How to Manage Acute Pain in Neonate and Infant

Elizeus Hanindito Dept. of Anesthesiology & Reanimation Medical Faculty of Airlangga University dr.Soetomo General Hospital SURABAYA

Definition of Pain

Nyeri adalah rasa inderawi dan pengalaman emosional yang tidak menyenangkan akibat adanya kerusakan jaringan yang nyata atau yang berpotensi rusak atau sesuatu yang tergambarkan seperti itu

Proportion of NICUs Treating Pain During Invasive Procedures *

* Pain management in NICU , Lago P. J Ped Anesthesia 2005

60% of adult patients in the ED received analgesia for burns & fractures compared with 28% of pediatric patients.
Selbst & Clark . Sedation & Analgesia in the ED 1990.

Pain is not recognized Misconception of pediatric pain Fear of respiratory depression & hypotension Fear of masking symptoms Unfamiliarity with analgesics,doses Inadequate training of medical professional

Common Misconceptions (Myths)

Myth 1 : the neural & endocrine systems of the newborn infant are not developed to the stage that allow for transmission of painful stimuli. That they cannot feel pain. Myth 2 : newborn infants cannot remember pain and therefore,there can be no sequelae. Myth 3 : pain cannot be assessed in the newborn infants. Myth 4 : newborn infants are easily comforted without analgesics.

Common Misconceptions (Myths)

Myth 5 : it is unsafe to administer opioids to infants and that infants often suffer respiratory depression following administration of opoids. Limited clinical information. Limited available research and acces.

Neonates experience pain even more than older infants !

Adaptive mechanisms do not develop until 32-36 weeks of postconceptional age

Why treat pain ?

Treatment & alleviation of pain are a basic human right !

regardless

of age

Fishman SM. Recognizing Pain Management as a Human Right: A First Step Anesthesia Analgesia 2007.

Neuroanatomy & Neurophysiology

Density of cutaneous nociceptive nerve endings ~ adults. Nociceptive tracts have completed by the end of third trimester. Substance P and its receptors are detectable in the fetal dorsal horn at 12 to 16 wks. Concentration of beta-endorphin increase in response to stress. A marked release of catecholamines, growth hormone, cortisol and glucagon occurs.
Andrews KA. The Human Developmental Neurophysiology of Pain. Pain in Infants,Children and Adolescents 2nd Ed 2003.

Short-term effects
Adverse short-term consequences:
Physiologic & biochemical sequelae: hyperglycemia,protein catabolism,oxygen consumption,gut motility,heart rate,blood pressure.
(Barker DP et al. Arch Dis Child Fetal Neonatal Ed. 1996; 75:F187)

Exposure of preterm neonates to repetitive pain and stress leads to clinical instability and complications
(KJS Anand. Crit Care Med 1993; 21: S358)

Long-term effects
Adverse long-term consequences:
Circumcision (without analgesia) increases pain response to subsequent vaccination
(Taddio A et al: Lancet 1997;349: 599)

Permanent structural and functional changes may occur in infants exposed to multiple painful and stressful events
(Porter FL et al: J Dev Behav Pediatr 1999;20:253)

Sustained physiologic,anatomic & behavioural changes result from repetitive or prolonged exposure to noxious stimuli.

Consequence

25 wk PCA

Full term Yes Yes

4-6 mo Probably ?

1-2 yr ? ?

4 yr ? ?

10 yr ? ?

Hyperalgesi : Sensitization: Physiologic destabilsation: Behavioural changes : Personality effects :

Yes yes

Yes
Yes ?

Yes
Yes ?

?
Yes ?

?
Probably Probably

?
Possibly Possibly

?
? Possibly

Anand KJ,Kenneth RG.Longterm Consequences of Pain in Neonates. Pain in Infants Children and Adolescents 2nd Ed 2003

Pediatric Pain Assessment

Pain management begins with an assessment of the child with pain . Not only the explicit pain features but also the situational factors that modulate pain-measurement of infant pain is just one aspect of comprehensive pain assessment. Pain is private & subjective, can only be accessed & measured by indirect method. Health care facilities now identify pain assessment as the 5th vital signs.
Gaffney A et al. Measuring Pain in Children: Developmental & Instrument Issues. Pain in Infants,Children and Adolescents 2nd Ed 2003.

Pediatric Pain Assessment

Behavioural parameters Physiological parameters Biochemical parameters Self-Reporting measures Unidimensional tool Multidimesional tool
Anand KJS.Pain and Pain Management during Infancy. Research and Clinical Forum 1998

Behavioural Parameters
Crying characteristics. Facial expressions. Simple motor responses. Complex behavioural responses. More specific and consistent than physiological measurements.

Facial Expression of Physical Distress

NASOLABIAL FOLD deepened

Physiological Parameters
Heart rate. Respiratory rate. Blood pressure. Objective, Palmar sweating. Precise , but Not specific for pain Vagal tone. Oxygen saturation. Transcutaneous O2/CO2. Intracranial pressure.

Biochemical Parameters
Catecholamines : Epinephrine, Norepinephrine. Cortisol : blood, saliva, or urine. b-Endorphin Growth hormone, glucose, glucagon, renin, aldosterone, and lactate have also been noted to increase with pain. Insulin secretion is usually suppressed.

Newborn Pain Assessment Tools

FLACC (Face,Legs,Activity,Cry,Consolability). PIPP (Premature Infant Pain Profile). CRIES (Crying,oxygen Requirement,Increased vital
signs,Expression and Sleeplessness).

NIPS (Neonatal Infant Pain Scale). N-PASS (Neonatal Pain Agitation and Sedation
Scale).

NFCS (Neonatal Facing Coding System).

Childrens Hospital of Eastern Ontario Pain Scale (CHEOPS)

Score Cry Facial Verbal Torso Legs

0 smile + neutral neutral

1 + composed shifting/tense kick/squirm

2 scream grimace pain complaint restraint restraint

Self-Report Measures
Self-report measures. Poker Chip Tool (Hester) Faces Scale (Bieri) Visual Analog Scale (VAS) Oucher Scale (Beyer & Wells) Pain Diary
Anne G,Patrick JM. Measuring Pain in Children:Developmental & Instrument Issues Pain in Infants,Chidren and Adolescents 2nd Ed 2003

Validity & Reliability

Validity :
the ability of the pain tool to measure pain as an isolated condition differentiated from other condition, such as distress and agitation

Reliability :
the tools ability to consistently score pain each time the tool is used (test-retest reliability) and when different people use the tool (interrater reliability).

Easy to administer at the bedside. appropriate for the gestational age.

Procedural Pain in NICU

> 10/day several hundred in the course of a prolonged admission. Procedural intervention :
* tracheal suctioning
* heel lancing * venepuncture * lumbar puncture * chest tube insertion * tracheal intubation
* Pain management in NICU , Lago P. J Ped Anesthesia 2005

Neonatal pain management

Prevention of pain is the best approach to pain management : * suctioning the infant on an as needed basis * limiting the number of painful procedure * skilled person to perform painful procedure * method by which we performs the procedure
(venipuncture vs heel stick)

Pharmacologic and nonpharmacologic approach.

Pharmacologic Intervention
Nonsteroidal antiinflammatory drugs. Intermittent/continuous narcotic. Patient-controlled analgesia. Peripheral nerve block. Regional anesthetic techniques.

American Academy of Pediatric,Canadian Paediatric Society,Committee on Drugs,Committee on Fetus and Newborn and Section on Anesthesiology Prevention and Management of Pain and Stress in the Neonate Pediatrics 2000

Nonpharmacologic Intervention
Oral sucrose,non-nutritional sucking Minimal handling protocols Lowering noise levels in NICU Avoiding exposure to bright lights Swaddling , nesting.

American Academy of Pediatric,Canadian Paediatric Society,Committee on Drugs,Committee on Fetus and Newborn and Section on Anesthesiology Prevention and Management of Pain and Stress in the Neonate Pediatrics 2000

Pain in pediatric trauma

Trauma Pediatric Morbidity & Mortality (USA : 500.000 hospitalization 15.000 20.000 deaths/year). Pain management :

* Emergency phase. * Healing phase. * Rehabilitation phase. The first priority is preservation of life and stabilization.
Rose JB. Pain Management for the Pediatric Trauma Revista Mexicana de Anestesiologia 2004

Ideal Analgesic in the ED

Rapid onset. Short duration of effect. Easily administered. Effective analgesia. Minimal side effects.

NSAIDs
Minimal sedation , emetic effect. Mild-moderate pain. Analgetic ceiling effect. Opioid sparing effect. Contraindication:
coagulation disorder. asthma. renal/liver disease.

NSAID Doses in Children

DRUG LOADING DOSE (mg/kg) MAINTENANCE DOSE (mg/kg) INTERVAL (hours) DAILY MAX DOSE (mg/kg)

Ketoprofen Ibuprofen Naproxen Diclofenac Ketorolac

2 10 10 2 0.5

1 10 5 1 0.25

6-8 6-8 8-12 6-8 6-8

5 40 15 3 2

Ketoprofen continuous : Loading dose 1 mg/kg in 15 minutes,infusion 3-5 mg/kg/24 h

Kokki H. Use.Abuse and Misuse of NSAIDS in Children European Journal of Anesthesiology 2005

Paracetamol Dosing in Children

Orally : 20 mg/kg loading dose. 15 mg/kg 4-8 hourly. Rectally : 30-45 mg/kg loading dose. 20 mg/kg 6-8 hourly. Maximum 90 mg/kg/day (neonate 60 mg/kg/day).

Ketorolac tromethamine
Effective for moderate postoperative pain. Has a significant opioid-sparing effect. Not recommended for < 1 year.

Recommended dosage & duration of ketorolac therapy in children

Intravenous : Initial dosage 0.5 mg/kg. Subsequent dosage 1.0 mg/kg q6h. I.V. infusion 0.17 mg/kg/h. Maximum daily dosage 90 mg. Maximum duration 2 days. Oral : Oral dosage 0.25 mg/kg q6h. Maximum daily dosage 1 mg/kg. Maximum duration 7 days.

Use of intravenous ketorolac in the neonate and premature babies. Papacci P et al. pediatric Anesthesia 2004.

Opioids
Morphine or Fentanyl most often used. Avoid Demerol (Meperidine) Requires frequent and thorough assessment of adequacy of pain relief and possible side effects < 6 months continuous respiratory monitoring: * < 1 month : 9 hours After the last administraton * 1-6 months : 4 hours

Estimated Values for Vd t1/2 CL of Morphine

Vd (L/kg) 2.8 + 2.6
2.8 + 2.6 2.8 + 2.6

Preterm
Term Infants & children

t1/2 (h) 9.0 + 3.4

6.5 + 2.8 2.0 + 1.8

CL (ml/min/kg) 2.2 + 0.7

8.1 + 3.2 23.6 + 8.5

Kart T, Lona L. Recommended Use of Morphine in Neonates,Infants and Children Based on Literature Review : Part 1 Pharmacokinetics. Pediatric Anesthesia 1997.

Morphine Dosing
Infusion : * 100 g/kg/hour for 2 hours. * Followed by 10-30 g/kg/hour. Intermittent Dosing : * 50-200 g/kg/dose i.v. slowly. * repeat as required usually 4 hourly. Fentanyl 1-2 g/kg/hour

Recommended Starting Setting for PCA in Children

Recommended drug concentration is morphine 1 mg/kg in 0.9% saline 50 ml. Bolus dose 0.02 mg/kg ; maximum 1 mg. Lock-out time 5-10 minutes. Frequency range 5 boluses/hour. Background infusion 4 ug/kg/h.

Opioids Side Effects

Morphine : Respiratory depression apnea Hypotension Urinary retension Fentanyl : Bradycardia hypotension Chest-wall rigidity Naloxone : 0.1-0.2/kg/dose (antidote)

Check patient before administering

Rousable to voice or light touch. Respiratory rate >20(infant) ,>30(neonate) Heart rate is appropriate.

Sedatives: benzodiazepines
Benzodiazepines : NOT analgesics. sedative-hypnotic, amnesic, anxiolytic, muscle relaxant, and anti-epileptic properties. Midazolam : short half-life and is approved by the FDA for neonatal use. Although an effective sedative, it can cause abnormal movements and adverse hemodynamic effects . Dose: 0.1 mg/kg IV over 5 min q2-4h. Can also be used continuous IV (10-50 mcg/kg/h), intranasal, sublingual, oral. Diazepam not recommended due to long half-life. Flumazenil 0.01 mg/kg/dose (antidote)

Precaution Needed for Use of Sedation/Analgesia in the ED

Appropriate personnel Monitoring Equipment Medication

Selbst SM,Zempsky WT. Sedation & Analgesia in the ED. Pain in Infants Children and Adolescents 2nd Ed 2003.

Caudal epidural analgesia

Most popular central block Easiest & safest approach Excellent analgesia-painfree awakening

Applicable to children of all ages

Caudal epidural catheter

Easier to place than lumbar Easily passed cephalad Never forcibly advance the catheter against resistance

Caudal Bupivacaine + Clonidine

1-2 ug/kg. Prolonged the duration of caudal block. Postoperative sedation + . Favorable analgesia-to-side effect profile.

Caudal Bupivacaine + Opioids

Morphine : 20-40 ug/kg ; 75 -100 ug/kg. Fentanyl : 0.5-1.0 ug/kg. Postoperative sedation + . Respiratory depression,nausea/vomiting, urinary retention.

Peripheral Nerve Block

Penile block. Ilioinguinal nerve block. iliohypogastric nerve block.

Brachial Plexus Block

Interscalene approach. Parascalene approach. Subclavian approach. Supraclavicular approach. Axillary approach.

Axillary approach