News Author: Marlene Busko

July 11, 2008 — Over a 2-week period, neonates in intensive care underwent a median of 10 painful procedures per day, 79.2% 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 suggest 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,” the group writes, and there are numerous pharmacological and nonpharmacological treatments that can alleviate procedural pain in these infants.

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 epidemiologic data on neonatal pain collected from direct bedside observations of neonates in Paris as part of the Epidemiology of Procedural Pain in Neonates 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.

Nonpharmacologic analgesia included administering sweet solutions or allowing nonnutritive sucking. Pharmacologic 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%), radiographs (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.

Table. Number of Painful and Stressful Procedures in Neonates in ICU*

Procedure In 2 Weeks Per Day
Painful or stressful procedures, n, mean (SD) 141 (107) 16 (9)
Painful procedures, n, mean (SD) 98 (78) 12 (8)
Painful or stressful procedures, n, median (range) 115 (4 – 613) 16 ( 0 – 62)
Painful procedures, n, median (range) 75 (3 – 364) 10 (0 – 51)

*ICU indicates 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 pharmacologic-only therapy, 18.2% with nonpharmacologic 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 physiologic 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 Journal of the American Medical Association 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. A complete list of disclosures is available in the original article. The PLoS Medicine article was funded by the Wellcome Trust, the Medical Research Council, and SPARKS. The study authors have disclosed no relevant financial relationships.

JAMA. 2008;300:60-70.

PLoS Med. 2008;5:e129.

Clinical Context

In the November 2006 issue of Pediatrics, Batton and colleagues reported the recommendation from the American Academy of Pediatrics to minimize painful interventions in neonates. In the 1998 issue of Biology of the Neonate, Amand noted that neonates have greater pain sensitivity than other individuals. In the December 1997 issue of the Clinical Journal of Pain, a multicenter chart review by Johnston and colleagues found that each neonate underwent an average of 2 procedures per day during a 1-week period.

This prospective study uses direct bedside observation to report data on painful or stressful procedures and analgesic therapy in neonates admitted to the intensive care unit.

Study Highlights

  • 430 neonates, including preterm neonates younger than 45 postconceptional weeks and term neonates younger than 28 days, admitted to 8 neonatal intensive care units and 5 pediatric intensive care units in 1 region in France were enrolled.
  • There were no exclusion criteria.
  • Subjects included 309 neonates (71.9%) in neonatal intensive care units and 121 (28.1%) in pediatric intensive care units.
  • Mean gestational age at birth was 33 weeks (range, 24 – 42 weeks).
  • Mean birth weight was 1962 g (range, 490 – 4760 g).
  • 237 (55.1%) were boys.
  • 303 (70.5%) required mechanical tracheal ventilation.
  • Data collection on pain, stress, discomfort, and analgesic therapy occurred for the first 14 days of admission.
  • Mean duration of stay was 8.4 days.
  • 24 (5.6%) died during the study period.
  • No modifications were made in each institution’s pain management protocol.
  • Pharmacologic therapy included intravenous opioids, topical eutectic mixture of lidocaine and prilocaine, or other drugs.
  • Nonpharmacologic therapy included sweet solution, nonnutritive sucking, and skin-to-skin maternal contact.
  • Nursing and medical staff recorded bedside procedures, defined as medical, nursing, surgical, diagnostic, or therapeutic activity performed in the unit.
  • Procedures did not include continuous therapy.
  • Painful procedures were defined either by invasion of the bodily integrity, causing skin or mucosal injury from introducing or removing foreign material into the airway, digestive, or urinary tract, or by clinician assessment.
  • A group of 15 nurses and physicians in the neonatal intensive care unit assigned final classification of painful procedures, defined by a mean score of more than 40 on a 100-point scale.
  • Stressful procedures were defined by physical uneasiness or annoyance or by disturbance of equilibrium between the neonate and the environment.
  • A research assistant verified documentation of procedures up to 3 times per week in each site.
  • 60,969 first-attempt procedures included 42,413 (69.6%) painful and 18,556 (30.4%) stressful procedures.
  • 11,546 supplemental attempts at procedures included 10,366 (89.8%) attempts at painful procedures and 1,180 (10.2%) attempts at stressful procedures.
  • Each neonate underwent an average of 141 procedures (range, 4 – 613 procedures) and 16 procedures per day (range, 0 – 62 procedures).
  • Each neonate underwent an average of 98 painful procedures (range, 3 – 364 procedures) and 10 painful procedures per day (range, 0 – 51 procedures).
  • The most common painful procedures were nasal aspiration (28.9%) and tracheal aspiration (23.3%).
  • The most common stressful procedures were nursing care (39.2%) and oral aspiration (26.9%).
  • Analgesic therapy specifically for painful procedures included pharmacologic-only in 907 (2.1%), nonpharmacologic-only in 7734 (18.2%), both pharmacologic and nonpharmacologic in 164 (0.4%), and none in 33,608 (79.2%).
  • Nonspecific analgesia was received during 14,495 (34.2%) painful procedures.
  • Analgesic therapy specifically for stressful procedures included pharmacologic-only in 136 (0.7%), nonpharmacologic-only in 1077 (5.8%), both pharmacologic and nonpharmacologic in 6 (< 0.1%), and no treatment in 17,337 (93.4%).
  • Nonspecific analgesia was received during 3144 (16.9%) stressful procedures.
  • Factors associated with greater use of specific analgesia included prematurity, parental presence, surgery, daytime (7 AM to 6 PM), category of procedure, and hospitalization days 2 to 14.
  • Factors associated with less use of specific analgesia included mechanical ventilation, noninvasive ventilation, nonspecific analgesia, and higher Clinical Risk Index for Babies score.

Pearls for Practice

  • In the first 14 days of admission to the intensive care unit, each neonate undergoes an average of 16 painful or stressful procedures per day and an average of 12 painful procedures per day.
  • Neonates who undergo painful procedures in the intensive care unit receive specific pharmacologic or nonpharmacologic analgesia in 20% of cases.


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