Improving pain management for children

Morton, Neil S. (2008) Improving pain management for children. MD thesis, University of Glasgow.

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Over the last 20 years it has been realised that neonates, infants and children experience pain and considerable stress responses to surgical and medical procedures which are harmful and cause fear, anxiety and distress(Walker, 2008).
This thesis will describe a body of work published since 1992 whose aim has been to improve several aspects of pain management for children in terms of both efficacy and safety. The studies encompass research into the four main classes of analgesics used in paediatric clinical practice, namely local anaesthetics, opioids, non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol. In addition, control of the stress responses to tracheal intubation and to surgery has been studied with the availability of newer potent short-acting opioid agents and the anaesthetic agent propofol. The total body of work described covers 41 peer reviewed publications with 14 index papers selected for more detailed consideration.
Local anaesthetics
Several studies included in this thesis demonstrate the efficacy and safety of local anaesthetics in children.
The optimum dose of the amide local anaesthetic, lignocaine, was determined for preventing pain on intravenous injection of propofol in children(Cameron et al., 1992) and this resulted in the widespread adoption of propofol as an induction agent. Several studies of propofol in children were conducted and this led to the development of more accurate computer-controlled delivery for maintenance of anaesthesia in children down to age 1 year(Morton et al., 1988, Marsh et al., 1990, Morton, 1990a, Marsh et al., 1991, Doyle et al., 1993c, Runcie et al., 1993, Morton, 1998b, Varveris and Morton, 2002).
Topical amethocaine (as a gel and as a phase-change patch) was evaluated in children(Doyle et al., 1993a, Lawson et al., 1995, Lawson and Morton, 1998) and found to have a significantly more rapid onset of action than EMLA cream. This gel is now widely used in the UK.
For nerve block, the efficacy and safety of fascia iliaca compartment block in children was demonstrated(Doyle et al., 1997) and the additional safety margin provided by adding the vasoconstrictor adrenaline to the local anaesthetic solution was proved by very low peak plasma concentrations of local anaesthetic. This was also demonstrated for caudal epidural blockade in infants(Hansen et al., 2001).
New amide local anaesthetics were introduced in the last decade and ropivacaine was shown to be safe and effective for caudal epidural blockade in children(Ivani et al., 1998a). A collaboration with Strathclyde University led to the development of a new micro-assay method for measurement of local anaesthetics in small volumes of plasma with applicability to neonatal age groups of patients where ethically allowable blood sampling volumes are very small(Stumpe et al., 2000).

The technique of patient-controlled analgesia was studied in children with an open feasibility trial in 1990(Lawrie et al., 1990) using conventional electronic syringe pumps and a further innovative study of a disposable elastomeric reservoir device in 1992(Irwin et al., 1992). The optimum regimen for PCA in children was determined by a series of studies(Doyle et al., 1994a, Doyle et al., 1993d, Doyle et al., 1994c, Munro et al., 2002) and a subsequent trial demonstrated that PCA could be delivered by the subcutaneous route(Doyle et al., 1994b). A further collaboration with Strathclyde produced a microassay method for morphine and metabolites(Watson et al., 1995). These studies showed that PCA is very efficacious and safe for perioperative pain conrol in children from age 5 years upwards and this technique is now in routine use worldwide(Walker, 2008, APAGBI, 2008, Morton, 2007, Lonnqvist and Morton, 2005b).
NSAIDs and Paracetamol
Following the demonstration of the utility of PCA in children, the technique was used to assess the analgesic efficacy of the NSAID diclofenac and paracetamol in children(Morton and O'Brien, 1999). This showed diclofenac to be particularly efficacious in producing a 40% morphine-sparing effect in children. An innovative study of NSAID eye drops showed them to be as effective as local anaesthetic eye drops for providing analgesia after strabismus surgery in children(Morton et al., 1997).
Dosing regimens for paracetamol have evolved in the last decade based on better information on developmental pharmacokinetics and elucidation of the mechanism of action(Arana et al., 2001, Ottani et al., 2006, Pickering et al., 2006, Anderson and Palmer, 2006). There is renewed interest in this decade with the availability of new IV formulations of this old drug. In 1999(Hansen et al., 1999) we contributed to the PK data for paracetamol in neonates and infants which was subsequently used by authors from New Zealand to determine the population PK parameters in this young age group(Anderson and Palmer, 2006). We collated the knowledge on dosing regimens in 2001 in a review(Arana et al., 2001) which has informed the current recommendations in the BNFC. A further collaboration with Strathclyde University led to the development of a microassay for paracetamol and its metabolites from blood spots which has been taken up by Medecins Sans Frontieres as a possible method to use in the field in developing countries(Oliveira et al., 2002). The morphine-sparing efficacy of paracetamol was shown to be less than that due to diclofenac in the study mentioned above under NSAIDs(Morton and O'Brien, 1999).
Controlling the stress response
Noxious stimuli produce a stress response. A series of studies has shown that using short acting opioids, tracheal intubation could be safely performed without the aid of muscle relaxant drugs in children(Steyn et al., 1994, O'Brien et al., 1998, Robinson et al., 1998). This technique is now widely practiced. Two studies explored methods to reduce the stress response to open heart surgery with cardiopulmonary bypass, one of the most potent surgical stressors. Propofol anaesthesia was shown to significantly ameliorate this response(Laycock et al., 1992) and the newer opioid remifentanil was shown to be as efficacious as the older drug fentanyl for this purpose(Bell et al., 2004).

Audit, guidelines and protocols
Two major analgesic techniques have been audited in large national projects looking at the risk of epidural infusions in children(Llewellyn and Moriarty, 2007) and opioid infusion techniques in children (Morton, 2008c) and the results show these techniques to be of comparable safety. The evidence from the past 20 years has recently been synthesised into a clinical guideline for management of postoperative and procedural pain in children which has highlighted good practice based on high quality evidence but also revealed a paucity of evidence in some fields(APAGBI, 2008). Guidelines for safer paediatric procedural sedation practice is also described(SIGN, 2004, Playfor et al., 2006). The implementation of guidelines relies on the development of a local protocol and the evolution of the acute pain relief service protocol in Glasgow is described.(Morton, 2008a)

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: analgesia, paediatric, pain management, children
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RJ Pediatrics > RJ101 Child Health. Child health services
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Kinsella, Professor John
Date of Award: 2008
Depositing User: Dr Neil S. Morton
Unique ID: glathesis:2008-650
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 01 Apr 2009
Last Modified: 18 May 2022 10:51

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