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Chapter 20

PAIN MANAGEMENT George A. Gregory, MD, Maurice Zwass, MD

INTRODUCTION

The International Association for the Study of Pain describes pain as, “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”1 Pain is sometimes beneficial (e.g., withdrawing a hand from hot stove), at other times it is detrimental (e.g., injury following burns, trauma, surgery) and can delay recovery from surgery, wound healing, and discharge from hospital. Pain can be acute (surgery, trauma, burn injury) or chronic (spine abnormalities, tumors, chronic infections). Anesthetists and surgeons are primarily concerned with the acute pain caused by surgery and trauma. Anesthetists are often asked to evaluate patients who have chronic pain and suggest possible therapy or provide treatment (including medical management as well as nerve blocks). It must be remembered that just because a patient cannot communicate her/his pain (infants, patients with cognitive disabilities) does not mean he/she is not having pain! Pain is subjective. What is not painful for one child may be very painful for another, based on previous experience with painful procedures (multiple IV insertions, surgeries), culture, and developmental stage. While consideration should be given to developing an acute and chronic pain clinics with people who are committed to reducing/eliminating pain, further discussion of doing so is beyond the scope of this chapter. For further information, several references have been included on how to establish these services.2,3 This chapter discusses development of pain pathways and the response of infants and children to pain. It also discusses detection, evaluation, and treatment of acute pain. The use of regional anesthesia for treatment of postoperative or chronic pain is discussed in Chapter 21.

As the American Academy of Pediatrics indicated in the year 2000, pain has immediate and long-term consequences in infants and must be prevented or, if it cannot be prevented, it must be treated effectively.4 Pain should be assessed before and after treatment to assure that the treatment provided (drug, dose, route) is effective. As far as possible, we have followed the World Health Organization (WHO) guidelines for treatment of pain. While the WHO’s guidelines are primarily for chronic pain (usually from cancer), this framework is useful for treatment of acute postoperative pain. whqlibdoc.who.int/.../9789241548120_Guid... There are many drugs available to treat postoperative pain, many of them with similar effects. Consequently, it is best to limit the number of drugs used by any clinic or hospital (or country) to a few drugs and be sure surgeons, anesthetists, and nurses are familiar with the drugs, their effects, the potential complications of using these drugs, and the treatment of any potential complications.

Chapter 20: PAIN MANAGEMENT

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Pain Pathways

Sensory receptors appear within the first few week’s of gestation, and integrated nociceptive cells (neurons that responds to potential tissue damage and send signals to the spinal cord and brain to perceive pain) are present by 24-28 weeks gestation and maybe earlier. There are cortical responses to noxious stimuli by at least 25 weeks gestation.5 Premature infants of 24 weeks gestation clearly respond to painful stimuli (heel stick) in the author’s experience. In fact, neonates born at 24-25 weeks gestation often exhibit exaggerated responses to stimuli (painful and otherwise), in part because brain-derived inhibitory pathways develop later.6 Consequently, the young infant’s response to pain is greater (more active) than in later life.

Ill babies requiring neonatal intensive care often undergo approximately 15 painful procedures every day, and these procedures have long-lasting effects. The repeated painful stimuli result in hyperalgesia (excessive sensitivity to pain) and increased responsiveness to pain and to touch (bathing, changing clothes and dippers). The hypothalamic-pituitary axis produces β endorphins in response to stress by 18 weeks gestation. Cortisol and noradrenaline are produced by 20 weeks gestation. The stress response has detrimental effects, but it is also necessary for maintenance of arterial blood pressure, cardiac output, and tissue oxygen delivery.

Most neonates respond to pain with increased heart rate, but very ill babies may develop bradycardia because illness decreases baroreceptors function. Their autonomic nervous system responds to pain with peripheral vasoconstriction (pale skin), duskiness, and cyanosis. In response to pain, their movements are disorganized; including splayed (spread out) fingers, extended arms and legs, frantic behavior, and jumpy movements. They frown, bring their eyebrows together, narrow or close their eyes, avoid eye contact, and sigh. Good evidence of pain in neonates is seeing their eyebrows go down and together, their nasal root (top of their nose where it meets the frontal bone) widen and bulge, their eyes close tightly, and their mouths become angular and squared (Table 20-1). In some cases they do just the opposite (they become completely limp).

Anesthesia Care of Pediatric Patients (George A. Gregory & Dean B. Andropoulos)

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Figure 20-1: Facial Response to Pain in Infants

See text for description. From Wong’s Clinical Manual of Pediatric Nursing. With Permission

Bartocci et al.7 reported that heal punctures significantly increased cerebral blood flow and oxygen delivery to the side of the brain being stimulated, while blood flow and oxygen to the other side decreased or did not change. The increase in flow was greater in males than in females, suggesting to some people that female babies felt pain less well than male babies. While this is not true, many nurses and doctors caring for neonates have administered less pain medication to female than to male patients for unknown reasons. Peterson et al.8 found a correlation between the smaller brain volumes of ex-premature infants and their cognitive and behavioral outcomes. These changes were most prominent in somatosensory cortex and in the thalamic and hypothalamic regions of the brain. There is however, variation in the anesthetic requirement with age Table 20-1.


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Table 20-1: Halothane requirement versus Age Age

MAC

≤33wks 0.55 ± 0.05 Term – 1mo 0.87 ± 0.03 1mo – 6mo 1.20 ± 0.06

wks = weeks; mo = months; MAC = minimum anesthetic concentration (alveolar concentration of halothane at which 50% of patients move and do no move with a skin incision.

Repeated neonatal pain increases the response to future injury. Circumcision without anesthesia significantly increases responses to vaccinations months or years later.9 Adequate anesthesia for circumcision ameliorates this response. Despite this knowledge, many infants still undergo circumcision without anesthesia. Children born with difficult births (forceps delivery, meconium) have increased pain responses as adults. Having a baby suck on a nipple containing sucrose reduces the response to heal stick but fails to prevent hyperalgesia later. There is still an increased stress response (cortisol release) to needle sticks at six months of age. Animals exposed to pain early in life had higher pain thresholds, impaired spatial learning, and exaggerated startle responses.10 Acute pain causes the release of catecholamines, corticosteroids, glucagon. It also causes breakdown of fat and carbohydrates (stress response);11 and stimulation of heart rate, arterial blood pressure, and respiratory rate, although many babies respond to pain by reducing respiratory rate and arterial blood pressure. Some babies appear to be “catatonic”. In fact, some ex-premature infants have reduced pain later in life. Hypersensitivity may be the reason premature infants required higher levels of analgesia and anesthetics for sedation than term neonates. Increased sensitivity plus lack of inhibition may cause windup [i.e., an increase in pain strength following repeated painful stimuli (e.g., heel stick)]. Windup is thought to be the result of repeated stimulation of C fibers in the spinal cord posterior horn.12 Premature infants who have repeated painful procedures may have inhibited brain growth and development.

Classification of Pain

Pain is classified in many ways. In this chapter it is primarily defined pathologically, i.e., as nociceptive and neuropathic (Table 20-2). Nociceptive pain occurs when nociceptors (pain receptors that respond to noxious stimuli) are stimulated by tissue injury. These stimuli include temperature (heat, cold), vibration, stretch, and chemical compounds released by hypoxia, acidosis, and inflammation. The pain is said to be either somatic or visceral, depending on where the pain arises. Somatic pain is usually the result of activation of skin, mucosa, bones, joints, muscle, and connective tissue. Visceral pain arises from organs within the chest and abdomen.


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Table 20-2: Differentiating Features of Nocioceptive and Neuropathic Pain13 Types of Pain

Origin of Stimulus

Localization Character Referral and radiation of pain/sensory dysfunction

Examples

Nociceptive pain Superficial somatic pain

Arises from nociceptors in skin, mucosa of mouth, nose, urethra, anus, etc. Nociceptive stimulus is evident

Well localized

Usually sharp and may have a burning or pricking quality

None • abscesses • postsurgical pain from a surgical incision • superficial trauma • superficial

Nociceptive pain Deep somatic pain

Arises from nociceptors in bone, joint, muscle and connective tissue. Nociceptive stimulus is evident

Usually well Localized with tenderness to palpation

Usually dull or aching or throbbing in quality.

In some instances, pain is referred to the overlying skin. No associated sensory dysfunction.

• bone pain due to metastasis • fractures • muscle cramps • sickle cell vasoocclusive episodes

Nociceptive pain Visceral pain

Arises from nociceptors in internal organs such as the liver, pancreas, pleura and peritoneum.

Poorly localized, diffused. Palpation over the site may elicit an accompanying somatic pain.

Usually vague, dull, aching, cramping or tightness, deep pressure, spasms, or squeezing or colicky in nature. Nausea, diaphoresis and emesis are frequently present.

In some instances, pain referred to skin supplied by same sensory roots that supply the diseased organ. There may be radiation of the visceral pain, but it will not be in a direct nerve distribution. No associated sensory dysfunction.

• pain from acid indigestion or constipation • pain due to stretching from liver metastasis, pleura stretching due to pleuritis, as in pneumonia or tuberculosis


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Table 20-2 (continued) Neuropathic pain

Is generated at various sites, and is not always stimulus dependent.

Poorly localized, diffuse pain in an area of sensory dysfunction in the area of anatomical distribution of nerve supply.

Difficult to describe and different words may be used in different populations: • burning, pricking or needle like pain; • sharp or shooting. The pain may be persisting or recurrent.

Neuropathic pain is perceived within the innervation territory of the damaged nerve. There may be abnormal radiation. The pain is associated with sensory dysfunction (dysesthesia, hypoesthesia, hyperesthesia, allodynia).

• central neuropathic pain due to spinal cord injury from trauma or tumour • painful peripheral neuropathies, due to HIV/AIDS, cancer or anticancer treatment pain (e.g. chemotherapy with vincristine) • phantom limb pain

From Ref 13. WHO. With permission.

Neuropathic pain, on the other hand, arises from nerve cell injury in the peripheral or central nervous system. It can be the result of trauma, tumors, infections, and inflammation. Fortunately, the common causes of neuropathic pain in adults (diabetic neuropathies, post-herpetic neuralgia, and trigeminal neuralgia) are uncommon in children. Table 20-3 lists the common features of neuropathic pain.


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Table 20-3: Common Sensory Features of Neuropathic Pain13 Alodynia Pain due to a stimulus that normally does not provoke pain (touch, clothing) Hyperalgesia Increased pain response to a normal painful stimulus (tactile or thermal (both

are rare). Hyperalgesia to cold is more common than to heat Hypoalgesia Diminished pain response to a normally painful stimulus (tactile or thermal,

both are frequent). Paresthesia Abnormal sensation to a stimulus that is normally not unpleasant, such as

tingling, pricking or numbness. It may be spontaneous or evoked.

Dysesthesia Unpleasant sensation. It may be spontaneous or evoked.

Hyperesthesia Increased sensitivity to stimulation (tactile or thermal, both are rare). Hypoesthesia Decreased sensitivity to stimulation (tactile or thermal, both are frequent).

From REF 13. With Permission: WHO

Mixed pain occurs when both neuropathic and somatic pain are present at the same time (e.g., burns).

Pain can also be defined as acute or chronic. Acute pain is of sudden onset, severe in intensity, and lasts less than 30 days (most surgical pain). Chronic pain, on the other hand, is either continuous or recurrent and last more than 30 days. Chronic pain wears on the patient and affects her/his activities, including school, playing, and family interactions. It also interferes with a child’s ability to work and help support her/his family. Children with chronic pain are often depressed, are chronically fatigued, irritable, occasionally seek drugs (pain medications), and can exhibit problems with relationships.

Despite appropriate pain treatment, patients sometimes have intermittent increases in pain so called breakthrough pain (a temporary increase in pain beyond that which is present at baseline). When this occurs, it is usually necessary to increase the dose of her/his usual pain medications. It is important to have in place plans for giving additional doses of medication for management of breakthrough pain so the patient is not left with pain until he/she can contact someone. The patient should be told what to do (how much to increase her/his pain medications over and above the usual doses or whether he/she should take another pain medication in addition to her/his usual drug). Breakthrough pain is often treated by administering additional pain medication (often 10% of the daily dose). It is important to differentiate break through pain from end of therapy pain, which occurs at the time the effects of the patient’s usual drug dose is


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wearing off and he/she would normally take her/his usual dose of medication for pain. There is no need to increase the dose of drug in this situation. When patients who have pain must do something that will increase their pain (move, walk, climb stairs, physical therapy) it is important to give an additional dose of pain medication before this activity takes place.

Evaluation of Pain in Children

Evaluation of pain is often more difficult in children, especially young children, because they are unable to communicate the location, type (sharp, dull,) or whether anything makes the pain worse or better. As with all pain in young children, the parents can be the best source of information. Parents frequently can best interpret their child’s pain when their child cannot do so.

Evaluation of pain in children begins with a comprehensive history (from the child if possible and from the parents/caretaker) and a complete physical examination. The history should include defining the word(s) used by the patient and family for pain. These words should be used when discussing pain with the child or family. How does the child respond to pain? Is it by withdrawing, crying, moving frantically, or in other ways? What makes the pain worse (movement, touching, clothing, hot or cold food or drink)? What makes it better? Does heat, cold, not moving, eating specific foods (milk) make it better? Has the family given the child medication for pain? If so, what medications were given? What doses were given? Sometimes parents tend to give more than appropriate amounts of medication to treat their child’s pain. If so signs of drug toxicity should be sought. What was the response to the drugs given for pain? Did they improve/eliminate the patient’s pain.

There are many methods of evaluating how much pain a patient is having, although these methods may not work well in children if they cannot communicate their symptoms effectively or at all. Table 20-4 provides information regarding how infants and children express pain.


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Table 20-4: Expression of Pain by Infants and Children Age

Response to Pain

Infant Facial expressions (See above), rigid body, arching of back, arms and legs extended, legs drawn up, crying/screaming, irritable, difficulty sleeping

Toddler (1-3yrs of age)

Loud mad cry, angry, withdrawn, guards painful area, difficulty sleeping

Preschool (3-6yrs)

Verbalizes pain, thrashes about in response to pain, pushes people away, clings to family and others, sleeplessness

School age Verbalizes pain, nightmares, stalling behavior (e.g., “wait a minute”), rigid muscles, gritted teeth, closed eyes, frown, sleepless

Adolescent Localize and verbalize pain, may deny pain around peers, sleeplessness, muscle tension, body control

Modified from Mazur A, Winnicki IR, Szxzepanski T. Pain Management in Children. Ann Agric Environ Med 2013;1:28-34.

Pain Assessment

There are multiple ways to assess pain in infants and children. Table 20-5 is a very useful table from the WHO that lists appropriate questions to ask.13


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Table 20-5: Questions to be Asked of Children and Parent About Pain13 Questions to be Asked by Health Care Providers

What words does the child and family use for pain? What verbal or behavioral cues does the child use to express pain? What do the parents and/or caregivers do when the child has pain? What works best in relieving pain? Where is the pain and what are the characteristics (sites, severity, character of pain as described by the child/parent, e.g., sharp, burning, aching, stabbing, shooting, throbbing? How did the present pain start (was it sudden/gradual)? How long has the pain been present (duration since onset)? Where is the pain (single/multiple sites)? Is the pain disturbing the child’s sleep/emotional state? Is the pain restricting the child’s ability to perform physical activities (sit, stand, walk, run)? Is the pain restricting the child’s ability/willingness to interact with others, and ability to play?

From WHO with permission

A child’s ability to express pain is dependent on several things, including age, cognitive development, and cultural beliefs. Patients who are taught to be stoic may have significant pain and not express or be reluctant to express it because they were taught not to and that doing so is viewed as a sign of weakness. Most 2-4 year old children can verbally describe pain. By five years, they can describe pain and its strength (severity). By six years, they can differentiate levels of pain. By 7-10 years they can explain why something hurts.14

Clinically observing the patient in her/his response to pain is important. As stated in reference 13, the main behavioral responses to pain are:

• Facial expressions • Body movement and body posture • Inability to be consoled • Crying • Groaning, moaning


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Their response to pain includes:

• Abnormal posturing • Fear of being moved • Lack of facial expression • Lack of interest in surroundings • Quietness • Increased irritability • Sleep disruption • Anger/fear • Change in appetite • Poor school performance

However, as the American Society of Pediatrics stated in the year 2,000, patients who do not show signs of pain may still have significant pain.4 The presence or absence of pain must be determined individually in every patient. It is also important to determine the patient’s nutritional state. Children with poor nutrition may not respond to pain because they are under stimulated and/or developmentally delayed.

Tools for Measuring Pain

Methods (tools) have been developed to measure how much pain a patient is having. It is important to choose and use tools that are appropriate and easy of use in the society for which they are being used. They must also be appropriate for the child’s age. One or two pain tools should be chosen and used so that nurses, parents, anesthetists, and surgeons become very familiar with their use. Two of these are the Wong’s Pain Scale (Figure 20-2) and the Visual Analog Scale (Figure 20-3).

Figure 20-2: Wong-Baker Pain Scale for Infants and Young Children

The faces are shown to the child and he/she is asked to show which face most shows how they feel. Wong’s Essentials of Pediatric Nursing. With permission


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The Wong-Baker Scale is widely used, has been translated into many languages, and is easy to use. It was designed for children three years of age and older. The scale is used by having someone point to each face and describing to the child the pain intensity shown on each face. Then the child is asked to point to the face that best describes her/his own pain. The first face is described as no pain; each subsequent face is described as hurts a little more than the previous face until number five is reached. The fifth face is described as “hurts as much as you can imagine”.

The Visual Analog Scale is another scale that is widely used for patients who are 7-8 years of age and older, including adolescents and adults. The scale, which consists of a straight line that is divided into 10 equal parts (Figure 20-3), has been translated into at least 12 languages. The results correlate significantly with the patient’s and caregiver’s rating of the child’s pain. It is easy to use and is reproducible.

Figure 20-3: Visual Analog Scale

From: www.cancer.gov. The Visual Analog Scale is used by telling the child that zero (0) represents no pain. Five (5) is moderate pain, i.e., there is some pain but he/she can live with it. Ten is the worst pain possible. The child is then asked to point to or say what number is consistent with her/his pain. The scoring should be done before treatment and 30 minutes after treatment of the pain to be sure he/she is receiving adequate pain relief. If not, other treatment (medications) will be required.

Using these scoring systems allows for easy, repeated determinations of the child’s pain and whether the treatment provided is effective or not. These are not linier scales, so four does not mean the pain is twice as severe as a score of two or that two is half of four. It does mean that the pain at four is greater than at two. The scores may be affected by outside factors (malnutrition, degree of illness, etc.). Doing the measurements at the same time each day and recording the scores, pain location, and what makes it better or worse makes it easier to determine the pain pattern and whether the treatment is effective.

Treatment of Pain

Regional anesthesia effectively treats and prevents pain. This is discussed in Chapter 21 and will not be discussed further here.


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The basic principles for treatment of postoperative pain include, non-pharmacologic (distraction, placing the patient in the most comfortable position, swaddling of infants, preventing patient movement) and pharmacologic methods.

It is often best to use analgesic drugs that can be given by more than one route (oral, intravenous, subcutaneous, rectal, nasal). Intravenous or intramuscular (IM) administration of medication is the most common methods of treating postoperative pain on day one after surgery; oral drugs are commonly used thereafter. However, IM injections are painful, especially in the small muscle of infants. Clinicians should choose the most effective and least painful routes for administration of analgesics. Much higher doses of drugs are required (e.g., acetaminophen 40mg/kg as initial dose) are required to achieve adequate serum levels with rectal administration because the bioavailability of the drugs is poor by this route and because the drugs are differentially absorbed. Rectal administration of pain drugs provides only sporadic pain relief. Intramuscular and subcutaneous injections are usually avoided because they cause added pain and can sometimes cause painful sterile abscesses. Drugs given by the nasal route often cause burning and pain due to their pH (midazolam, ketamine, fentanyl). However, intranasal fentanyl may be useful for the rapid treatment of uncontrolled pain. Oral administration of analgesics is the most acceptable rout for medicating children. If an IV is already in place, many drugs can be given intravenously. IV administration of drugs assures that the entire drug dose gets into the blood stream. Drugs given orally, on the other hand, are absorbed to varying degrees. Once absorbed, as much as 50% of the drug absorbed from the stomach can be metabolized in the liver before it gets to the central circulation (midazolam). Thus, the effective dose is only one-half of that given. This is why larger doses of drug are required to get the desired effect.

WHO recommends treatment of pediatric pain by:13

• Using the two step method • Dosing the drug at regular intervals, not just when the patient is having pain • Using an appropriate and effective route of administration • Adjusting treatment to the individual patient

The two-step approach to the treatment of pain was originally devised by the WHO for the treatment of chronic pain (e.g., cancer pain) but has been widely and effectively adapted for use with acute postoperative pain. This will be followed in the remainder of this chapter because their document is widely available.13 Pain is divided into mild (step 1) and moderate/severe (step 2) pain, and the therapy provided is based on the degree of pain.

Step one provides treatment for mild postoperative pain (Table 20-6). Medications used in this step include prostaglandin synthetase inhibitors (acetaminophen, acetylsalicylic acid) and non-steroidal anti-inflammatory agents (NSAID – e.g., ibuprofen). It is often useful to use one of these drugs, e.g., ibuprofen, as the primary treatment for pain and another one, e.g., acetaminophen,


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for break through pain when it occurs. Effective postoperative pain relief requires that pain medications be given around the clock, i.e., on a schedule every four or more hours apart, depending on the age of the child and the half-life of the drug. If we wait for the child to complain or demonstrate signs of pain, it is too late. With fixed interval dosing, pain scores are lower and the overall dose of narcotic (when used) is less. For children who can take medications orally, paracetamol (acetaminophen) 15mg/kg and ibuprofen 5-10mg/kg/dose every 6-8 hours are the drugs of choice. For younger children who are three months of age and older, a liquid form of these drugs is available that is easily swallowed. The maximum dose per day is 40mg/kg. Only paracetamol is available for patients less than three months of age. Like all drugs, paracetamol and ibuprofen have potential toxicity, which include gastrointestinal bleeding, and renal failure with ibuprofen and liver failure with paracetamol. Consequently, these drugs should be given cautiously to patients who have bleeding difficulties or renal and/or liver problems. These serious complications are infrequent when the drugs are given over the amount of time required for surgical and trauma pain, and if they are given in the appropriate doses, especially in children. The most common cause of liver failure from acetaminophen is an overdose of drug that occurs when a child ingests an overdose of the drug at home, not in hospital.

Table 20-6: WHO Recommended Initial Doses of Non-Opioid Analgesics15 Drug

Neonates 0-29 days

Infants 30d to 3mo

Infants 3mo to 12mo

Maximum daily dose

aParacetamol 5-10mg/kg every 6-8hrs

10mg/kg every 4-6hrs

10-15mg/kg every 4-6hhrs

4 doses per day

Ibuprofen 5-10mg/kg every 6-8hrs

Child 40mg/kg/day

aOver two years of age, a dose of 15mg/kg (maximum 40mg/kg) can be given every six hours.

Step two provides treatment of patients with moderate or severe pain when paracetamol and/or ibupropfen do not completely relieve their pain. When this occurs, clinicians should consider administering narcotics to treat the patient’s pain. Narcotic administration alone is more likely to cause unwanted complications (hypoventilation, apnea, itching, vomiting, nausea). To reduce the dose of narcotic used and still provide adequate pain relief, it is often useful to combine narcotics with paracetamol or ibuprofen. This reduces unwanted complications, but does not totally eliminate them. One regimen gives the dose of narcotic and then gives the dose of paracetamol or ibuprofen about two hours later. Remember not to exceed the maximum doses of either paracetamol or ibuprofen. Table 20-7 gives the starting doses of two common narcotics. If these starting doses do not relieve the patient’s pain, the dose of drug is increased in a stepwise manner until her/his pain is relieved. In the end, the appropriate dose of narcotic is the one that effectively relieves the patient’s pain without causing unwanted side-effects. While the WHO


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states that “there is no upper limit” on narcotic dose, it is important to be cautious and watch for opioid related side-effects such as respiratory depression and not to administer enough narcotic to cause severe adverse conditions. (See below). We agree that the appropriate dose is that which relieves the child’s pain but still does not result in adverse side-effects. Giving enough narcotic to completely eliminate all pain may result in apnea and bradycardia. When administering narcotics, it is important to repeatedly evaluate patients for side effects. It is important to educate the parents about what side effect to look for and have them assist in the ongoing monitoring of the child, especially in countries that have few nurses and little technology. It is also important to determine if the patient has previously used pain-relieving medications, especially narcotics, because those who are narcotic naive may metabolize the drug more slowly and have a more profound response to the drug, including respiratory depression and apnea. It is often appropriate to intravenously administer half the usual dose of narcotic and determine its effect. Is the pain relieved? Is there evidence of hypoventilation? Fear that patients and hospital personnel will become addicted to narcotics is a common reason why narcotics are unavailable or avoided in some countries. Treating patients who have pain postoperatively with narcotics for several days does not lead to narcotic addiction, especially with morphine use.

Table 20-7: WHO Recommended Starting Doses of Narcotics for Infants.15 Medication Route of

Administration

Starting Dose

Morphine IV, SQ 1-6mo: 25-50mcg/kg/dose every 4-6hrs Fentanyl IV 1-2mcg/kg/dose every 2-4hrs

IV = intravenous; SQ = subcutaneous; hrs. = hours; mcg = micrograms. Narcotics should be administered slowly over several minutes while observing the patient’s respiratory rate and response to pain.

Two narcotics (fentanyl and morphine) are readily available in many countries for relief of postoperative pain (Table 20-7). Both effectively relieve severe pain, assuming the dose of drug given is adequate. Fentanyl is commonly used in Post Anesthesia Recovery Rooms (PACU) and the Intensive Care Unit (ICU) for acute treatment of pain, while morphine is used for longer-term treatment once the patient has left the PACU and ICU. Methadone, when available, may be a good choice of narcotic for longer-term use because its pain relieving effects last about 12 hours, and the same doses can be given orally and intravenously. Due to its longer half-life, methadone administration reduces the variation (peaks and valleys) in pain each day. Methadone also causes less respiratory depression than other potent narcotics.

Morphine is a very effective, inexpensive, widely available narcotic. However, in some countries its use is very tightly controlled. One of its main advantages is that it can be administered by multiple routes, including IV and by mouth (Tables 20-8 and 20-9). It can also be administered by continuous infusion. However, when given by continuous infusion, a properly calibrated infusion pump must be used. This reduces the chances that the patient will receive an inadvertent


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overdose of narcotic. Consideration for ICU or monitored room administration is wise with trained nurses so resuscitation can begin immediately if the patient develops apnea. The response to morphine is also age dependent. Neonates and young infants have immature enzyme systems for metabolizing morphine. By six months of age these enzymes are usually present at adult levels, unless the child was born prematurely. Maturity of these enzyme systems affects how often narcotics can be given. In 1-10 year olds, morphine is given every four hours; in 1-3 month olds it is given every six hours; in newborns it is sometimes only required once or twice a day. If a child is malnourished or has liver or kidney dysfunction, drug clearance may be slower, and the time between narcotic doses may have to be increased.

Remember, it usually takes about five drug half-lives to reach a steady state. (A half-life is the amount of time needed for the concentration of a drug to decrease to half its initial value). For morphine, the half-life is about three hours. Thus, it takes about 15hrs for a steady state to be reached. Administering the drug every four hours is usually sufficient to attain adequate blood levels after the child is one year of age. Patients may require a higher or more frequent dosing of morphine the first day after surgery, due to pain intensity. Children who are having significant pain seldom are sedated or have respiratory depression. Only when their pain is well controlled (abolished) do these problems occur. Consequently, the goal of pain control may not be the complete abolition of pain (a pain score of zero). There may be increased safety with scores of 1 – 3. A realistic goal for optimal pain control is to give that amount of medication that optimizes analgesia and functional activity of the patient. Using adjuvants facilitates pain relief and reduces the amount of narcotic required. The latter reduces the incidence of narcotic side effects.

Fentanyl is commonly used for acute treatment of pain, but because of its short half-life, it must be given every 45-60 minutes or must be given by continuous infusion to provide adequate pain relief. Fentanyl is very helpful for treatment of pain in an ICU or the PACU, but is not a good choice of narcotic for long-term treatment of pain on the ward.

Pethidine (meperidine) is available in some countries but should be used with caution because it is metabolized to normeperidine, which can be neurotoxic and may cause seizures. If pethadine is the only narcotic available, then it should be used to treat moderate and severe pain. Otherwise there are better choices.

Oxycodone and hydromorphone are useful drugs for treatment of long-term pain but usually are not optimal for the first few days after surgery (unless the surgery is minor). Once the acute phase of surgical recovery has passed (3 -4 days), these drugs can be used effectively to treat pain, often when given in combination with NSAIDS. While oxycodone is the active agent in the drug that relieves pain and does not have to be metabolized to morphine, it has a metabolite (oxymorphone) that is active. It is excreted in part by the kidneys and can accumulate in blood and tissue in patients with renal failure.


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All narcotics have side effects, including potentially causing excessive sedation without providing adequate pain control. Narcotics also cause nausea and severe itching. This problem of over sedation without adequate pain relief is often treated by reducing the dose of narcotic and by adding another drug (e.g., NSAIDS) to improve pain relief. Both nausea and itching associated with opioid administration can be treated by a reduction of dosage and sometimes by continuous infusion of low-dose naloxone. It is necessary to give naloxone by continuous infusion because the half-life of the naloxone is much shorter than the half-life of narcotics such as morphine. Also, with a continuous infusion, it is possible to titrate the dose of naloxone so that unwanted narcotic side effects are relieved and still not take away the patient’s pain relief. The starting dose is usually 0.5mcg/kg/hr.; the dose is increased progressively to 2mcg/kg/hr. in 0.5mcg/kg/hr. steps if necessary. Naloxone is placed into a known volume of fluid (e.g., 2mg naloxone mixed in 250ml of NS) and run at the above infusion rates. If available, it is better to use an infusion pump to assure constant drug infusion. If the infusion rate is too high, the patient will have severe pain because naloxone will reverse the pain relieving effects of the narcotic. If morphine is being infused continuously, naloxone can be added to the morphine infusion, and the two drugs can be infused jointly. However, this requires determining the effective dose of naloxone and adding enough naloxone to the morphine solution to relieve the itching and nausea without removing pain relief. When the two drugs are mixed together, it is difficult to change the concentration of either drug without making a new mixture, which may be wasteful. Diphenhydramine (Benadryl) is not a good choice for the treatment of itching, since only 10% of itching from morphine and 0% from Fentanyl is due to histamine release.

Treatment of nausea is a complicated because nausea can be caused by five different receptors. Finding the right drug (other than naloxone) to treat the specific cause in a give patient is often by trial and error, i.e., multiple drugs must be tried until one is found that treats the problem. Nausea can sometimes be treated with Ondansetron (4-8mg)) or with metaclopromide (0.1-0.2mg/kg/dose every 6-8hrs). Children over 14yrs of age can receive 10mg total every 6-8hrs. Some patients respond to low-dose benzodiazepines, but these drugs also cause sedation. If sedation is not particularly desired, benzodiazepines may be a poor choice for the treatment of nausea.


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Table 20-8: WHO Recommended Starting Narcotic Doses for 1 month to 1-Year Old Children15 Medication Route of

Administration

Starting Dose

Morphine Oral (immediate release) IV or SQ IV infusion IV injection and SQ IV infusion

80-200mcg/kg every 4hrs 1-6months - 100mcg/kg/every 6hrs 6-12months – 100mcg/kg/every 4hrs (maximum dose 2.5mg/dose 1-6 months – initial dose 50mcg/kg then 10-30mcg/kg/hr. 6-12 months – initial IV dose 100—200mcg/kg then 10-30mcg/kg/hr. 25-50mcg every 6hrs 1-6mo initial dose 50mcg/kg then 10-30mcg/kg/hr. 6-12mo initial dose 100-200mcg/kg then 20-30mcg/kg/hr.

Fentanyl IV Injection IV infusion

1-2mcg/kg every 2-4hrs Initial IV dose 1-2mcg/kg, then 0.5-1mgc/kg/hr.

Oxycodone Oral 50-125mcg/kg every 4hrs

IV = intravenous; SQ = subcutaneous; mcg = micrograms; kg = kilograms; hr. = hour; mo. = month


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Table 20-9: WHO Recommended Starting Narcotic Doses for 1-12 Year Old Children15 Medication Route of

Administration

Starting Dose

Morphine IV Subcutaneous Oral Infusion

0.1-0.15mg/kg every 4 hours 0.1-0.2mg/kg every 4 hours – maximum dose 2.5mg 0.2-0.4mg/kg every 4 hours Initial dose 0.1mg/kg then 0.1-0.2mg/kg/min – maximum dose 2-2.5mg

Fentanyl IV IV infusion

1-2mcg/kg every 30-60 minutes Initial dose 1-2mcg/kg then 1mcg/kg/hr.

aMethadone IV and subcutaneous Oral

0.1mg/kg every 4 hours for first two doses then every 6-12 hours. 0.1mg/kg every four hours for the first two doses and then every 6-12 hours

Hydromorp-hone

IV or SQ injection Oral

0.15mg/kg every 3-6 hour 30-80mcg/kg every 3 hours – maximum dose 2mg/dose

Oxycodone Oral

0.125-0.200mg/kg every four hours – maximum dose 5mg/dose

a dose of methadone is the same for all routes of administration. These are starting doses. They may have to be increased as needed to treat the patient’s pain. IV = intravenous; mcg = micrograms; SQ = subcutaneous

Codeine is not recommended for use with children because of their varied response to the drug. About 10-15 percent of people (children and adults) lack the liver enzymes required to metabolize codeine to morphine (which is the primary source of pain relief with this drug). Failure to metabolize codeine to morphine prevents the drug from providing pain relief beyond that of the drug with which it is mixed (paracetamol, ibuprofen). On the other hand, some people (including children) are hyper metabolizers of codeine and much more rapidly convert codeine to morphine resulting in rapidly elevated morphine blood levels. This has caused respiratory depression, apnea, and death in some children.16,17,18 Furthermore, for the first five years of life, children have only about 25% of the amount of the enzyme (CYP2D6) they have later in life. Thus, most children convert much less codeine to morphine and get much less pain relief form the drug. This also means that all drugs (codeine, tramadol, dihydrocodeine) that require conversion of the drug to morphine or another active ingredient for pain relief will not be as effective in children who lack this enzyme for drug conversion. This is why the WHO suggests morphine as the drug of choice for pain relief. Morphine’s effects are well known, does not have to be converted to another drug to relieve pain, and is inexpensive.


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Tramadol is also used for treatment of acute pain. It has two actions: 1) it acts as a weak narcotic and 2) it inhibits reuptake of serotonin-norepinephrine. The half-life of tramadol is 6-7hrs; its active metabolites have half-lives of 10-11hrs. Like many other drugs, the kidneys excrete one of the active metabolites. Consequently, renal insufficiency or failure prolongs its effects. The usual dose of tramadol is 0.5 – 1mg/kg every 3-to-4 hours (maximum dose 50mg/dose). It is often combined with other drugs (paracetamol) to improve its pain relieving characteristics. The pain relieving effects of tramadol last about six hours. Tramadol is thought to be about as effective as morphine for the treatment of moderate pain. The drug is only available in oral and IV forms. The complications associated with tramadol are considered minor and include nausea, dizziness, dry mouth, abdominal pain, vomiting, constipation, and drowsiness. Respiratory depression and constipation occur less often than with other narcotics. Since its metabolism depends on the CYP2D6 enzyme and several others, it should be used with care in patients who lack this enzyme or who are thought to be hyper metabolizers. Patients who lack CYP2D6 will get less pain relief from the drug. Pain relief can be improved by increasing the dose of the drug by about 30%. Since the kidney is responsible for removing a significant amount of the drug from the body, renal insufficiency or failure may affect dosing.

All narcotics should be used with care, and attempts should be made to prevent complications when possible. Monitoring the patient for drug side effects is the only way to determine the presence of potential complications.

Tolerance to the effects of narcotic may occur, especially to fentanyl. The dose that is effective today may not be affective tomorrow or the day after. This must be taken into account, and the patient must be evaluated several times a day to ensure he/she is still getting pain relief from the dose of drug being given. If this is not the case, it is often necessary to increase in the dose of drug administered. If the narcotic is suddenly withdrawn (especially fentanyl), the patient may show signs of drug withdrawal, including irritability, anxiety, sleeplessness, increased muscle tone, nausea, vomiting, diarrhea, and loss of appetite. Children undergoing withdrawal can also have evidence of tachypnea, tachycardia, fever, sweating, and hypertension. Such patients are often inconsolable.

What should we do if the patient receives an overdose of narcotic? As in all resuscitations, Airway, Breathing, and Cardiac support are the first steps See Chapter 5). Oxygen administration and ventilation of the lungs with a bag-and-mask are immediately provided. If there is severe bradycardia, it may be necessary to administer atropine 30mcg/kg (maximum dose 1mg) or to perform closed chest cardiac massage. If respiratory depression or apnea occurs, naloxone 10-20mcg/kg is given and its effect evaluated. The dose is increased by 1mcg/kg every three minutes until spontaneous breathing is resumed. Breathing usually returns before the withdrawal syndrome or lack of pain relief occurs. Once spontaneous breathing has resumed, it is necessary to infuse low dose naloxone to sustain breathing. Remember, the half-life of naloxone is much


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shorter than the half-life of most narcotics. Consequently, it may be necessary to infused naloxone for several hours.

Summary

Pain is common, especially following surgery. It is incumbent on everyone caring for children to assure that the child’s pain is adequately treated and that he/she is comfortable. For mild pain acetaminophen and ibuprofen are the first line drugs. For moderate and severe pain, morphine and fentanyl are appropriate drugs, with or without acetaminophen and/or ibuprofen. When narcotics are given, the patient must be monitored for hypoventilation or apnea. If either occurs naloxone administration is small doses is appropriate, but it must be given by IV infusion or by the anesthetist sitting with the patient and administering intermittent doses that are sufficient to allow normal breathing without taking away the patient’s pain relief. Positioning the patient, massage, and distraction may reduce the pain. In some countries acupuncture or acupressure may effectively relieve pain.

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3. Kopf A, Patel NB. Guide to Pain Management in Low-Resource Settings. International Association for the Study of Pain.

4. American Academy of Pediatrics. The Assessment and Management of Acute Pain in Infants, Children, and Adolescents. Pediatrics 2000;108:793-797

5. Fitzgerald M. The development of nocioceptive circuits. Nat Rev Neurosci 2005;6:507-520 6. Hathaway GJ, Vega-Alvelado D, Fitzgerald M. A critical period in the supraspinal control of

pain: opioid-dependent changes in brainstem rostroventral medulla function in preadolescence. Pain 2012;153:775-83

7. Bartocci M, Bergqvist LL, Lagercrantz H, Anand KJ. Pain activates cortical areas in the preterm newborn. Pain. 2006;122:109-117

8. Peterson BS, Vohr B, Staib LH, Cannistraci CJ, Dolberg A, et al. Regional brain volume abnormalities and long-term outcome in preterm infants. JAMA 2000;284:1939-47

9. Taddio A, Goldbach M, Ipp M, Stevens G, Koren G. Effect of neonatal circumcision on pain responses during vaccination in boys. Lancet 1995;345:291-92

10. RenK, Anseloni V, Zou EB, et al. Characterization of basal and re-inflammation-associated long-termalsteration in pain responsivity following short-lasting neonatal local inflammatory insult. Pain 2004;110:588-96


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11. Anand KJ, Sippell WG, Aynskey-Green A. Randomized trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response. Lancet 1987;1(8527):243-8

12. (Feng Xu; Tianjian Lu (29 May 2011). Introduction to Skin Biothermomechanics and Thermal Pain. Springer. p. 347. ISBN 978-3-642-13201-8. Retrieved 20 July 2014.)

13. WHO Guidelines on the Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses. World Health Organization. Geneva 2012

14. McGrath PJ, Craig KD. Development and psychological factors in children’s pain. Paediatric Clinics of North America. 1989;14:21-26

15. Mazur A, Winnicki R, Szcepanski T. Pain management in children. Ann Agric Environ Med 2013;special issue 1:28-34

16. Niesters M, Overdyk F, Smiht T, Aarts L, Dahan A. Opioid-induced depression on paediateic: a review of case reports Br J Anaesth. 2012;110:175-82

17. Khetani JD, Madadi P, Sommer DD, et al. Apnea and oxygen desaturation in children treated with opioids after adenotonsillectomy for obstructive sleep apnea syndrome: a prospective pilot study. Paediatr Drugs 2012;14:411-5

18. Madadi P, Ross CJ, Heyden MR, et al. Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case study. Clin Pharmacol Ther 2009;85:31-35

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