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Perspective
Doing the right thing Martin Ward Platt Perspective on the paper by Bellù and Milesi et al (see pages 241 and 272). Pain, stress, distress and discomfort. All these words relate to the subjective experience of intensive care for adults and children. Babies, whether term or preterm, undergo experiences that these words might well describe, but unfortunately they cannot tell us about them. This does not make studies of pain in babies undergoing intensive care any less important, it just makes them more difficult. If there has been one important development in humanising neonatal care in the last two decades, it has been the recognition that pain matters; this realisation has resulted in a great deal of research effort to create a scientific underpinning for improved clinical practice. In this issue, Bellù et al have undertaken a meta-analysis of the use of opioids in neonates receiving mechanical ventilation,1 and Milesi et al report on the validation of a new neonatal pain scale that does not rely on facial expression. 2 Where do these two papers take us? There are two main difficulties with clinical studies of pain in babies. The fi rst is trying to fi nd a valid surrogate measure of pain intensity, since asking babies to rate their pain is not possible. The second is to deal with the very different kinds of pain (or distress, or discomfort) that babies have to contend with during their intensive care experience. Let’s take the validity fi rst. This is simple: since no rating of pain intensity can ever be measured against self-report, no scale of pain in the neonate can be validated, or calibrated, against the gold standard of subjective experience. A measure may have construct and face validity (fitting with our adult notions of baby behaviours that common experience show to be related to acute pain), and the measure may show evidence of discrimination in intensity, but this is not the same thing as the validity that Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, UK Correspondence to Dr Martin Ward Platt, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, UK;
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is needed in studies of pain in adults and older children. The problem is that in the absence of the baby’s own descriptive verbal input, all other measures (including behaviour, physiological changes and functional imaging) are, in the end, a circular argument, based on the assumption that the changes measured are a reliable proxy for the baby’s perceptions of what we believe to be painful. This argument is undermined if it emerges that under certain circumstances there is discordance between the observations and the experience, as has recently been suggested for behavioural measures of sucrose analgesia. 3 Then there is the context. Procedural pain has been the most studied, since its onset, offset and duration are reasonably predictable and can be controlled to a large degree, hence the proliferation of studies relating to procedural pain. In accordance with this, Milesi et al’s study focuses on the pain of heel prick. But the experience of procedural pain, though important in its own right, is quite different to postoperative pain, and is also different to the stress and discomfort of mechanical ventilation. In ventilation, the presence of the endotracheal tube and the process of mechanical ventilation are unpleasant; but the process of mechanical ventilation is not painful in the same way that cannulation and suction are painful. In neonates as in older children, the behavioural expressions related to the discomfort of ventilation and to postoperative pain are completely different to those of acute procedural pain, yet a scale developed for measuring procedural pain, such as the Premature Infant Pain Profi le (PIPP), is commonly used in other contexts for which it was not developed, and in which its validity is at best questionable and at worst non-existent. Milesi et al appear to have justification in showing that acute pain can be rated without knowledge of facial expression, and this is clinically a useful development; but no one should assume that their new scale can be used outside the experience of acute procedural pain. Questionable validity is therefore the fi rst problem that has to be confronted when interpreting the results of trials that purport to examine the ‘effectiveness’ of morphine and other opiates in babies
subjected to medical intensive care. The fact that Bellù et al were able to identify some high-quality trials with good blinding and other appropriate characteristics cannot obscure the fact that the measure being used might well not be valid. The second problem lies in an understanding of what one is trying to achieve by using a drug such as morphine, and what other ‘purer’ opioids achieve. It is often forgotten that in addition to being analgesic, morphine is narcotic (it makes you sleepy), euphoric (it makes you feel better) and antitussive (it suppresses the cough reflex). And it is also known to ameliorate the sympathetic nervous system response to procedures such as endotracheal suction. ‘Purer’ opioids such as alfentanil are more powerfully analgesic, but more weakly narcotic, euphoric and antitussive than morphine; yet these other effects are highly desirable in improving the experience of intensive care. Needless to say, although sleepiness and mood are not easy to measure in babies, their improvement is an important component of the alleviation of distress. Therefore any trial confi ned to the assessment of pain, even if perfectly constructed and using a measure with good evidence for validity, would still be in danger of missing the point about improving the subjective experience of intensive care. The fi rst conclusion of the meta-analysis is that “There is insufficient evidence to recommend routine use of opioids in mechanically ventilated newborns”. To which I would add that there is also insufficient evidence to justify withholding morphine in ventilated newborns, given its other desirable effects and the difficulty all researchers have had in identifying significant adverse effects. To those who point out that, rarely, some babies may become hypotensive when given morphine, my reply is to ask, “is it better to bring up the blood pressure by withholding morphine, which will maximise pain and produce endogenous catecholamines, or give morphine and prescribe an inotrope if necessary?” The second conclusion of the metaanalysis is that morphine may be safer than midazolam. Midazolam is sedative and anxiolytic, but is neither antitussive nor analgesic, so for use in isolation it is a poor choice on fi rst principles. In my view it is best reserved for treating seizures. So, faced with the humanitarian need to minimise distress, discomfort and pain, what should we give to Arch Dis Child Fetal Neonatal Ed July 2010 Vol 95 No 4
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Perspective mechanically ventilated babies? In the short term, morphine remains a good choice, based on such clinical and experimental knowledge as we have. Also, any non-pharmacological strategy that shortens the duration of tracheal intubation will improve babies’ experiences. We should not forget that babies habituate to the presence of an endotracheal tube, and commonly appear more comfortable when given charge of their own ventilation without the presence of drugs that suppress their respiratory drive. This implies that ventilator-driven mandatory ventilation may be more subjectively unpleasant than patient-activated ventilation, and that strategies such as tuning a baby’s ventilation to minimise their discomfort may be at least as important to their subjective wellbeing as the choice of pharmacological agent. Other important questions on which we need more work include the relative
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merits of intermittent opiate injection versus, or alongside, continuous infusion; how best to minimise the discomfort and distress of babies who are paralysed, especially term babies with conditions such as diaphragmatic hernia, persistent pulmonary hypertension or septicaemia; and the best regimen for analgesia for babies of any gestation in the fi rst 2 or 3 days after surgery. Even with our rapidly advancing knowledge of infant pain biology,4 there is little immediate prospect of developing routinely applicable means to discern babies’ subjective experiences of pain and distress. We know that neonatal pain experiences have adverse effects on pain perception that persist well into childhood. We therefore cannot assume that the precautionary principle is to ignore the plight of babies who are being mechanically ventilated, especially since the data imply the general safety of
opioid treatments in general, and morphine (with its wide spectrum of desirable effects) in particular. Doing the right thing means ensuring that if in doubt, babies should be made more comfortable, not less. Provenance and peer review Commissioned; externally peer reviewed. Arch Dis Child Fetal Neonatal Ed 2010;95:F232–233. doi:10.1136/adc.2009.169615
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Bellù R, Dewaal K, Zanini R. Opioids for neonates receiving mechanical ventilation. A systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2009. 95;241–51. Milesi C, Cambonie G, Jacquot A, et al. Validation of a neonatal pain scale without facial items. Arch Dis Child Fetal Neonatal Ed 2009:95;272–5. Fitzgerald M. When is an analgesic not an analgesic? Pain 2009;144:9. Fitzgerald M, Walker SM. Infant pain management: a developmental neurobiological approach. Nat Clin Pract Neurol 2009;5:35–50.
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Doing the right thing Martin Ward Platt Arch Dis Child Fetal Neonatal Ed 2010 95: F232-F233
doi: 10.1136/adc.2009.169615
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