Does the Newborn Infant Parasympathetic Evaluation (NIPE) Index Predict Postsurgical Pain in Children

Pain represents a sensorial experience in response to tissue damage, that does not only affects the emotional and functional domains of an individual, but also leads to multiple detrimental, unanticipated and long-lasting consequences. In fact, pain has been associated with cognitive disturbances, increase in cancer recurrence, impairment in brain development and impairment of the immune system. Pain associated with surgical stress delays postoperative ambulation and discharge, promotes the development of chronic postoperative pain, and increases morbidity and mortality.

Despite the advancement in analgesics and pain control modalities, severe postoperative pain is present in up to 40% of patients. Improved pain management based on an accurate assessment of patients' pain intensity has been associated with better patient outcomes. As a consequence, standardized, validated instruments to facilitate pain evaluation have been recommended by the American Society of Anesthesiologists (ASA) Task Force on Acute Pain Management. Self-report scales, behavioral scales and physiological measures have been developed to assess pain after surgery. These tools, however, are applicable only in awake, cooperative patients and have limited value in uncooperative and non-verbal patients, such as young children.

In recent years, investigations have focused on parasympathetic tone activity as an indirect assessment of the level of pain. While heart rate variability (HRV) is affected by the balance between sympathetic and parasympathetic tone, the high frequency changes of HRV is primarily mediated by and specific to the parasympathetic nervous system. The phenomena of pain, fear, anxiety and intraoperative nociception have proven to be accompanied by changes in HRV. In pediatric patients, HRV analysis correlates with prolonged pain and newborn comfort.

The newborn infant parasympathetic evaluation (NIPE) is a non-invasive, standardized continuous measurement of HRV. The cardiac signal is extrapolated from the electrocardiogram and respiratory rate (RR) series are computed between two heart beats, resampled at 8 Hz, mean centered and normalized over a 64-second moving window. A wavelet based high pass filter over 0.15 Hz is applied in order to keep parasympathetic related variations only, which are mainly influenced by the respiratory cycle. The NIPE monitor displays two averaged measurements: the average NIPE (NIPEa) results from the average of NIPE measured over the previous 20 minutes, and current NIPE (NIPEc) results from the average of NIPE measured over the previous 64 seconds. A non-disclosed algorithm derived from the high frequency changes of the HRV calculates a score between 0 and 100, where a score of 0 indicates minimal parasympathetic tone and maximal nociception and a score of 100 indicates maximal parasympathetic tone and minimal nociception.

The NIPE index is a modification of Analgesia Nociception Index (ANI) and was developed for infants and young children who have higher baseline HR resulting in a lower possible variability. The ANI has shown a good performance in predicting intraoperative nociceptive stimuli in animals, adults7, and older children. In adults, ANI was able to predict the incidence of moderate/severe pain postoperatively and in critically ill patients.

To date, NIPE has shown promising results in the assessment of intraoperative and procedural pain, and neonatal comfort. On the contrary, there is a paucity of literature examining the usefulness of NIPE in guiding postoperative pain management in young children.

The current standard of care relies on scales incorporating various behavioural parameters to evaluate the likelihood of pain and the need for analgesic medication. The most commonly used scales in preschool children, who are not able to complete self-assessments, are the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), the Face, Legs, Activity, Cry and Consolability Scale (FLACC), and the Children and Infants' Postoperative Pain Scale (CHIPPS). These scales are limited in their dependence on examiner's ability to use the tool and training. Recently, the Pediatric Critical-Care Pain Observation Tool (P-CPOT) has been validated in critically ill children, but no data on postsurgical pediatric patients has been published.

The postoperative pain assessment in small children may be confused with Emergence Delirium (ED), an anesthesia related complication that affects 25% children undergoing surgery. ED is associated with significant adverse effects including injury to the patient and personnel, damage to incision sites, exacerbated parental anxiety, and increased nursing requirements, further resulting in an increased burden and cost to the healthcare system. Once ED occurs, extra nursing care may be necessary, as well as supplemental sedative and/or analgesic medications, which may delay patient discharge. Children showing ED after anaesthesia are seven times more likely to have new-onset separation anxiety, apathy, eating and sleeping problems. To date, only the Pediatric Anesthesia Emergence Delirium (PAED) scale has been validated in the pediatric population, but its capability to discriminate between ED and pain has been recently questioned.

In the absence of appropriate diagnostic tools, the management of pain or emergence delirium may be delayed while attempting to treat the other possible confounding conditions that may similarly occur in the Post Anesthesia Care Unit (PACU).