Pain in Newborns -- Compassion & Common Sense Yeah, Baby!

Neonatal pain Suzanne S. Toce, MD Professor of Pediatrics Saint Louis University Medical Director, FOOTPRINTS Gary Allegretta, M.D. Medical Director The Jason Program Web: www.jasonprogram.org Add Your Logo Here ! Call for Details !

Outline Fundamental principles of neonatal pain Measuring neonatal pain Developmental aspects of pain Pharmacologic treatment of pain Non-pharmacologic treatment of pain

State of the Art Prevention and Management of Pain and Stress in the Neonate (RE9945) --AMERICAN ACADEMY OF PEDIATRICS Committee on Fetus and Newborn Committee on Drugs Section on Anesthesiology Section on Surgery -- Pediatrics Volume 105, Number 2 February 2000, pp 454-461

Studies indicate a lack of awareness among health care professionals of pain perception, assessment, and management in neonates.9-11 When analgesics were used in infants, they often were administered based only on the perceptions of health care professionals or family members. Fear of adverse reactions and toxic effects often contributed to the inadequate use of analgesics. In addition, health care professionals often focused on treatment of pain rather than a systematic approach to reduce or prevent pain.12,13 More recent surveys have demonstrated increased awareness among health care professionals of pain in neonates and infants and its assessment and management.14-16 Several textbooks on pain in neonates and infants have been published,17-19 and measures for assessing pain have been developed and validated.20-24 However, despite the advances in pain assessment and management, prevention and treatment of unnecessary pain attributable to anticipated noxious stimuli remain limited.25-27 Several important concepts must be recognized to provide adequate pain management for the preterm and term neonate:

Fundamental Concepts Babies feel pain despite established myths. Severity of pain and effects of analgesia can be assessed in the neonate.20-24,42-46 Neuroanatomical components and neuroendocrine systems are sufficiently developed to allow transmission of painful stimuli in the neonate.28-32 · Exposure to prolonged or severe pain may increase neonatal morbidity.33-36 · Infants who have experienced pain during the neonatal period respond differently to subsequent painful events.37-41 · Neonates are not easily comforted when analgesia is needed.8 So, lets fix that.

Newborns can’t remember pain Newborns can’t react to pain Newborns don’t feel pain Dispelling the myths

Neonatal Pain Scales Validated and Reliable Scales Exist The Perception Problem - Do we measure pain? Measure Physiologic Parameters Heart rate, resp rate, BP, O2 sats, sweating, vagal tone, plasma cortisol & catechols Measure Behavioral Parameters Facial expressions, body movements, crying Examples

The Perception Problem Green Red Yellow Green Red Yellow

Premature Infant Pain Profile Facial Actions Brow bulge Eye squeeze Nasolabial furrow Physiological Indicators Heart rate Oxygen saturation Context Gestational age Behavioral state Inter-rater reliability >.93

PIPP Scale

CRIES scoring Crying Requirement for oxygen (to keep SaO2 >95%) Increased heart rate and BP Expression Sleeplessness Inter-rater reliability >.72

CRIES Scale

Common Sense = Babies Feel Pain I.M.H.O. Common Sense = Babies Feel Pain

Developmental Aspects of Pain Perception Pain Pathways Reminder Anatomic Development Physiologic Development

Pain Pathways Descending pathways Ascending pathways Peripheral receptors Neural pathways Spinal cord tracts Brainstem, thalamus, & beyond

Anatomic developments Dendritic arborization 21 weeks PCA Nerve tracts in spinal cord 22 weeks PCA and brainstem Connections with 22 weeks PCA thalamocortical fibers

Physiologic Development Lower pain threshold in neonatal rats Neurotransmitter receptors are up-regulated in the neonatal period Neonatal pain processing: Early development of the excitatory mechanisms & later development of inhibition Normal development of the pain system occurs in the absence of noxious stimuli :

Effect of GA on HR Response (tested at <1 week of life) Stimulus Change in HR (+ SE) BPM Mild Moderate High Porter, et al. Pediatrics, 1999

(tested at >36 weeks of life) Effect of GA on HR Response (tested at >36 weeks of life) Stimulus Change in HR (+ SE) BPM Mild Moderate High Porter, et al. Pediatrics, 1999

Prolonged Effects of Pain Alvares, D., et.al. Modeling the Prolonged Effects of Neonatal Pain Progress in Brain Research, Vol. 129, Ch. 27, 2000 Previous Work: Preterm infants show prolonged hyperalgesia within an area of local tissue damage and secondary hyperalgesia in the contralateral limb. Circumcision results in increased pain behavior 3 months later. Birth trauma linked to increased acute stress responses to pain in infancy.

This Study Normal Mouse Nerve

The Problem Repair Response to Wound

Reasons Cited for Not Providing Analgesia During Circumcision First, an Attitude Reasons Cited for Not Providing Analgesia During Circumcision Concern over risks (54%) Not warranted (44%) Lack of familiarity with techniques (18%) Increased time (9%) Pain is inflicted during anesthesia Anesthesia is inadequate/ineffective Pediatrics 1998

Official AAP Policy

Nonpharmacologic treatment of neonatal pain “How sweet for those faring badly to forget their misfortunes for even a short time.” --- Sophocles

Avoid Painful Procedures Painful or stressful procedures should be minimized and, when appropriate, coordinated with other aspects of the neonate’s care. Furthermore, consideration of the least painful method is important. For example, when performed by trained personnel, obtaining blood by venipuncture may be less painful than heel lancing.56-58 Skillful placement of peripheral, central, or arterial lines reduces the need for repeated intravenous punctures or intramuscular injections. Thus, in some such cases, the risk-benefit balance may favor the more invasive indwelling catheters. Whenever possible, validated noninvasive monitoring techniques (e.g., pulse oximetry) that are not tissue damaging should replace invasive methods.

Endogenous analgesic pathways Generalized tactile Orotactile Orogustatory

Tactile: Swaddling Swaddled weighing Less physiologic distress p<0.002 More effective self-regulatory ability p<0.037 Downside: males can’t do this

Tactile: skin-skin contact Percent of time Control Grimace Cry Gray, et al Pediatrics 2000

Orotactile pathways

Non-nutritive sucking Tested during heelstick procedure Heelstick caused no effect on respiratory rate and oxygen saturations Sucking reduced time of crying and heart rate increases --Corbo, et al. Biol Neonate, 2000

Orogustatory

Effect of Oral Sucrose Solution on Venipuncture Pain Abad, et al Acta Paediatr, 1996 Time crying (sec)

Effect of sucrose and procedure on circumcision pain AJOG 2002;186:564-8

Effect of solution and route on heelstick pain NG sucrose Oral sucrose NG water Oral water Percent time crying (Median) Ramenghi, et al ADC (Fetal Neonatal Ed), 1999

Pacifier and Sucrose in Procedural Pain Median pain scale score Carbajal, et al. BMJ, 1999

Glucose for Analgesia Details Crossover Trial of Analgesic Efficacy of Glucose and Pacifier in Very Preterm Neonates During Subcutaneous Injections --- Ricardo Carbajal, MD, et.al.; PEDIATRICS Vol. 110 No. 2 August 2002 40 very preterm neonates receiving erythropoietin injections SQ Primary outcome measure: Douleur Aigue¨ Nouveau-ne´ scale (0-10) Conclusions. A small dose of 0.3 ml of 30% oral glucose has an analgesic effect in very preterm neonates during subcutaneous injections. This effect is clinically evident because it can be detected by a behavioral pain rating scale. The synergetic analgesic effect of glucose plus sucking a pacifier is less obvious in very preterm infants. Details

Fig 1. Individual pain evaluations with DAN scale Fig 1. Individual pain evaluations with DAN scale. Overall, glucose gives lower scores than sterile water (p 0.03); however, 8 infants did not show a reduction of pain scores. Solid black lines indicate infants who did have a reduction in pain. Red lines indicate infants who did not have a reduction in pain scores with 30% glucose as compared to sterile water.

Sugar for analgesia Dose Drug Dispensing 0.12-.48 grams sucrose Sucrose most effective 2ml of 24% solution Dispensing oral only

Breastfeeding is Analgesic in Healthy Newborns -- Gray, et Breastfeeding is Analgesic in Healthy Newborns -- Gray, et.al, Pediatrics Vol. 109, No. 4, April 2002 The purpose of this study was to unite the different components of nursing (taste, suckling, and skin-to-skin contact), which have been shown to be individually analgesic, by allowing newborns to suckle their nursing mothers before, during, and after a standard heel lance procedure for blood collection. The efficacy of this intervention was determined by evaluating video recordings of infant crying and facial expressions and by assessing blockade of heart rate increases that normally accompany the blood collection procedure. Method: 30 healthy, term, breast-fed infants @ Boston Medical Center Hospital Randomized to breast-fed and control Heel lance performed while swaddled, with and without nursing Measured crying, grimace, heart rate

Results - Crying & Grimace

Results - Heart Rate

Pharmacologic Treatment Pharmacological analgesia should be chosen carefully based on comprehensive assessment of the neonate, efficacy and safety of the drug, the clinical setting, and experience of the personnel using the drug. Drug doses, including those for local anesthetics, should be calculated carefully based on the current or most appropriate weight of the neonate, and initial doses should not exceed maximal recommended amounts. Subsequent doses should be modified based on multiple factors, including the cause of the pain, previous response, clinical condition, concomitant drug use, and the known pharmacokinetics and pharmacodynamics of the sedative and analgesic drugs administered. Medications that might result in the loss of protective reflexes or cause cardiorespiratory instability should be used only by appropriately trained persons in an environment equipped to handle emergencies.

Continued Studies are lacking on the management of pain in neonatal conditions associated with extensive tissue damage and those resulting in recurrent or chronic pain (e.g., necrotizing enterocolitis, meningitis, fractured bones). The effects of the use of analgesics or sedation during the neonatal period on long-term neurodevelopmental and psychological outcomes has not been well studied.49 No differences in intelligence, motor function, or behavior at 5 to 6 years of age were found between neonates who received morphine for sedation during mechanical ventilation and placebo-treated neonates.62

A Simple Guideline

Potential Adverse Effects of Supportive Medications

Recommendations Pain in newborns is unrecognized and under-treated. Prescribe analgesia when indicated during their medical care. If a procedure is painful in adults, it should be considered painful in newborns, even if they are preterm. Newborns may experience a greater sensitivity to pain and are more susceptible to the long term effects of painful stimulation. Treatment of pain may be associated with decreased clinical complications and decreased mortality. Arch Ped Adoles Med Feb 2001

Recommendations The appropriate use of environmental ,behavioral, and pharmacologic Interventions can prevent, reduce or eliminate neonatal pain in many clinical situations. Sedation does not provide pain relief and may mask the neonate’s response to pain. Health care professionals have the responsibility for assessment, prevention and management of pain in newborns. Clinical units providing health care to newborns should develop written guidelines and protocols for the management of neonatal pain.

Thanks for Listening Because of you… Life is Good ! Thanks