July 8, 2008 — Over a 2-week period, neonates in intensive care underwent a median of 10 painful procedures per day, 79% without analgesia, in a  study from Paris.

"The number of painful procedures is so high that the first step to improve procedural pain management must significantly reduce these numbers," the authors, led by Ricardo Carbajal,
MD, from the Hôpital d'enfants Armand Trousseau, in Paris, France, write.

"The knowledge that some vulnerable neonates underwent 153 tracheal aspirations or 95 heel sticks in a 2-week period should elicit a thoughtful and relevant analysis on the necessity and the risk/benefit ratio for our clinical practices," they observe.

The study is published in the July 2 issue of the Journal of the American Medical Association.

Vulnerable Neonates, Long-Term Consequences From Pain

Compared with older children and adults, neonates are more sensitive to pain, and multiple lines of evidence suggests that repeated and prolonged exposure to pain alters a neonate's subsequent pain processing, long-term development, and behavior. "It is essential, therefore, to prevent or treat pain in neonates," and there are numerous pharmacological and nonpharmacological treatments that can alleviate procedural pain in these infants, the group writes.

Effective strategies to improve pain management in neonates require a clear understanding of the epidemiology and management of procedural pain, they add.

They aimed to report the findings from epidemiological data on neonatal pain collected from direct bedside observations of neonates in Paris as part of the Epidemiology of Procedural Pain in Neonates (EPIPPAIN) study.

This prospective observational study collected around-the-clock bedside data on all painful or stressful procedures performed in 430 neonates admitted to 13 of 14 intensive care units in tertiary care centers in Paris. Data were collected from the first 14 days of admission, during a 6-week period.

Painful procedures were considered as those that invaded a neonate's bodily integrity, and stressful procedures were defined as those that mainly caused physical uneasiness or annoyance.

Nonpharmacological analgesia included administering sweet solutions or allowing nonnutritive sucking. Pharmacological analgesia included intravenous opioids and topical drugs.

The average gestational age was 33 weeks and the average intensive care unit stay was 8.4 days.

The investigators identified 44 painful procedures, of which the 6 most common were nasal aspiration (28.9% of the procedures), tracheal aspiration (23.3%), heel stick (19.8%), adhesive removal (12.7%), gastric tube insertion (2.4%), and venipuncture (1.8%).

Of the 16 identified stressful procedures, the 6 most frequent were nursing care (39.2%), oral aspiration (26.9%), washing the neonate (8.5%), blood pressure measurement (8.5%), X-rays (6.0%), and infant weighing (5.8%).

Average of 16 Painful or Stressful Procedures Each Day

During the study period, neonates experienced 42,413 painful and 18,556 stressful first-attempt procedures and 10,366 painful and 1180 stressful supplemental-attempt procedures.

Each neonate experienced a mean of 16 painful plus stressful procedures each day, and some experienced as many as 62 procedures each day.

Number of Painful and Stressful Procedures in Neonates in ICU

Procedure      In 2 Weeks      Per Day
                141 (107)      16 (9)

Painful or stressful procedures, n, mean (SD)      
                 98 (78)      12 (8)

Painful procedures, n, mean (SD)      
                115 (4 – 613)      16 ( 0 – 62)

Painful or stressful procedures, n, median (range)               75 (3 – 364)      10 (0 – 51)

Painful procedures, n, median (range)      

ICU = intensive care unit

Of the 42,413 painful procedures, only 20.8% were carried out with specific analgesia before the procedure: 2.1% were performed with pharmacological-only therapy, 18.2% with nonpharmacological therapy, and 0.4% with both.

"Advances in neonatal care in recent decades, with increased survival of immature and sick neonates, have led to an increased number of invasive procedures that may cause pain in these vulnerable neonates," the group writes. "The prevention of pain in critically ill neonates is not only an ethical obligation, it also averts immediate and long-term consequences," they add.

Clinical Pain Assessment Correlates With Brain Activity

In another study, changes in brain activity in response to a painful stimulus (a heel prick) were well-correlated to facial-expression changes in 33 test occasions in 12 infants. In 10 of the 33 test cases, however, the infants showed a cortical response without a change in facial expression, suggesting that pain assessment based on behavioral tools alone may underestimate pain.

These findings, by Rebeccah Slater, PhD, from University College London, in the United Kingdom, and colleagues, are published online June 24 in PLoS Medicine.

Pain in infancy is poorly understood, the group writes. Current assessment tools such as the premature infant pain profile (PIPP) are based on behavioral measures (changes in facial expression) and physiological measures (changes in heart rate and oxygen saturation).

The ability to use near-infrared spectroscopy to measure changes in oxygenated and deoxygenated hemoglobin concentration in the cortex in response to a noxious stimulus has provided investigators with the first opportunity to evaluate whether pain-assessment tools reflect pain processing in the brain, they add.

The team hypothesized that in infants who received a heel prick, clinical pain scores calculated using the PIPP would correlate with cortical hemodynamic activity.

They studied 12 clinically stable infants in a neonatal unit in a London hospital. The postmenstrual age (gestational age plus postnatal age) of the infants was 25 to 43 weeks, and their postnatal age was 5 to 134 days.

Clinical pain scores — facial expression (eye squeeze, brow bulge, and nasolabial furrow), heart rate, and oxygen saturation — and cortical hemodynamic activity were assessed during 33 clinically required heel pricks.

Behavioral Tools May Underestimate Pain Response

Clinical pain scores, especially facial expression, correlated well with cortical hemodynamic activity, but in some cases, infants did not show changes in facial expression but did show cortical responses to pain.

"While painful stimulation generally evokes parallel cortical and behavioral responses in infants . . . pain assessment based on behavioral tools alone should be interpreted with caution, as they could underestimate the total pain response," the researchers write.

In an accompanying Editors' Summary, A. David Edwards, MD, also from Imperial College London, writes that attention-deficit disorders, learning disorders, and behavioral problems in later childhood may be linked to repetitive pain in the preterm infant.

Concurring with the study authors' conclusions, he notes: "The results of this study raise further awareness of the ability of infants to experience pain and highlight the possibility that pain based on behavioral tools alone may underestimate the pain response in infants."

The JAMA article was supported by funds from the Fondation CNP and the Fondation de France, in France. Lead author Dr. Carbajal is affiliated with the Centre National de Ressources de lutte contre la Douleur. The financial affiliations of the other authors are listed in the article. The PLoS Medicine article was funded by the Wellcome Trust, the Medical Research Council, and SPARKS. The authors have declared that no competing interest exists.

JAMA. 2008;300:60-70. Abstract

PLoS Med. 2008;5:e129. Abstract
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For decades physicians believed that babies and small children did not experience pain as did adults. Clearly they had to turn a deaf ear to their screams and crying to hold on this mythology. The tenacity of a myth can be astonishing. I had assumed a decade ago that the myth had been abandoned. To my utter dismay I find that I was wrong (I have not been in a neonatal intensive care unit for 20 years.)

It is my deepest hope that this article will terminate this barbarism. If it does not, the law should immediately step in. This is a prima facie instance of assault and battery and the perpetrators should be immediately jailed.
J.S. Hochman MD
Executive Director
NFTP