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Palliative Care For Children General Overview Professor, Faculty of Medicine, University of Manitoba Medical Director, Winnipeg Regional Health Authority.

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Presentation on theme: "Palliative Care For Children General Overview Professor, Faculty of Medicine, University of Manitoba Medical Director, Winnipeg Regional Health Authority."— Presentation transcript:

1 Palliative Care For Children General Overview Professor, Faculty of Medicine, University of Manitoba Medical Director, Winnipeg Regional Health Authority Palliative Care Program Co-Chair, Canadian Network of Palliative Care for Children Physician Consultant, Canadian Virtual Hospice Mike Harlos MD, CCFP, FCFP

2 Objectives To consider the definition of pediatric palliative care To consider where pediatric palliative care may fit in the care of seriously ill children To consider similarities/differences with palliative care for adults To review the prevalence and management of symptoms in children living with life-threatening illness

3 Prognostic Uncertainty Pediatric Palliative Care services providers must acknowledge the uncertainty involved in determining if a specific circumstance or condition is life-limiting / life-threatening

4 Common Trajectory Of Decline In Progressive Life-Limiting Illness In Children Functional Status Time Decline Crises (Scary Dips) Death From presentation by Joanne Wolfe at the 16 th International Congress on the Care of The Terminally Ill

5 Prognostic Irrelevance In the view of patient, family, and/or care team, there may be unwillingness to even consider the possibility of death Service availability should not only accommodate prognostic uncertainty, but should not require acceptance of a threatened life

6 What if…? What would things look like? Time frame? Where care might take place What should the patient/family expect (perhaps demand?) regarding care? How might the palliative care team help patient, family, health care team? What would things look like? Time frame? Where care might take place What should the patient/family expect (perhaps demand?) regarding care? How might the palliative care team help patient, family, health care team? Palliative Care… The What If…? Tour Guides Disease-focused Care (Aggressive Care) Disease-focused Care (Aggressive Care)

7 Addressing The What-Ifs… Silence Is Not Golden Children (even young children) are very perceptive, and can tell when something serious is happening Even when pursuing cure for their child, parents are often aware in their heart of hearts that things may not unfold as hoped for Palliative Care has a role in: –helping families navigate through difficult decisions, at times conflicted about which course is best for their child… path of least regret –ensuring that comfort and quality of life are minimally affected by the impact of illness, tests, and treatments –facilitating communication about fears and worries, and open dialogue about what to expect

8 Kreicbergs et al NEJM 2004; 351(12): Did you talk about death with your child at any time? Talking about Death with Children … ctd Yes n = 147 (34 %) No n = 282 (66 %) Do you regret having done so? Do you regret not having done so? No parents regretted having talked with their children about dying YesNo Overall: Sensed Child Aware Of Dying: Did Not Sense Child Aware: 27% 47%53% 87% 13% 73% Identify and facilitate communication

9 What Symptoms Do Children With Advanced Illness Experience?

10 The Measurement Of Symptoms In Children With Cancer Collins JJ, Byrnes ME, Dunkel IJ, Lapin J, Nadel T, Thaler HT et al. J Pain Symptom Manage 2000; 19(5): n = 160 cancer patients receiving treatment aged 10 – 18 yo 30-item patient-rated instrument (MSAS 10-18) Inpatients averaged 13 symptoms, outpatients 6.5 Patients who had recently received chemotherapy had more than double the symptoms of those who had not

11 Symptoms At The End of Life in Children With Cancer Wolfe J. et al, NEJM 2000; 342(5) p % Pain Dyspnea Nausea And Vomiting Successfully Treated (% Of Affected Children) 27 % 16 % 10 %

12 Pain In Advanced Childhood Illness Abstract from the 7 th International Symposium on Pediatric Pain Stenekes S, Hughes A, Grégoire MC, Frager G 2006 Symptom Prevalence At Study Entry And In Last Month Of Life UK Childrens Cancer Study Group/Paediatric Oncol Nurses Forum Survey Goldman A et al; Pediatrics 2006; 117; Engel JM, Jensen MP, Hoffman AJ, Kartin D. Pain in persons with cerebral palsy: extension and cross validation Arch Phys Med Rehabil 2003; 84(8): Breau LM, Camfield CS, McGrath PJ, Finley GA. The incidence of pain in children with severe cognitive impairments. Arch Pediatr Adolesc Med 2003; 157(12):

13 Hunt and Burne, 1995 Symptoms in Children with Neurodegenerative Illness %

14 2002 College Of Physicians And Surgeons Of Manitoba Child Health Standards Committee Report 2002 Manitoba Deaths Unlikely role for Palliative Care in symptom management, though potentially in family and staff support Potential role for Palliative Care in symptom management as well as family and staff support

15 Palliative in Parallel Palliative care for children should not be exclusive of ongoing cure-focused care Can be involved as a parallel process, with a variable profile depending on goals of care and clinical circumstances It is not unusual for children/families/clinicians to harbour seemingly conflicting thoughts and contradictory goals There are some situations where one could argue that the standard of care should require involvement of a palliative service… eg: –Phase One Clinical trials –Organ Transplant waiting lists

16 Cure-Oriented; Disease-Focused Palliative Various Patterns Of Pediatric Palliative Care Involvement

17 Patient Groups For Pediatric Palliative Care Services Comfort-focused approach has been chosen, or disease-focused interventions not possible Group 1A Advanced life-limiting condition from which death within 12 months would not be unexpected Group 1 Children with progressive life- limiting/life-threatening conditions who are not expected to survive into adulthood, but whose prognosis is anticipated to exceed one year Group 2 Advanced life-limiting illness with substantial disease and symptom burden for whom cure is nonetheless hoped for, or for whom all aggressive disease-focused and potentially life- sustaining options are being pursued Group 1B

18 Medical expert providing anticipatory guidance, well child care Medical expert dealing with child and youth maltreatment abuse Medical expert dealing with the chronic care of complex problems Medical expert dealing with palliative care Medical expert dealing with death and bereaved parents Procedural skills Communicator - working successfully with difficult patients families Communicator - working successfully with cultural or socioeconomic differences Collaborator - working as a member of a team Manager - learning principles of quality management Manager - managing an efficient office practice Health advocate for individual patients Health advocate for disadvantaged children or child health issues Scholar - ability to carry out a research project Scholar - ability to critically appraise literature Professional and ethical issues Pediatricians Sense Of Preparedness For Practice Lieberman L, Hilliard LI; Medical Education 2006; 40: 539–546 Medical expert providing anticipatory guidance, well child care Medical expert dealing with child and youth maltreatment abuse Medical expert dealing with the chronic care of complex problems Medical expert dealing with palliative care Medical expert dealing with death and bereaved parents Procedural skills Communicator - working successfully with difficult patients families Communicator - working successfully with cultural or socioeconomic differences Collaborator - working as a member of a team Manager - learning principles of quality management Manager - managing an efficient office practice Health advocate for individual patients Health advocate for disadvantaged children or child health issues Scholar - ability to carry out a research project Scholar - ability to critically appraise literature Professional and ethical issues Medical expert providing anticipatory guidance, well child care Medical expert dealing with child and youth maltreatment abuse Medical expert dealing with the chronic care of complex problems Medical expert dealing with palliative care Medical expert dealing with death and bereaved parents Procedural skills Communicator - working successfully with difficult patients families Communicator - working successfully with cultural or socioeconomic differences Collaborator - working as a member of a team Manager - learning principles of quality management Manager - managing an efficient office practice Health advocate for individual patients Health advocate for disadvantaged children or child health issues Scholar - ability to carry out a research project Scholar - ability to critically appraise literature Professional and ethical issues Medical expert providing anticipatory guidance, well child care Medical expert dealing with child and youth maltreatment abuse Medical expert dealing with the chronic care of complex problems Medical expert dealing with palliative care Medical expert dealing with death and bereaved parents Procedural skills Communicator - working successfully with difficult patients families Communicator - working successfully with cultural or socioeconomic differences Collaborator - working as a member of a team Manager - learning principles of quality management Manager - managing an efficient office practice Health advocate for individual patients Health advocate for disadvantaged children or child health issues Scholar - ability to carry out a research project Scholar - ability to critically appraise literature Professional and ethical issues n = 239 pediatricians certified in Canadian training programs between1999 and 2003

19 Keeping The Momentum – Recent Developments 2003: Canadian Network of Palliative Care for Children (CNPCC)- see March Pediatric Hospice Palliative Care Guiding Principles And Norms Of Practice, through joint work by the CNPCC and CHPCA 2006: 1 st major clinical textbook in pediatric palliative care, The Oxford Textbook of Palliative Care for Children. 2006: The Canadian Council on Health Services Accreditation (CCHSA) released in its standards for Hospice and End-of-Life Care The Royal College of Physicians and Surgeons of Canada is exploring core competencies in Pediatric Palliative Care There is increasing interest is there amongst physicians training in Pediatrics

20 Pain Assessment In Children Pain can be measured by: –self-report (what children say) – Gold Standard –biological markers (how their bodies react) –behaviour (what children do) Biological and behavioural measures tend to habituate over time; parameters may not be specific to pain. May deny pain if the questioner is a stranger, if they believe they are supposed to be brave, if they are fearful, or if they anticipate receiving an injection for pain. Much variability in developmental capacity for children to report and describe pain Questioning should be patient & use words familiar to the child, eg. –"Do you have any hurt?" –"Is there an owie or boo-boo in your tummy?"

21 Pain Assessment Self-Reporting and Developmental Stage Children have words for pain by about 18 months if age; may prefer the word hurt rather than pain; may use idiosyncratic, family words Most children > 2 yrs can report presence & location of pain 3 – 4 yrs: cognitive skills to describe pain intensity (eg. a little, a lot) 4-5 yrs: can use the Poker Chip scale Can test ability to use pain-rating tools with simple test of seriation By about 5 yrs – capacity to provide good qualitative and quantitative information

22 Pain Assessment Self-Reporting and Developmental Stage ctd … 5+ yrs can usually rate and score pain; the Bieri Faces Pain Scale may be used –Children point to a face on the scale that matches how they feel. –The child should be trained by asking how he or she would feel following some minor pain. The child is asked about how much a more serious pain would hurt. 7+ yrs: children can rate pain on a 0 (no pain) – 10 (worst possible pain) scale 8+ yrs are able to describe the quality of the pain experience Describing how pain affects emotions requires more abstract concepts Adolescents are quite capable of using scales that use adjectives to describe both affect and sensory intensity

23 Faces Pain Scale – Revised Children Beginning At 3-4 yo Avoid affective descriptors (eg. Point to the face that shows how you are feeling) May be misinterpreted as are you happy/sad?

24 1.Pain often unrecognized and undertreated. Neonates do feel pain, and analgesia should be prescribed when indicated during their medical care. 2.If something hurts adults, it will hurt newborns, even if they are preterm. 3.Compared with older age groups, newborns may experience a greater sensitivity to pain and are more susceptible to the long-term effects of painful stimulation. 4.Adequate treatment of pain may be associated with complications and mortality. 5.The appropriate use of environmental, behavioral, and pharmacological interventions can prevent, reduce, or eliminate neonatal pain in many clinical situations. 6.Sedation does not provide pain relief and may mask the neonate's response to pain. 7.Health care professionals have the responsibility for assessment, prevention, and management of pain in neonates. 8.Clinical units providing health care to newborns should develop written guidelines and protocols for the management of neonatal pain. Anand KJ. Consensus statement for the prevention and management of pain in the newborn. Arch Pediatr Adolesc Med 2001; 155(2): General Principles For The Prevention And Management Of Pain In Newborns

25 Approach To Analgesia Use In Pediatric Palliative Care The oral (enteral) route preferred for most children, most of the time However… many alternate routes available if needed: –IV (peripheral and central) –Subcutaneous –Transmucosal (nasal, buccal, sublingual) –Transdermal / transcutaneous –Spinal (epidural, intrathecal) –Rectal (usually not well tolerated) Use adjuvants as appropriate The W.H.O. ladder is a good template on which to base analgesic use Virtually always prescribe laxatives with opioid Rx

26 Weak Opioids Used In Pediatric Palliative Care Codeine remains the most commonly prescribed weak opioid, however there are considerations: Codeine is a pro-drug of morphine, from which its analgesic effect is derived Up to 10% of the Caucasian population lack the enzyme necessary for transformation of codeine to morphine; perhaps up to 47% of those < 12 yrs old If 1 mg/kg codeine ineffective, switch to morphine or alternative Oxycodone: has some κ receptor agonist activity as well as μ No ceiling dose – can potentially be continued throughout course of illness

27 STRONG OPIOIDS Children > 3 months are probably at no greater risk of signif. resp depression than adults; younger infants may have risk due to metabolic immaturity affecting pharmacokinetics Morphine elimination t ½ (h): Preterm infants: 9 – 10 Term Infants: 7 Children: 3 – 4 (Saaranmaa E, Huttunen P, Leppaluoto J, Meretoja O, Fellman V. Advantages of fentanyl over morphine in analgesia for ventilated newborn infants after birth: A randomized trial. J Pediatrics 134[2], )

28 STRONG OPIOIDS ctd most commonly use: –morphine –hydromorphone (Dilaudid ®) –fentanyl (IV infusions) –oxycodone –methadone DO NOT use meperidine (Demerol®) long-term –active metabolite normeperidine seizures

29 Using Opioids for Breakthrough Pain Patient/Family must feel in control, empowered Use aggressive dose and interval There should be confidence in the effectiveness of the breakthrough dose; empirically and reliably effective Patient Taking Short-Acting Enteral Opioids: % of the q4h dose given q1h prn Patient Taking Long-Acting Enteral Opioids: % of total daily dose given q1h prn using short-acting opioid preparation Patient On Continuous Parenteral Infusion (non-PCA): 1 – 2 hrs worth of opioid, given q15 minutes prn

30 PCA Opioids Allows patients to self administer small amounts of opioids when needed Usually IV or SQ Most commonly morphine or hydromorphone May have a continuous background opioid infusion in addition to PCA boluses A child able to play a video game can also operate a PCA pump (5 – 6 yo) Varying policies on whether nurse or parent are allowed to initiate a bolus – doing so will lose the inherent safety of being too drowsy to self-overdose Ref: Pain In Infants, Children, And Adolescents 2 nd Ed, 2003; Schechter, Berde, and Yaster Editors

31 AgentIntermittent DoseParenteral Infusion Dose CodeineEnteral0.5 – 1.0 mg/kg q4hNot recommended parenterally Morphine Sulfate Enteral0.2 – 0.3 mg/kg q 4h 0.05 mg/kg IV load over 10 min then 0.01 – 0.03 mg/kg/hr IV/SQ0.05 – 0.2 mg/kg q 2-4h Hydromorphone Enteral30 – 80 micrograms/kg q4h 10 – 20 micrograms/kg IV load over 10 min then 2 – 8 micrograms/kg/hr IV/SQ15 micrograms/kg q 2 – 4h Oxycodone0.05 – 0.15 mg/kg po q4hN/A Fentanyl Citrate0.5 – 2 micrograms/kg IV0.5 – 2 micrograms/kg/hr IV Recommended Opioid Analgesic Doses (> 6 Months Age)* * For infants < 6 months start with ¼ of the pediatric starting dose and titrate

32 Opioid Side Effects Constipation – need proactive laxative use Nausea/vomiting – consider treating with dopamine antagonists and/or prokinetics (metoclopramide, domperidone, prochlorperazine [Stemetil], haloperidol) Urinary retention Itch/rash – worse in children; may need low-dose naloxone infusion. May try antihistamines, however not great success Dry mouth Respiratory depression – uncommon when titrated in response to symptom Drug interactions Neurotoxicity (OIN): delirium, myoclonus seizures

33 Opioid-Induced Pruritus Not rare; up to 23% in children > 12 yo in one study of long- acting morphine ( Zernickow B, Lindena G; Medical and Pediatric Oncology 36:451±458 (2001) ) Pathophysiology unclear –opioid receptors are relevant to the modulation of pain and itch in the central nervous system. –Opioid peptides may also have a peripheral action potentiating itch due to other agents Consider switching opioids; may have less pruritus with fentanyl, methadone, oxycodone Try antihistamines (diphenhydramine, Atarax, trimeprazine) Naloxone 1 – 2 micrograms/kg/hour as an infusion

34 Adjuvants Used In Palliative Care General / Non-specific –corticosteroids Bone Pain –NSAIDs –bisphosphonates –(calcitonin) Neuropathic Pain –gabapentin –antidepressants –ketamine –topiramate –clonidine –cannabinoids (not yet commonly used for pain)

35 Gabapentin For Neuropathic Pain Common Starting Regimen: –5 mg/kg hs days 1-3, then –5 mg/kg bid days 4-6, then –5 mg/kg tid and slowly titrate up –Usual effective range: 8 – 35 mg/kg/day Sedation is usual limiting factor. Doses may need to be rounded of due to the capsule strengths

36 Intranasal Meds DrugT max (min)Bioavailability (%) Midazolam 1,2 11 – 14*55 – 83 Fentanyl Sufentanil Hydromorphone 4 20 – P. D.Knoester ; Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers ; Br J Clin Pharmacol May;53(5): Rey E. et al; Pharmacokinetics of midazolam in children: comparative study of intranasal and intravenous administration ; Eur J Clin Pharmacol 41(4) 1991; Dale O, Hjortkjaer R, Kharasch ED; Nasal administration of opioids for pain management in adults ; Acta Anaesthesiol Scand Aug;46(7): Coda BA, Rudy AC, Archer SM, Wermeling DP; Pharmacokinetics and bioavailability of single-dose intranasal hydromorphone hydrochloride in healthy volunteers ; Anesth Analg Jul;97(1): Fisgin T et al; Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study ; J Child Neurol Feb;17(2):123-6 * Available to the cerebral cortex 2 – 5 min. after nasal use 5 Reasonable to start with recommended mg/kg for IV dosing and adjust empirically

37

38 Management Of: Nausea And Vomiting Dyspnea Secretions In Pediatric Palliative Care

39 Cortex CTZ Vestibular GI VOMITING CENTRE

40 Managing Nausea & Vomiting in Palliative Care Some Differences in Children vs. Adults Assessment, communication challenges Higher risk of extrapyramidal reactions, akathisia, and somnolence with dopamine antagonists in children than adults – Metoclopramide (Maxeran®) – Prochlorperazine (Stemetil®) – Haloperidol (Haldol®) – Chlorpromazine If using dopamine antagonists, consider slow administration (45-60 min.), as well as concomitant use of diphenhydramine (Benadryl®) 0.5 – 1 mg/kg q4-6h po/IV continued for additional 24hrs after dopamine antagonist stopped.

41 StimulusAreaReceptors Drugs, Metabolic Chemoreceptor trigger zone Motion, Position Vestibular VisceralOrgans ? Non- specific CNS ICP Cerebral cortex D 2 5HT M H1H1H1H1 VOMITING CENTRE Effector Organs Dopamine SerotoninHistamine Muscarinic CB 1 Cannabinoid CB 1 D 2 D 2 5HT H1H1H1H1 H1H1H1H1 H1H1H1H1 M M

42 From: Arch. Dis. Child. 2004;89; E S Antonarakis and R D W Hain Nausea and vomiting associated with cancer chemotherapy: drug management in theory and in practice

43 Drug Class Examples for Breakthrough Nausea (Not necessarily the same as for Chemotherapy Protocols) Serotonin Antagonists Granisetron 1 : 4 yo: mcg/kg/day divided once or twice daily single dose po/IV Ondansetron 2 : 0.15 mg/kg/dose enterally/IV q 6-8h H 1 AntagonistsDimenhydrinate (Gravol®): 1.25 mg/kg q6h (max. 50 mg/dose); not recommended < 2 yo Dopamine Antagonists (Consider concomitant diphenhydramine 0.5 – 1.0 mg/kg) Prochlorperazine (Stemetil®): 0.1 – 0.15 mg/kg po/pr q6h Methotrimeprazine: 1 mo y: mg/kg continuous infusion over 24h (or mg/kg q6h) Metoclopramide: 0.1 – 0.2 mg/kg po/IV/SQ q6h prn (dont use if Hx seizures) Haloperidol: 0.01 – 0.02 mg/kg po/IV/SQ/SL/pr q 8-12h Domperidone: 1.2 – 2.4 mg/kg/day divided TID – QID (doesnt cross BBB) ProkineticsSee metoclopramide and domperidone above Cannabinoids Dronabinol: mg/m 2 q4h prn; alternatively 0.04 to 0.12 mg/kg/day (much lower dose) Nabilone: (> 4 yo): 30 kg: 1 mg tid CorticosteroidsDexamethasone: mg/kg initially then mg/kg q6h Antinauseants / Antiemetics 1 Komada Y et al. A randomised dose-comparison trial of granisetron in preventing emesis in children with leukaemia receiving emetogenic chemotherapy. Eur J Cancer 1999; 35(7): Principles and Practice of Pediatric Oncology 4th Ed.; Edited by Pizzo & Poplack

44 Palliative Management of Secretions

45 Secretions - Prevalence At Study Entry And In Last Month Of Life UK Childrens Cancer Study Group/Paediatric Oncology Nurses Forum Survey Goldman A et al; Pediatrics 2006; 117;

46 Managing Secretions in Palliative Patients Factors influencing approach management: Oral secretions vs. lower respiratory Level of alertness and expectations thereof Proximity of expected death Death Rattle – up to 50% in final hours of life At times the issue is more one of creating an environment less upsetting to visiting family/friends Suctioning: If you can see it, you can suction it Suctioning Increased Secretions Mucosal Trauma

47 Atropine Eye Drops For Palliative Management Of Secretions Atropine 1% ophthalmic preparation Local oral effect for excessive salivation/drooling Dose is usually 1 – 2 drops SL or buccal q6h prn There may be systemic absorption… watch for tachycardia, flushing

48 Glycopyrrolate For Palliative Management Of Secretions Enteral: 40 – 100 micrograms/kg 3 – 4 times daily 2006 British National Formulary For Children IWK Health Centre (Halifax) Formulary Refs: Parenteral: 4 – 10 micrograms/kg 3 – 4 times daily (10x the enteral dose) IWK Health Centre (Halifax) FormularyRef: Less sedating than scopolamine (doesnt cross the blood-brain barrier), longer acting, however not as effective Useful where patient is still alert; scopolamine will cause sedation and delirium in awake patients

49 Scopolamine For Palliative Management Of Secretions Transderm-V ® (Scopolamine) AgeDose 1 month – 3 yrs250 micrograms every 72 hours (1/4 patch) 3 – 10 yrs500 micrograms every 72 hours (1/2 patch) 10 – 18 yrs1 mg every 72 hours (one patch) Ref: 2006 British National Formulary For Children Intermittent SQ/IV: 10 micrograms/kg (max. 600 micrograms) q 4h Continuous SQ/IV: microgram/kg/day (1.67 – 2.5 microgram/kg/h) 2006 Rainbow Hospice GuidelinesRef:

50 Dyspnea In Pediatric Palliative Care

51 DYSPNEA An uncomfortable awareness of breathing Not the same as tachypnea, which is a fast rate of breathing...the most common severe symptom in the last days of life (Davis C.L. The therapeutics of dyspnoea Cancer Surveys 1994 Vol.21 p 85 – 98) Increasing incidence as death nears (approx. 80 %); pneumonia at the end of life

52 Anti-tumor: chemo/radTx, hormone, laser Infection Anemia CHF SVCO Pleural effusion Pulmonary embolism Airway obstruction TREAT THE CAUSE OF DYSPNEA - IF POSSIBLE AND APPROPRIATE

53 Opioids in Dyspnea Uncertain mechanism Comfort achieved before resp compromise; rate often unchanged Often patient already on opioids for analgesia; if dyspnea develops it will usually be the symptom that leads the need for titration Dosage should be titrated empirically; may easily reach doses commonly seen in adults May need rapid dose escalation in order to keep up with rapidly progressing distress

54 AgentIntermittent DoseParenteral Infusion Dose CodeineEnteral0.5 – 1.0 mg/kg q4hNot recommended parenterally Morphine Sulfate Enteral0.2 – 0.3 mg/kg q 4h 0.05 mg/kg IV load over 10 min then 0.01 – 0.03 mgkg/hr IV/SQ0.05 – 0.2 mg/kg q 2-4h Hydromorphone Enteral30 – 80 micrograms/kg q4h 10 – 20 micrograms/kg IV load over 10 min then 2 – 8 micrograms/kg/hr IV/SQ15 micrograms/kg q 2 – 4h Oxycodone0.05 – 0.15 mg/kg po q4hN/A Fentanyl Citrate0.5 – 2 micrograms/kg IV0.5 – 2 micrograms/kg/hr IV Lorazepam0.05 mg/kg IV/SL Midazolam IV – 0.05 mg/kg titrated carefully, with 2-3 min. between fractions Infusion would be guided by prn doses …neither surgical anesthesia nor fatal intoxication is produced by benzodiazepines in the absence of other drugs with CNS- depressant actions; an important exception is midazolam, which has been associated with decreased tidal volume and respiratory rate (Goodman & Gilman) Nasal0.1 mg/kg in each nostril po/SL Child 1 month–18 years 0.5 micrograms/kg (max. 15 mg) 30–60 minutes before procedure Methotrimeprazine mg/kg q6h po/SQ mg/kg/24 hr IV/SQ Recommended Opioid And Sedative Doses For Dyspnea (> 6 Months Age)* * For infants < 6 months start with ¼ of the pediatric starting dose and titrate


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