Microsoft word - pedi symptom booklet 2014

Pediatric Pain and Symptom
Management Guidelines
Dana Farber Cancer Institute/Boston Children's Hospital Pediatric Advanced Care Team Julie Hauer, MD, Janet Duncan, PNP, Bridget Fowler Scullion, Pharm D Prepared by Julie Hauer, MD Revised 2014 Copyright  2014, Julie Hauer. All rights reserved. Reproduction in whole or in part is strictly prohibited.
Table of Contents

Guidelines for pharmacologic management of pain
Medications for Mild and Moderate pain Opioid conversion Sample opioid conversion calculation Medications for neuropathic pain neuro-irritability Management of opioid side effects General guidelines to symptom Tapering opioids, benzodiazepines, and other drugs Spasticity/Muscle Pseudo-obstruction Pain assessment nonverbal children with neurological impairment 19-20 Neuro-irritability and Neuro-pain Transdermal, Transmucosal, and Rectal options This booklet is a guide to symptom management in children and a tool for
identifying areas for self-study. Pharmacologic options for pain and other
distressing symptoms are provided. Use of medications requires adequate
knowledge of side effects and drug-drug interactions. These suggestions
cannot replace medical judgment in how the individual characteristics of a
patient influence decisions about the use of medications, including dosage.
Many of these medications involve off-label use. Non-pharmacologic
interventions are always an essential part of symptom management.
Guidelines for Pharmacological Management of Pain
Infants < 6 months of age require lower initial opioid dosing, approximately 25-50% of the opioid doses provided Utilize your institutions developmentally appropriate symptom assessment tools to determine presence and severity of pain The World Health Organization (WHO) recommends analgesic treatment in two steps according to the child's level of pain severity1 a. Chose the drug based on degree of pain (mild, moderate or severe) Step 1 – Mild Pain Non-opioid  adjuvant agent Step 2 – Moderate to Severe Pain OR Pain Uncontrolled after Step 1 Opioid  non-opioid  adjuvant agent b. Choose the least invasive route – oral and sublingual (SL) preferred when c. Choose the dose and dose interval – for persistent, chronic pain (e.g. cancer pain), an opioid should be given scheduled around the clock, typically every 4 hours for oral or continuous for IV d. Once the daily opioid requirement is determined it can be converted to a sustained release given two or three times daily with immediate release used as needed for breakthrough pain e. Provide breakthrough (rescue) doses – typically 10-15% of the 24-hour opioid requirement, available as often as every 1-2 hour prn for oral Opioid titration – increase by 30-50% for moderate pain, 50-100% for severe pain g. If more than 3-4 doses of breakthrough medication are used daily for chronic pain, increase the dose of the sustained release opioid by an amount equivalent to 50-100% of the total amount of breakthrough medication used in 24 hours Manage side effects – initiate bowel regimen when starting an opioid Consider using both non-opioids and opioids to maximize pain relief Adjuvants enhance analgesic efficacy, treat concurrent symptoms that exacerbate pain, and/or provide independent analgesic activity for specific types of pain. Examples include anti-depressants such as amitriptyline and nortriptyline (neuropathic pain), anticonvulsants such as gabapentin and pregabalin (neuropathic pain), steroids (hepatic distention, bowel wall edema, cerebral edema), bisphosphonates (bone pain due to metastases), and radiation therapy (bone pain due to metastases). Use of combination products (e.g. acetaminophen with oxycodone) is NOT recommended. An increase in the dose can result in liver toxicity due to an increase in the acetaminophen dose. Codeine is NOT recommended as up to 1/3 of children gain no analgesic effect due to inability to convert to the active metabolite morphine and can result in toxicity in others who are ultrarapid-metabolizers. There is no "absolute" ceiling for opioids. Titrate to symptom control or to intolerable side effects. Consider opioid rotation (changing from one opioid to another) when side effects become intolerable. 10. Inadequate pain management more commonly requires dose escalation, not opioid 11. The safest opioids in renal impairment: fentanyl and methadone 12. Consider using Naloxone only if conservative measures, such as tactile stimulation, show no effect. See page 6 for dose. 13. Factors that can aggravate pain must be considered: poorly controlled pain, other symptoms (insomnia, nausea), psychosocial (depression, anxiety, family stress), cultural, spiritual 14. Non-pharmacologic interventions should be integrated into pain management (cuddling, massage, heat, cold, warm baths, physical and occupational therapy, guided imagery, meditation, hypnosis, distraction, Reiki, story telling, music and art therapy, aromatherapy, weighted blankets and vibratory stimulation in children with neurological impairment)
PO=per oral, SL=sublingual, PR=per rectum, IV=intravenous, Subcut=subcutaneous
SSRI=Selective serotonin reuptake inhibitor; SNRI=Serotonin-norepinephrine reuptake inhibitor, 5HT=serotonin, Ach=acetylcholine, D2=dopamine, H=histamine, ICP=increased intracranial pressure, NK=neurokinin, PPI=proton pump inhibitor, TCA=Tricyclic antidepressant CBC, complete blood count; CMP, comprehensive metabolic panel (includes alkaline phosphatase; alanine aminotransferase; total bilirubin); UA, urine analysis; UCx, urine culture Non-Opioids used for Mild Pain (maximum weight 50 kg)
Initial Dose (max) Interval
Dosage forms
Acetaminophen PO 10 – 15 mg/kg Many oral dosage forms (325 – 650 mg) 160 mg/5ml liquid Supp 120 mg, 325 mg, 650 mg 15 mg/kg (650 mg) Max 75 mg/kg/day PO 6 – 10 mg/kg 40 mg/ml, 100 mg/5 ml; (400 – 600 mg) 100, 200, 400, 600 mg PO 5 – 7 mg/kg 125 mg/5 ml; 220*, 250 mg (250 – 400 mg) 0.3 – 0.5 mg/kg 15 and 30 mg/ml for injection Use up to 5 days PO 10 – 20 mg/kg PO 1 – 2 mg/kg 12-24 hrs 100, 200 mg Moderate Pain
PO 1 – 2 mg/kg 50 mg; ER 100, 200, 300 mg 1. *Dosage indicated as Naproxen base; 200 mg Naproxen base is equal to 220 mg Naproxen sodium. 2. **Tramadol has a ceiling effect. If using >8 mg/kg/day (max 400 mg total daily), change to an opioid for severe pain. Use with opioids controversial. Caution: patients with seizures, on drugs that are inhibitors of cytochrome P450 2D6 isoenzyme or drugs associated with serotonin syndrome (see table on page 25)
Opioid Conversion (reduce calculated equivalent dose by 25-50%)***
Drug Equianalgesic
Hydromorphone 6-8 Oxycodone 15-20 N/A Fentanyl N/A 0.1 Opioids for Severe Pain in children > 6 months
(maximum weight for dosing is 50 kg)
Initial Dose
(dosage forms)
(initial maximum)
10 mg/5 ml, 20 mg/5 ml, SR 15, 30, 60 mg 20 mCg/kg/hr (1 mg) and 20 mCg/kg/hr PCA bolus (4-6/hr) lockout interval 5-10 min Fentanyl
Transdermal patch 12, 25, 50, 75, 100 mCg/hr; Transmucosal options Methadone
4 hr first 2-3 doses, 5 mg/5 ml, 10 mg/5 ml, 4 hr first 2-3 doses, Oxycodone
5 mg/5 ml, 20 mg/1 ml; 5, 15, 30 mg; SR 10, 20, 40, 60 mg 1. Fentanyl 25 mCg/hr patch approximately 50 mg/day oral morphine (see page 24)
2. Methadone requires expertise. PO to IV ratio is 2:1. Biphasic elimination may result
in drug toxicity 2-5 days after starting or increasing methadone 3. Opioid conversion: reduce calculated dose of new opioid by 25-50% (25%-mild
pain, 50%-no pain) due to incomplete cross-tolerance (e.g. differences in structure of opioids and affinity for various mµ receptors)
Opioid induced depressed respiratory rate
low dose: dilute 0.4mg (1 ml) of naloxone in 9 ml of saline to yield 0.04 mg
per ml, give 1-5 mCg/kg (maximum 0.04-0.2 mg) IV at 2-3 minute intervals until
response, titrate to effect, half-life is less than most opioid agonists, be prepared for the
need to re-administer naloxone boluses or use an infusion (0.5-2 mCg/kg/hour)
Sample opioid conversion calculation: A patient is on sustained release (SR)
oxycodone 10 mg po Q 8 hour and 5 mg po Q 3-4 hour break through pain. Pain is well
controlled, averaging one rescue dose of oxycodone each day. The care plan requires
conversion to intravenous. You plan to initiate a continuous IV infusion of morphine.
1. Total daily dose of scheduled SR oxycodone: 10 mg x 3 = 30 mg
Total daily dose of short acting oxycodone: 5 mg x 1 = 5 mg 30 mg + 5 mg = 35 mg oxycodone/day 2. Convert to daily morphine 20 mg of oral oxycodone = 10 mg of IV morphine 20 mg oral oxycodone 10 mg IV morphine X mg IV morphine
X = 17.5 IV morphine/day
3. Reduce the dose by 25-50% for cross-tolerance = 9-13 mg IV morphine/day; then convert to hourly rate of 0.5 mg IV morphine/hour (12 mg IV morphine/day) Opioid conversion to methadone2 (requires expertise)
Equianalgesic Conversion to Methadone IV methadone is twice as potent as oral methadone 1. Due to incomplete cross-tolerance the initial calculated methadone dose should be reduced by 25-50% and then divided into 3 doses given Q 8 hrs 2. Consider baseline EKG based on risk of prolonged QTc, such as when combined with other medications, and goals of care 3. Potential drug interactions (partial list of drugs): a. Decrease effect of methadone (or increase effect when discontinued): phenobarbital, phenytoin, carbamazepine, rifampin, St John's wort b. Increase effect of methadone: ciprofloxacin, erythromycin, fluconazole, diazepam, SSRIs, venlafaxine, verapamil, aprepitant, sodium bicarbonate, grapefruit c. Increase risk of QTc prolongation: TCA, neuroleptics, levofloxacin Neuropathic pain and Neuro-irritability* (Maximum weight 50 kg)
Thought to inhibit excitation by binding to the alpha-2-delta subunit of voltage dependent calcium ion channels in the CNS Gabapentin3 (250 mg/5 ml; 100, 300, 400 mg)
Day 1-3
2 mg/kg (100 mg) PO TID OR 5 mg/kg/dose (250 mg max) PO qhs
4 mg/kg TID OR 2.5 mg/kg/dose am and midday and 5 mg/kg qhs
6 mg/kg TID OR 2.5 mg/kg/dose am and midday and 10 mg/kg qhs
8 mg/kg TID OR 5 mg/kg/dose am and midday and 10 mg/kg qhs
Increase every 2-4 days by 5-6 mg/kg/day until 1. Effective analgesia reached (often noted at 30-45 mg/kg/day) 2. Side effects experienced (nystagmus, sedation, tremor, ataxia, swelling) 3. Maximum total dose of 50-72 mg/kg/day reached (2400-3600 mg/day) 4. Younger children (<5 years) may require a 30% higher mg/kg/day dosing, such as a total dose of 40-60 mg/kg/day4, 5 5. Half of the total daily dose may be given as the evening dose if symptoms occur mostly in the evening and overnight 6. Titrate more rapidly for severe pain or as tolerated Pregabalin (20 mg/1 ml; 25, 50, 75, 100, 150, 200, 300 mg)
1 mg/kg/dose (50 mg maximum) PO qhs 1 mg/kg/dose PO q 12 hour Increase every 2-4 days to 3 mg/kg/dose PO q 12 hour (maximum 6 mg/kg/dose) Tricyclic Antidepressants (TCA)
Presynaptic reuptake inhibition in the CNS of norepinephrine and serotonin Amitriptyline (10, 25, 50, 75 mg) or Nortriptyline3 (10 mg/5 ml; 10, 25, 50, 75 mg)
0.2 mg/kg (maximum 10 mg) PO qhs 0.4 mg/kg PO qhs Increase every 4-5 days by 0.2 mg/kg/day until 1. Effective analgesia or dosing reaches 1 mg/kg/day (maximum 50 mg/day) 2. Obtain plasma level and ECG before further dose escalation; higher rate of side effects with higher doses including anti-cholinergic; consider twice daily dosing of 25-30% in the am and 70-75% in the evening *Neuro-irritability: refers to neurologically impaired children with persistent pain behaviors, irritability, and agitation. See page 21 for suggested neuro-pain ladder and page 22 for further suggestions. Other medications used for neuropathic pain:
Serotonin norepinephrine reuptake inhibitors: duloxetine, venlafaxine
Anticonvulsants: valproic acid, carbamazepine, lamotrigine, topiramate
Cannabinoids: dronabinol (studied in central pain from multiple sclerosis)
Other adjuvants used for pain management
Apply to intact skin over most painful area, may leave in place for up to 12-hours in a 24-hour period, OK to cut 0.05-0.1 mg/kg/hr IV continuous 0.25-0.5 mg/kg PO q 6-8 hours 0.2-1 mCg/kg/hr IV adrenergic agonists 0.002 mg/kg PO qhs (0.1 mg) 0.002 mg/kg q 12 hours 0.002 mg/kg q 8 hours In addition:  Doses may be increased by 0.002 mg/kg as tolerated (monitor for hypotension), average dose for spasticity in one study 0.02 mg/kg/day (range 0.0014-0.15 mg/kg/day)  Titrate more rapidly as tolerated Corticosteroids Dexamethasone  Used for: increased intracranial pressure (ICP), cerebral edema, spinal cord compression, bowel obstruction, bowel wall edema, hepatic distention  1-2 mg/kg (maximum 50-100 mg) IV load then 0.1 mg/kg (max 4 mg) IV q 6 hrs  Higher maintenance doses for spinal cord compression associated with higher incidence of side effects without greater benefit9 0.5-1 mg/kg (max 40 mg) PO q 12 h Benzodiazepine Clonazepam 0.005-0.01 mg/kg PO q 8-12 h (initial maximum 0.25-0.5 mg) Management of Opioid Side Effects
General Approach For All Side Effects
Monitoring over several days for improvement of mild symptoms, such as
sedation and nausea, without any changes in dosing  Management of the side effect (see below)
Dose reduction of the opioid (preferably ONLY if good pain control)
Opioid rotation (switching to an alternate opioid)
Respiratory depression
 Breathing often less labored with pain control and significant opioid-induced
respiratory depression is unlikely with appropriate dosing  Risk factors: over-medication, opioid naïve patient, renal impairment, other causes of CNS depression including other medications, patients with mild pain or whose pain has been acutely relieved by a procedure Sedation and hyper-somnolence that persists (tolerance typically develops)
 Withhold less necessary drugs that are CNS depressants
 Give methylphenidate for persistent fatigue Constipation
 Laxatives are required with opioid use
 Start with a stimulant (senna)  stool softener (docusate)
 Consider adding miralax or lactulose  For refractory constipation on multiple laxatives: Naloxone 0.25-2 mCg/kg/hr10, 11 Methylnaltrexone 0.15 mg/kg (max 8-12 mg) q 48 hours subcut12 Urinary retention
 Consider bethanechol (0.2 mg/kg, max 10 mg, PO q 8 hr); bladder cathing
Nausea and vomiting
 Usually improves after several days
 Antiemetic, either scheduled or PRN (5HT3 or D2 receptor antagonists)
 Ondansetron 0.15 mg/kg PO/IV (4-8 mg) q 8 h prn
 Nalbuphine 0.01-0.02 mg/kg (1.5 mg) IV q 6 h prn itching  Opioid antagonists: naloxone (0.25-2 mCg/kg/hour, titrate to effect), naltrexone  Antihistamines not effective (opioid induced itching not histamine mediated)
 Clonazepam, Baclofen
 Assess for coexisting factors (drugs: anticholinergics; metabolic alterations:
infection, dehydration, renal, liver, electrolyte, brain metastases)  Consider use of a neuroleptic (haloperidol, risperidone, olanzapine, see page 13) Hyperalgesia
 Consider adjuvants (page 9) for pain to allow potential opioid reduction
General approach to symptom management and medication use14
 Assess for presence of symptom causing discomfort and distress  Assess the severity as well as the frequency and duration of episodes  Evaluate for causes and treat when possible (and if consistent with goals of care)  Utilize available symptom management interventions, including non-pharmacologic  Review current medications so as to minimize drug-drug interactions (see page 25) and minimize using several drugs with the same mechanism of action (increases risk of side effects from that mechanism of action)  Determine initial dose, factoring in prior response to sedating medications and the priority of goals (minimize sedation or maximize symptom improvement)  Determine minimum dose for drugs that require titration to ensure an adequate trial  Identify the timeline in which improvement is expected o Depends on onset of action and need to titrate medication over time proton pump inhibitor (PPI) gabapentin, tricyclic antidepressant, clonidine o Depends on frequency of symptoms  Shorter trial for daily symptoms, longer for intermittent  Assess for improvement using tools (when available) and parental reporting o Have the features indicating the symptom improved? (examples: moaning, facial grimacing, spasms, arching, stiffening indicating pain in a nonverbal child with impairment of the CNS; retching, flushing, sweating with autonomic dysfunction) o Has the severity of the symptom improved? o Has the frequency and duration of distressing events decreased? o How much improvement does the parent estimate: is your child 25% improved, 50% improved, greater than 50% improved?  If there is limited to no benefit in the time interval, determine if the drug will be discontinued before initiating other interventions; some drug combinations with different mechanisms of action may have benefit when there is partial benefit from the initial drug, such as the combination of gabapentin and nortriptyline15  If a drug is discontinued, drugs to taper off after prolonged use include: opioids, benzodiazepines, baclofen, gabapentin, TCA, clonidine, SSRI, SNRI
Discontinuation of opioids, benzodiazepines, and other drugs (limited studies)
General guidelines: baclofen, clonidine, and gabapentin, taper off over 2-4 weeks
(decrease by 10-20% of the original dose every 2-3 days); benzodiazepines, opioids, TCA, and SNRI, typically require longer tapering, often over 4-12 weeks  Patients on a long term oral benzodiazepine require a slow taper over 6-12 weeks, such as a decrease by an amount that is 10% of the original dose every 7 days, though in some a taper up to 6 months in duration may be needed16  Study of patients in hospital on continuous opioid or benzodiazepine: guidelines for 1–3 days duration, decrease original dose by 20% each day; 4–7 days, decrease by 13%–20% daily; 8–14 days (8%–13%); 15–21 days (3-8%); > 21 days (3%)17  In general: 1) monitor for withdrawal symptoms and adjust the wean schedule as needed, 2) consider other sources if symptoms identified during taper, 3) potential for more harm from tapering too quickly than from tapering too slowly Medications for Symptom Management (maximum weight 50 kg)
Usual Starting Dose
Dosage forms
(maximum initial dose)
Neurological problems
Spasticity/Muscle Spasms
2.5-5 mg PO q 8 hr, increase every 3 days by 5-15 mg/day to maximum of 60-80 mg/day; mg/1 ml; 10, 20 mg average dose in study: 1.9 mg/kg/day (range 0.14-9.9 mg/kg/day)18 0.002 mg/kg PO qhs (0.1 mg) 0.002 mg/kg q 12 hours mg/ml; 0.1, 0.2 mg; 0.002 mg/kg q 8 hours 0.1, 0.2, 0.3 mg/day transdermal patch 1. Titrate more rapidly if tolerated 2. Average dose in study: 0.02 mg/kg/day18 0.04-0.08 mg/kg PO qhs (2-4 mg), increase up 2, 4 mg to 0.16 mg/kg q 8 hr (max 8-12 mg q 8 hr) (Not well studied in children) 0.03-0.05 mg/kg PO/IV q 6-8 hr (2 mg), titrate 5 mg/5 ml, 5 mg/ml; to effect, maximum dose 10 mg (Short term use recommended for spasticity19 consider intermittent use for muscle spasms) Myoclonus
0.005-0.01 mg/kg PO q 8-12 hr (0.25-0.5 mg) Increase every 3 days up to 0.05-0.1 mg/kg mg/ml; 0.5, 1 mg; PO q 8-12 hr (max 0.2 mg/kg/day) oral dissolving tablet 0.125, 0.25, 0.5 mg Seizures – break through meds for seizure > 3-5 minutes or seizure cluster
0.1 mg/kg PO/buccal/PR, may repeat in 15 minutes x 2 (max dose 4 mg) buccal/intranasal (10 mg) 2-5 years 0.5 mg/kg Q 15 minutes x 3 doses Round dose to 2.5, 0.3 mg/kg Q 15 minutes x 3 doses 5, 7.5, 10, 12.5, 15, 0.2 mg/kg Q 15 minutes x 3 doses 17.5 or 20 mg/dose Anti-epileptic drugs (AEDs) that can be given rectally, if needed:
carbamazepine, phenobarbital, lamotrigine, and valproic acid (see page 24) Dysautonomia (features: agitation, flushing, sweating, tachycardia, retching)
Day 1-3 0.002 mg/kg PO qhs (0.1 mg) Day 4-6 0.002 mg/kg q 12 hours mg/ml; 0.1, 0.2 mg; Day 7-9 0.002 mg/kg q 8 hours 0.1, 0.2, 0.3 mg/day transdermal patch 1. 0.002-0.004 mg/kg q 4 hour prn "autonomic storm" 2. Average dose for spasticity in one study: 0.02 mg/kg/day (0.0014-0.15 mg/kg/day)18 3. Titrate more rapidly if tolerated Neuropathic pain section 0.2-0.3 mg/kg PO/SL q 3-4 hr prn "autonomic See page 6 Cyproheptadine 0.08 mg/kg PO q 8 hour (4 mg) If no benefit in 5 days, increase each dose by 4 mg 0.04-0.08 mg/kg, up to 0.16 mg/kg TID 0.2-0.4 mg/kg PO q 8 hr (20 mg), increase 20 & 40 mg/5 ml; every 3 days up to 1.6 mg/kg q 8 hr (80 mg) 10, 20, 40, 60 mg 0.02-0.05 mg/kg PO/SL/IV/subcut q 6 h prn See myoclonus, page 12 0.01-0.02 mg/kg PO q 8 h prn (0.5-1 mg) For acute agitation: 0.025-0.05 mg/kg PO, may repeat 0.025 mg/kg in one hour prn 0.25-0.5 mg PO in the pm or divided, titrate every 1-2 days, maximum 3 mg total/day 0.25, 0.5, and 1 mg 1.25-2.5 PO daily, increase weekly if needed, 2.5, 5, 7.5, 10, 15, up to 5 mg daily 20 mg (ODT not available in 2.5 or 7.5) 25 mg BID, increase daily by 25 mg/dose, 25, 50, 100, 200 maximum 100-200 mg BID mg; ER 50, 150 mg *Difficult to distinguish anxiety, agitation (unpleasant state of arousal), and delirium
(fluctuating disturbance of consciousness with acute onset over hours to days).
Consider sources with similar features: pain, impaired sleep, depression, metabolic
disturbances, medication reactions, and progression of a neurodegenerative condition.
Children with neurological impairment (NI) of the CNS can have a number of problems
that result in agitation and irritability (neuropathic pain, visceral hyperalgesia,
dysautonomia, muscle spasms). See pages 21-22 for symptom treatment guidelines
and suggestions in children with NI.
2-3 mg PO qhs, may increase to 12 mg receptor agonist) Trazodone 0.75-1 PO qhs (25-50 mg), increase every 1-2 weeks up to 150 mg 0.002 mg/kg PO qhs (0.1 mg), increase by 0.002 mg/kg PO qhs if needed, maximum 0.008 mg/kg qhs (0.4 mg) 0.05-0.1 mg/kg q am and q noon 5 mg/5 ml, 10 mg/5 ml; > 6 years of age: 100 mg/day weeks 1-2 100, 200 mg then 200 mg/day weeks 3-4 Depression
5-10 mg PO q day, increase every 2 10 mg/5 ml; 10, 20 mg weeks up to maximum of 40 mg q day 12.5-25 mg q day, increase weekly up to 100-200 mg daily 20-40 mg PO q day, increase weekly up 20, 30, 60 mg (do not to 60 mg q day, maximum 60 mg BID crush, capsules are extended release) 15 mg PO q day, increase weekly up to 15, 30, 45 mg (available antidepressant – as dissolving tablet) Mirtazapine (Remeron) SSRI = Selective serotonin reuptake inhibitor; SNRI = Serotonin-norepinephrine reuptake inhibitor; Tetracyclic antidepressant may also improve sleep, anxiety, nausea and vomiting (multiple receptor properties) *Consider and treat causes of sleep disruption, such as pain, dyspnea, obstructive apnea, depression, and anxiety. Gastrointestinal symptoms
Constipation (see also management of opioid side effects page 10)
0.7-1.5 gm/kg qd (8.5 – 17 g qd) 2.5 – 3.75 ml q day 8.8 mg/5 ml; 8.6 mg tablet 1/2 tablet q day (also available in combination with docusate) 0.5-1 mg/kg PO 1-4 times per day 50 mg/5 ml; 50, 100 mg Milk of Magnesia 15-30 ml PO daily or bid, give scheduled or as needed 1 suppository PR every day as 1 PR every other day as needed Fleet® enema for children Intestinal Motility
Erythromycin 2-5 mg/kg PO 4 times daily (maximum 250 mg per dose) Bowel Obstruction
0.001-0.002 mg/kg (1-2 mCg/kg) 0.003-0.006 mg/kg/day (3-6 mCg/kg/day) continuous Acute Colonic Pseudo-obstruction
Neostigmine20-22 IV 0.01-0.02 mg/kg (max 0.5-1 mg) Injection 0.5 mg/ml, 1 with monitoring (risk for bradycardia, mg/ml; hypotension, increased airway secretions and bronchial reactivity), (0.5 mg IV  15 mg PO) titrate up to 0.08 mg/kg/dose if needed20, 21 OR Subcut 0.5 mg (0.25 to 1.25 mg)22 Anorexia/Weight Loss
0.05-0.1 mg/kg PO q 12 h (2.5-5 mg) May increase if tolerated to maximum Megestrol acetate Use in children > 10 years, 100 mg PO bid, If no effect in 2 weeks, double dose to 200 mg bid (max 400 mg bid) 0.08 mg/kg PO TID (4 mg) If no benefit in 5 days, increase each dose by 0.04-0.08 mg/kg Nausea/Vomiting/Retching (receptor blocking properties indicated)
0.15 mg/kg PO/IV q 8 h prn Prokinetic: 0.1-0.2 mg/kg PO/IV q 6 h 5 mg/5 ml; D2 – prokinetic 0.01-0.02 mg/kg PO q 8 h prn See Anxiety/Agitation/Delirium on D2, 5HT2, 5HT3, H1 page 13 1 mg/kg PO/IV q 6 h prn 12.5 mg/5 ml; 25, 50 mg Adolescents: 1.5 mg by transdermal Adolescents: 125 mg PO 1 hour prior 40, 80, 125 mg to chemo, then 80 mg q day on days 2 & 3 0.02-0.05 mg/kg PO/SL/IV/SQ q 6 h 0.1 mg/kg PO/IV q 6 h (maximum 16 See above – may benefit neurologically impaired children with retching and feeding intolerance Sources of Nausea and Vomiting
Central Sites
Therapeutic Agents
(Diphenhydramine) Anticholinergics 5HT2 antagonists (Cyproheptadine) Serotonin antagonists (chemo, opioids, (Ondansetron, Granisetron) anticonvulsants) (Haloperidol, Droperidol) Atypical antipsychotic acidosis, uremia) Toxins (ischemic Disorders of the vestibular nucleus (H1) (Diphenhydramine) and cranial nerve Anticholinergics Stimulation of Corticosteroids Mechanoreceptors tumor, infection Relaxation Techniques, Gastrointestinal Sites
Mechanoreceptors Drugs, (opioids, H2-Blockers, PPI anticholinergics), (Ranitidine, Omeprazole); Prokinetic Agents (Metoclopramide) (Diphenhydramine) gastritis, chemo, radiation, tumor, Serotonin antagonists hepatic distention (Ondansetron, Granisetron) Abbreviations: 5HT=serotonin, Ach=acetylcholine, D2=dopamine, H=histamine, ICP=increased intracranial pressure, NK=neurokinin, PPI=proton pump inhibitor Respiratory Symptoms
0.05-0.1 mg/kg PO or 0.015-0.03 mg/kg IV/subcut q 3-4 h prn (5 mg PO, 2.5 mg IV) (or other opioids at equivalent dose) 0.02-0.05 mg/kg PO/SL/IV/subcut q 6 h prn 0.1-0.2 mg/kg PO/SL (5-10 mg) 2 Respiratory Secretions (use cautiously for chronic secretion management)
250-500 mCg nebulization Q 4-6 h prn Glycopyrrolate 0.04-0.05 mg/kg PO q 4-8 h (1-2 mg) 0.004-0.005 mg/kg (4-10 mCg/kg) IV q 3-4 h 1% ophthalmic drops Scopalomine Adolescents: mg transdermal patch q 72 h 0.125 mg/1 ml solution 4 drops PO q 4 hours prn 8 drops PO q 4 hours prn 1 ml (0.125 mg) PO q 4 hours prn 0.125 mg/5 ml elixir 1.25 ml PO q 4 hours prn 2.5 ml PO q 4 hours prn 3.75 ml PO q 4 hours prn 5 ml (0.125 mg) PO q 4 hours prn Pain assessment in non-verbal children with neurological impairment (NI)24  Behaviors associated with pain in this population include (examples noted with Revised-FLACC): vocalizations (crying, moaning), facial expression (grimacing), consolability, interactivity (withdrawn), diminished sleep, movement (restless, increased movement of extremities), tone and posture (arching, stiffening), and physiological responses (diaphoresis, pallor, tachycardia)  Core pain behaviors are consistently identified in this population yet each child will display a unique set of behaviors  Unique behaviors can range from crying in one child to withdrawn in another and include idiosyncratic behaviors in some such as laughing, clapping, and blunted facial expression  This unique and variable expression necessitates input from a consistent care provider, often a parent, with knowledge of a child's typical behavior patterns at baseline and in response to painful and non-painful (such as hunger) stimulus  It is important to be vigilant to the possibility of pain in children with NI. There is often a focus on management of such problems as spasticity, autonomic dysfunction, or feeding intolerance without considering pain as a coexisting and exacerbating source of these problems (see pages 21-22)  Advantages of revised-FLACC25 and Individualized Numeric Rating Scale (INRS)26: ease of use and ability to individualize by adding behaviors specific to a child  Other tools available include the Paediatric Pain Profile27 (PPP), available to download at following registration  See examples of pain behaviors in revised-FLACC Individualized behaviors* Consistent grimace Examples: ‘Pouty' lip; clenched and grinding Frequent/constant furrowed; stressed looking; stern face; appears sad or Distressed looking eyes wide open, looks face; Expression of surprised; blank fright or panic; Other (write-in) Kicking, or legs Legs and arms drawn restless, tense; drawn up; marked to center of body; clonus in left leg with spasticity, constant pain; very tense and tremors or jerking still; legs tremble Other (write-in) Arched, rigid or Grabs at site of pain; nods head; clenches fists, draws up arms; banging; shivering arches neck; arms (not rigors); breath startle; turns side to holding, gasping or side; head shaking; points to where it hurts; clenches fist to face, hits self, forth); splinting Other (write-in) slapping; tense, guarded, posturing; thrashes arms; bites palm of hand; holds Crying steadily, States, ‘I'm okay' or screams or sobs, ‘All done'; mouth wide open; states ‘Owie' or ‘No'; gasping, repeated outbursts, screaming; grunts or verbal outburst constant grunting short responses; Other (write-in) whining, whimpering, shouting; crying is rare Consolability Content and Reassured by Difficult to console Responds to cuddling, or comfort; pushing holding, parent, stroking, kissing; resisting care or being talked to; comfort measures unresponsive when in Other (write-in) *Examples of additional pain behaviors identified by parents25 Guideines: 1. Review with parent/caregivers to identify behaviors and features that can indicate pain 2. Indicate behaviors on the R-FLACC, adding those not listed 3. Use to indicate to others the child's pain behaviors and to document pain score as needed
Individualized Numeric Rating Scale (INRS): In the diagram below, write in your child's
typical pain behaviors on the line that corresponds to its pain intensity, where 0 = no pain and
10 = worst possible pain (see article for further information)26


Pc131086 1.20

This article is a Plant Cell Advance Online Publication. The date of its first appearance online is the official date of publication. The article has beenedited and the authors have corrected proofs, but minor changes could be made before the final version is published. Posting this version onlinereduces the time to publication by several weeks. A Secreted Effector Protein of Ustilago maydis Guides MaizeLeaf Cells to Form Tumors

MINIMALLY INVASIVE ANTRAL MEMBRANE BALLOON ELEVATION • MAZOR ET AL Flapless Approach to Maxillary Sinus Augmentation Using Minimally Invasive Antral Membrane Balloon Elevation Ziv Mazor, DMD,* Efraim Kfir, DMD,† Adi Lorean, DMD,‡ Eitan Mijiritsky, DMD,§ and Robert A. Horowitz, DDS储 Posteriormaxillaryimplantplace- In the atrophic posterior max- floor. The surgical procedure was

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