**Abstract**

Limited data are available in the literature on multimodal pain management in extremely low birth weight (ELBW) neonates. This chapter aimed to summarize current knowledge about the effects of analgesics and sedatives (paracetamol, opioids, benzodiazepines and anaesthetics) on postoperative pain management (≤ 48 hours after surgery). The primary endpoints of postoperative pain management were searched using validated pain assessment instruments, such as pain intensity, excessive sedation, drug consumption or adequate rescue medication. The secondary endpoints are the safety parameters of the drugs used, while the determinants of short/long-term outcome (duration of mechanical ventilation, intraventricular haemorrhage—IVH, periventricular leukomalacia—PVL, postnatal growth restriction, stage of chronic lung disease—CLD or neurodevelopmental outcome according to the Bayley-II Scale of Infant Development at 18–24 months or developmental equivalents at early-school age) were assessed as tertiary endpoints. Additionally, one of the most important key elements of clinical science is known as clinical research study validation, including specific tools and techniques within the validation processes. This chapter focuses on postoperative multimodal pain management, including the implementation of pain assessment tools and analgesic and sedative dosing regimens needed to achieve the efficacy and safety goals of an optimal pain profile in ELBW neonates; only proven non-pharmacological procedures are not included.

**Keywords:** extremely low birth weight neonates, postoperative pain, COMFORTneo score, paracetamol, opioid consumption

### **1. Introduction**

Optimal pain management is an essential requirement of the daily clinical practice of a sick neonate and one of the indicators of quality-of-life care. Records of the experience of pain and its short-term and long-term consequences for the immature organism have been increasing in the recent decades, as well as warnings of the

adverse effects of analgesics [1, 2]. A multimodal approach based on the multimodal concept of pain assessment can help to objectivate the diagnosis of pain in patients who are immature or who do not display pain due to severe illness. However, in nonverbal immature individuals, assessing pain or differentiating pain from discomfort is difficult and requires a specific approach and research into new diagnostic methods. The standard in clinical practice is evaluated scales mostly based on behavioural and physiological responses to pain. There are more than 65 assessment scales for childhood, but only a third of them are also validated for immature neonates, and significantly less for extremely low birth weight neonates (ELBW) after major abdominal surgery in particular [3]. Moreover, the choice of pain assessment tools varies among neonatal intensive care units (NICU) and countries as described, for example, in premature neonates treated for necrotizing enterocolitis (NEC) [4]. However, not all of the listed pain scales are validated, particularly for postoperative pain in ELBW.

To achieve the best possible quality in using these scoring systems at individual workplaces, implementing "evidence-based" procedures is necessary, including education with regular evaluation of the reliability and consistency of the staff in the assessment of pain since these methods are largely subjective. Objective methods such as measurement of tissue oxygenation (NIRS-near-infrared spectroscopy), skin conductance (SCM-skin conductance measurement), electroencephalography (EEG), or measurement of cortisol concentration in saliva or adrenaline, noradrenaline and cortisol determination in the blood, and physiological functions are currently auxiliary or research methods [5].

