Pain: Postoperative Analgesia in Infants and Neonates

Pain affects almost everyone at some point in his or her life. A definition drawn up by the International Association for the Study of Pain (IASP) has it that pain is always subjective This would seem to imply that the way in which pain is perceived varies from person to person and may also be influenced by the setting and previous experiences. The same definition states that “inability to communicate verbally does not negate the possibility that an individual is experiencing pain and is in need of appropriate pain-relieving treatment”. This truth has a bearing on neonates and children with profound cognitive impairment, who are not able to verbally express their pain, anxiety or other sources of distress. Therefore caregivers in the hospital setting need to find other ways to recognize pain. Early recognition is important because pain requires prompt and adequate treatment, also to prevent possible long-term sequelae. Stress hormone levels have been studied in premature neonates who underwent surgery without perioperative analgesia; levels of cortisol, aldosterone, and other corticosteroids were markedly increased, signifying high stress. In the intensive care unit (ICU) setting, stress and agitation resulting from pain and anxiety can lead children to accidentally remove medical devices endangering the child’s safety. Pain (and therefore stress) is a common condition on the ICU. Previous studies have shown that children in the ICU setting daily undergo many painful procedures, including IV canula insertion or removal, suctioning and heelstick. What’s more, a 2008 survey showed that 80% of these procedures are performed without analgesics

Quantifying the Pharmacodynamics of Morphine in the Treatment of Postoperative Pain in Preverbal Children

While the pharmacokinetics of morphine in children have been studied extensively, little is known about the pharmacodynamics of morphine in this population. Here, we quantified the concentration‐effect relationship of morphine for postoperative pain in preverbal children between 0 and 3 years of age. For this, we applied item response theory modeling in the pharmacokinetic/pharmacodynamic analysis of COMFORT‐Behavior (COMFORT‐B) scale data from 2 previous clinical studies. In the model, we identified a sigmoid maximal efficacy model for the effect of morphine and found that in 26% of children, increasing morphine concentrations were not associated with lower pain scores (nonresponders to morphine up‐titration). In responders to morphine up‐titration, the COMFORT‐B score slowly decreases with increasing morphine concentrations at morphine concentrations >20 ng/mL. In nonresponding children, no decrease in COMFORT‐B score is expected. In general, lower baseline COMFORT‐B scores (2.1 points on average) in younger children (postnatal age 10 days. These findings support a dosing regimen previously suggested by Krekels et al, which would put >95% of patients within this morphine target concentration range at steady state. Our modeling approach provides a promising platform for pharmacodynamic research of analgesics and sedatives in children

Endpoints in pediatric pain studies

Assessing pain intensity in (preverbal) children is more difficult than in adults. Tools to measure pain are being used as primary endpoints [e.g., pain intensity, time to first (rescue) analgesia, total analgesic consumption, adverse effects, and long-term effects] in studies on the effects of analgesic drugs. Here, we review current and promising new endpoints used in pediatric pain assessment studies

Does minimal access major surgery in the newborn hurt less? An evaluation of cumulative opioid doses

Background: Minimal access surgery (MAS) in adults is associated with less postoperative pain in comparison to conventional 'open' surgery. It is not known whether this holds true for neonates as well. Less pain would imply that opioid consumption can be reduced, which has a beneficial effect on morbidity. Aim: To evaluate potential differences in' opioid consumption between neonates undergoing thoracoscopic minimal access surgery or conventional surgery of esophageal atresia (EA) and congenital diaphragmatic hernia (CDH). Methods: In this retrospective cohort study we included two controls for each MAS patient, matched on diagnosis, sex and age at surgery. Opioid dose titration was based on validated pain scores (VAS and COMFORT behaviour), applied by protocol. Cumulative opioid doses at 12, 24, 48 h and 7 days postoperatively were compared between groups with the Mann-Whitney test. Results: The study group consisted of 24 MAS patients (14 EA; 10 CDH). These were matched to 48 control patients (28 EA; 20 CDH). At none of the time points cumulative opioid (median in mg/kg (IQR)) doses significantly differed between MAS patients and controls, both with CDH and EA. For example at 24 h postoperative for CDH patients cumulative opioid doses were [0.84(0.61-1.83) MAS vs. 1.06(0.60-1.36) p = 1.0] controls, For EA patients at 24 h the cumulative opioid doses were [0.48(0.30-0.75) MAS vs. 0.49(0.35-0.79) p = 0.83] controls. This held true for the postoperative pain scores as well. Conclusions: Minimal access surgery for the repair of esophageal atresia or congenital diaphragmatic hernia is not associated with less cumulative opioid doses. (C) 2010 Published by Elsevier Ltd. on behalf of European Federation of International Association for the Study of Pain Chapters

Protocolized post-operative pain management in infants; do we stick to it?

Background: The American Academy of Pediatrics states that ongoing assessment of pain is essential for adequate pain treatment. Pain assessment by means of the COMFORT behaviour scale and the Numeric Rating Scale is therefore an important component of the post-operative pain treatment protocol for neonates and infants in our intensive care unit (ICU). Aim: The study aims to determine degrees of staff compliance with this protocol. Patients and methods: This retrospective chart review concerned post-surgical patients under the age of 3 years admitted to our level III ICU over a 1-year period. The degree of compliance to the post-operative pain protocol was measured by the frequency of deviations from protocol-dictated drug treatment and pain assessments. Results: Records of 200 children with a median age at surgery of 98 days (interquartile range 6-320) were analysed. A mean of 11 assessments in the first 72 h post-operatively per patient had been recorded. A total of 2103 pain assessments were retrieved, of which 1675 (79.7%) suggested comfort. Compliance to the protocol (reassessment and correct medication) was provided in 66 (15.4%) of the 428 assessments suggesting pain or distress. Conclusion: The post-operative pain protocol applied in our ICU appears to be effective; however, full compliance to the protocol was marginal, possibly leading to under-treatment of pain

Evaluation of drug formularies for pediatric intensive care

Objectives: To evaluate availability and reliability of pediatric drug dosing guidelines in selected formularies for intensive care patients. Most drugs used in the pediatric intensive care unit are prescribed off-label, often on the guidance of limited information from commonly used drug formularies. Design: Availability of dosing information on prescribed drugs in a Dutch intensive care unit from January 1, 2005 to December 31, 2006 was compared among four selected formularies (Micromedex, Lexi-Comp, Drug Formulary for Children, Drug Doses). Reliability of dosing guidelines was assessed by evaluating labeling status and literature data for the three most (midazolam, acetaminophen, and amoxicillin/clavulanic acid) and the three least (bosentan, ketanserin, and iloprost) prescribed drugs. Measurements and Main Results: The selected formularies covered 68% to 86% of all 257 prescribed drugs. Guidelines differ widely on daily doses per kilogram, dose description, dosing regimen, and age ranges. For the three most prescribed and one of the least prescribed drugs (bosentan), dosing guidelines adequately reflected labeling status and existing (but scarce) literature. No dosing guidelines were available for iloprost, and only one dosing guideline was available for ketanserin. Conclusions: This study shows that four commonly used drug formularies give few and widely differing dosing guidelines for drugs prescribed in the intensive care unit. If guidelines exist, they seem to reflect labeling status (if present) and limited literature available. Findings from this study likely reflect the scarcity of drug studies in this population. Physicians should be aware of the limitations of these formularies for daily practice in this group of vulnerable patients. (Pediatr Crit Care Med 2011; 12:e14-e19