, tinnitus, dizziness and tremors/seizures) followed by CNS depression (unconsciousness, apnoea and coma)
  • CVS toxicity manifests as systemic hypotension, myocardial depression, ventricular arrhythmias and cardiovascular collapse
  • treatment of local anaesthetic toxicity is by supportive therapy (airway management, treatment of seizures with benzodiazepines, fluids +/- inotropes/vascoconstrictors) and administration of 20% lipid emulsion (Intralipid) if in cardiac arrest: 1.5 mL/kg over 1 minute followed by an infusion of 0.25-0.5 ml/kg/min; repeat bolus doses every 5 minutes during CPR

Non-steroidal anti-inflammatory drugs (NSAIDs):

  • classified as specific (COX-2 e.g. parecoxib) or non-specific (COX-1 and COX-2 e.g. ibuprofen)
  • adverse GI effects are due to decreased mucosal blood flow and decreased secretion of mucus and bicarbonate
  • platelet thromboxane A2 is produced from prostaglandins and so NSAIDs impair platelet aggregation
  • prostaglandins are vasodilators involved in physiologic control of vasomotor tone (especially in the kidneys) and their inhibition leads to unopposed vasoconstriction
  • inhibition of prostaglandin synthesis leads to shunting of arachnidonic acid to lypoxygenase which is a bronchoconstrictor
  • specific COX-2 inhibitors are considered to lack effects on platelets and the GIT but will still affect vasomotor tone
  • their use in PICU needs careful consideration due to their wide range of potential side effects
  • paracetamol is generally considered a (central) COX-3 inhibitor; it also acts peripherally by inhibiting bradykinin-chemoreceptor associated pain impulse generation

Other (see table):

  • chloral hydrate is a prodrug that produces the halogenated alcohol chloroethanol; its mechanism is poorly understood but probably acts in a similar way to the volatile halogenated gases via central GABA-A receptors
  • first-generation antihistamines (e.g. promethazine, cyclizine etc.) are also effective sedatives by virtue of their anticholinergic properties; they are generally only used when specific antihistaminergic and/or anticholinergic properties are desired (e.g. antisialogogue for secretions, antitussive)Table: intravenous anesthetic agents
    Thiopentone Propofol Ketamine
    Type/class Barbiturate Isopropylphenol Phencyclidine
    Mechanism GABAA & glycine agonist GABAA & glycine direct agonist and central nicotinic antagonist(Possible 5HT3 blockade) NMDA non-competitive antagonist & blocks central catecholamine reuptake
    Oral bioavailability 25%
    Oral dose n/a n/a 5mg/kg
    IV Bolus 2-7mg/kg 1.5-2.5mg/kg 0.25-0.5mg/kg (analgesia)1-5mg/kg (GA)
    IV Infusion 1-5mg/kg/hour 1-4mg/kg/hour (sedation)5-15mg/kg/hour (GA) 10-40mcg/kg/hour
    Onset time IV < 30seconds < 30seconds 30-60seconds
    ESET 30 seconds < 30 seconds 60seconds
    pKa 7.6 11 7.5
    UNionised fraction 60% > 99% 45%
    Protein binding 80% 99% 25%
    Vd 2.5L/kg 4L/kg 3L/kg
    Clearance 3mL/min/kg 50mL/min/kg 15mL/min/kg
    t ½-dist 8minutes 4 minutes 12minutes
    t ½-elim 12hours 30-60minutes 2-3hours
    Metabolism Hepatic (may become zero-order with prolonged infusion)Some active metabolites Hepatic (CYP2C9 & 2B6) & extrahepatic (site/s unknown)Inactive metabolites HepaticActive metabolites
    Excretion Urine Urine Urine
    Hepatic failure No effect No effect Decreased clearance
    Renal failure Active metabolites will accumulate No effect No effect
    Pros Rapid onsetAnticonvulsantCan produce isoelectric EEG (maximal decreased cerebral metabolic O2 demand)

    Rapid onset & titratabilityBronchodilatorWill obtund airway reflexesAnticonvulsant

    Antiemetic & antipruritic properties at low doses

    Can produce isoelectric EEG

    Mild analgesic properties

    Stable CSHT (<40mins even after >8 hrs infusion)

    Intense analgesia at low doseFavourable haemodynamic profile due to increased central sympathetic outflowBronchodilatorPrevents & treats opioid tolerance

    No respiratory depression/apnoea

    Cons

    Resp depression/apnoeaAntanalgesicCan produce paradoxical excitementWill accumulate with prolonged infusion (long CSHT)

    Tolerance & withdrawal are a problem

    Resp depression/apnoeaMyocardial depressantCan cause a refractory bradycardia (need β-agonist)Rarely causes propofol-infusion syndrome

    Formulation contains soybean oil & egg lecithin

    Myocardial depressantEmergence delirium (especially in older patients – consider midazolam)Increased secretions (consider glycopyrrolate)BrainZ/BIS inaccurate
    Other points ↓BP (↓SVR)↑HR (reflex)Won’t obtund airway reflexesRacaemic formulation ↓BP(↓SVR & ↓CO)↓HR (obtunded baroreceptor reflex) EEG dissociation between thalamus & cortexWon’t obtund airway reflexesTypical induction agent in asthma & sepsis

    Table: benzodiazepines

    Midazolam Diazepam Flumazenil
    Type/class BDZ BDZ BDZ
    Mechanism GABAA receptor indirect-agonist GABAA receptor indirect-agonist BDZ receptor competitive antagonist
    Oral bioavail 40% 95% 25%
    Oral dose 0.5mg/kg up to 20mg 0.05-0.2mg/kg n/a
    IV Bolus 0.05-0.2mg/kgup to 5mg/dose 0.05-0.4mg/kgup to 10mg/dose 8-15mcg/kgup to 200mcg/dose
    IV Infusion 10-100mcg/kg/hour n/a 2-10mcg/kg/hour
    Onset time IV 1-2mins 1-2mins 1-2mins
    ESET 5mins 5mins 5-10mins
    pKa 6.2 3.3 1.8
    % UNionised 90% >99% >99%
    Protein binding 95% 95% 50%
    Vd 1.5L/kg 1.5L/kg 0.5L/kg
    Clearance 10mL/min/kg 1mL/min/kg 20mL/min/kg
    t ½-dist 5mins 5mins 5mins
    t ½-elim 1-4 hours 24-36 hours 60mins
    Metabolism Hepatic (CYP3A4)Active metabolites Hepatic (CYP3A4/5)Active metabolites HepaticNo active metabolites
    Excretion Urine Urine 90% urine
    10% bile
    Hepatic failure Decreased clearance Decreased clearance Decreased clearance
    Renal failure Active metabolite may accumulate Active metabolites will accumulate No effect
    Pros Sedation, amnesia & anxiolysisAnticonvulsantDecreases cerebral metabolic O2 demand Effective orallySedation, amnesia & anxiolysisAnticonvulsantDecreases cerebral metabolic O2 demand Allows specific reversal of BDZ component of resp depression and / or polypharmacy overdoseRarely causes acute anxiety &/or agitation
    Cons Myocardial depressantResp depressionCan cause paradoxical excitement Myocardial depressantResp depressionCan cause paradoxical excitementPainful on injection Can precipitate seizures in epileptics on maintenance BDZs
    Other points ↓BP(↓SVR & ↓CO)[↑HR (reflex)] ↓BP(↓SVR & ↓CO)[HR (reflex)] Is probably a partial agonist

    Table: narcotics

    Morphine Fentanyl Methadone Naloxone
    Type/class Phenanthrene opiate Phenylpiperidine opioid Diphenyl-propylamine opioid Phenanthrene opioid
    Mechanism Non-specific OR agonist MOR agonist with some mild activity at KORs MOR agonist (L-isomer) & NMDA antagonist (D-isomer) Non-specific OR competitive antagonist
    Oral Bioavail. 30% n/a 75% <1%
    Oral dose 0.2-0.5mg/kg q4-6h n/a 0.1-0.2mg/kg q6-24h n/a
    IV bolus dose 0.05-0.2mg/kg 1-10mcg/kg 0.1mg/kg 10mcg/kg
    IV infusion 5-100 mcg/kg/hr 1-10 mcg/kg/hr n/a 10 mcg/kg/hr
    Onset time IV 15-30mins 1-2mins 10-20mins 1-2mins
    ESET 30-90mins 3-6mins 10-20mins 5-10mins
    pKa 8.0 8.4 9.2 7.9
    % UNionised 25% 10% 1% 30%
    Protein binding 35% 85% 90% 50%
    Vd 3L/kg 4L/kg 3.5L/kg 0.2L/kg
    Clearance 25
    mL/min/kg
    10-20 mL/min/kg 1-3 mL/min/kg 30 mL/min/kg
    t ½-dist 2-3mins 1-2mins 1-2 mins
    t ½-elim 2-4hours 2-4hours 18-36 hours 45-60mins
    Metabolism Hepatic & renal10% to active M6G Hepatic (CYP3A4)No active metabolites Hepatic (CYP3A4)No active metabolites HepaticNo active metabolite
    Excretion 90% urine
    10% bile
    90% bile
    10% urine
    50% urine
    50% bile
    Urine
    Hepatic failure May precipitate encephalopathy No effect reduced clearance reduced clearance
    Renal failure Morphine & M6G will accumulate No effect No effect No effect
    Pros No myocardial depressionSedation & euphoriaAntitussive No myocardial depressionSedation & euphoriaAntitussiveNo histamine release Effective enterallyHelpful in withdrawal syndromesSuitable for chronic pain (NMDA actions) Acts rapidly & is titratableAntiinflammatory properties
    Cons

    Respiratory depressionHistamine releaseNausea & vomitingPruritis

    Urinary retention

    Constipation

    Respiratory depressionNausea & vomitingPruritisUrinary retention

    Constipation

    Prolonged CSHT

    Respiratory depressionNausea & vomitingConstipationHistamine release possible but rare

    Prolongs QT interval

    Can precipitate acute withdrawalRarely may cause pulmonary oedema & arrhythmiaUsually needs repeat dosing
    Other points Meiosis↓ HR & BP (↓SVR) Meiosis↓ HR & BP (↓SVR) Meiosis↓ HR & BP (↓SVR) 1mcg/kg effective for narcotic pruritisBP may rise or fall

    Table: alpha2 agonists

    Clonidine Dexmedetomidine
    Type/class Synthetic imidazoline Synthetic imidazoline
    Mechanism α2 adrenoceptor partial agonist α2 adrenoceptor agonist
    Oral bioavail >99% 15%
    Oral dose 1-5mcg/kg up to 300mcg n/a
    IV bolus dose 1-5mcg/kg 1-2mcg/kg
    IV infusion dose 0.5-2mcg/kg/hour 0.2-0.7mcg/kg/hour (sedation)5-10mcg/kg/hour (GA)
    Onset time IV 10-30minutes 10minutes
    ESET 20-30minutes 10-20minutes
    pKa 8.0 7.1
    UNionised % 20% 50%
    Protein binding 20% 95%
    Vd 2L/kg 1.5L/kg
    Clearance 5mL/min/kg 10mL/min/kg
    t ½-dist 30minutes 10 minutes
    t ½-elim 12-18hours 2-3hours
    Metabolism 50% hepatic50% excreted unchanged HepaticNo active metabolites
    Excretion Urine (50% unchanged) Urine
    Hepatic failure No effect Decreased clearance
    Renal failure Active drug will accumulate No effect
    Pros

    Effective sedativeNo respiratory depressionSpinal-mediated analgesia (very effective neuraxially)Known to be useful in opioid & alcohol withdrawal syndromes

    Raises the shivering threshold

    Prolongs regional block by local anaesthetics

    Effective sedativeNo respiratory depressionSpinal-mediated analgesiaUseful for symptoms of opioid withdrawal

    Raises shivering threshold

    Prolongs regional block by local anaesthetics

    Short(er) half time

    Cons

    Rapid IV administration will agonise α1 receptors (↑BP)Negative inotropy & chronotropyDry mouthRebound hypertension can occur (worse if patient is on a TCA or β-blocker)

    Long half time

    Rapid IV administration will agonise α1 receptors (↑BP)Negative inotropy & chronotropyDry mouthCannot be used neuraxially due to glycine in preparation
    Other points ↓HR & ↓BP↓CODry mouth may be used therapeutically if secretions are an issue ↓HR & ↓BP↓CODry mouth may be used therapeutically if secretions are an issue

    Table: others

    Chloral hydrate Promethazine
    Type/class Halogenated alcohol Phenothiazine
    Mechanism Prodrug – below data is for trichloroethanol (active drug)Probably a GABAA agonist H1 receptor antagonist & anticholinergic (antimuscurinic)
    Oral bioavail >99% 25%
    Oral dose 10-100mg/kg 0.25-1.5mg/kg
    IV bolus dose n/a 0.25-1.5mg/kg
    IV infusion dose n/a n/a
    Onset time IV 15minutes (oral) 30-60minutes
    ESET 30-60minutes (oral) 1-3hours
    pKa 12.7 9.1
    UNionised % >99% <1%
    Protein binding 50% 80%
    Vd 1L/kg 7L/kg
    Clearance not known 15mL/min/kg
    t ½-dist n/a 1-2hours
    t ½-elim 4-8hours 12hours
    Metabolism HepaticMetabolites of trichloro-ethanol are inactive Hepatic (CYP2D6)Inactive metabolites
    Excretion Urine Urine
    Hepatic failure Decreased clearance Decreased clearance
    Renal failure No effect No effect
    Pros

    Effective sedative & anxiolyticRapid onset following enteral administrationMild anticonvulsantRelatively wide therapeutic index

    Minimal interference with REM-sleep

    Effective antihistamine & antiemetic at low dosesEffective sedative/hypnotic at high dosesAntitussiveEffective in motion sickness

    Useful in allergic pruritis but not opioid induced pruritis

    Respiratory depression is rare

    Cons

    Respiratory depression in high dosesIrritant to GI mucosaArrhythmias in high dosesTrigger for porphyria

    Patients can develop tolerance & withdrawal

    Anticholinergic effects (dry mouth, blurred vision, urinary retention etc)Central anticholinergic syndrome in overdoseProlonged QT-interval & AV-blockParadoxical excitement may occur
    Other points ↓BP (↓SVR)↑HR (reflex)Actual half time of chloral hydrate is minutes (metabolised by esterases) [↑HR & ↑BP]Antidopaminergic propertiesLocal anaesthetic properties

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