Trust Guideline for the Management of Painful Crisis in Children with Sickle Cell Disease
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1 Sickle Cell Disease A clinical guideline recommended for use In: By: For: Key words: Written by: Supported by: Approved by: Reported as approved to the: Accident and Emergency, Children s Assessment Unit, Buxton Ward. Nurses, SHOs, SpRs, Consultants Children < 16 years Sickle, pain, crisis, analgesia, guideline. Dr Jo Ponnampalam, Consultant Paediatrician/Haem.Onc,NNUHFT Dr Hamish Lyall,Consultant Haematologist, NNUHFT Dr J Wimperis, Consultant Haematologist, NNUHFT Dr Mike Gattens,Consultant Paediatric Haematologists, Addenbrookes Hospital Accepted by James Paget University Hospital under the Tri- Hospital Clinical Guidelines Assessment Panel (THCGAP) Chair s action 29 September 2014 and reported to Clinical Guidelines Assessment Panel (CGAP) 15 October 2014 Clinical Standards Group Effectiveness Sub-Board Date of approval September 2014 To be reviewed before: Amended August 2014 (following MHRA alert not to use codeine in children<12 years of age and restrictions to those<19 years of age) To be reviewed by: 27 August 2017 Dr J Ponnampalam, Consultant Paediatrician Guideline supersedes: CA4057 v5 Guideline Reg. No: JCG0023 v1 Copy of complete document available from: Trust Intranet Page 1 of 15
2 Sickle Cell Disease Quick reference guideline/s See page 5 and 6 of this guideline. Objective/s Pain in sickle cell disease is thought to be due to complex and poorly understood interactions between biological and psychosocial factors. This guideline aims to provide a basic minimum standard of care for patients with acute painful crisis, paying particular attention to adequate analgesia based on results of randomised controlled trials. Rationale Severe acute pain is the most common manifestation of sickle cell disease requiring hospital admission. Inappropriate treatment leads to unnecessary suffering, potentially fatal complications and repeated admissions 3. Vaso-occlusion within the bone marrow vasculature leads to bone infarction and release of inflammatory mediators that activate afferent nerve fibres causing pain. Hospital admissions for acute pain in sickle disease typically last 4-10 days, but this may vary widely 3. The guidelines are based on recommendations by British Society of Haematology published in 2003, Cochrane review of pain management in sickle cell disease in 2006, guidelines from The Royal London Hospital and North Middlesex Hospital Haemoglobinopathy service and recommendations from the recent NICE guidelines on acute sickle cell pain, June Conditions covered by this guideline Homozygous sickle cell anaemia (HbSS) accounts for 70% of patients in UK while compound heterozygote for HbS and HbC (HbSC) and HbSβthal contribute to majority of the rest. Broad recommendations Codeine preparations are no longer to be used as per MHRA alert on the use of codeine in children<18 years of age June On presentation, children with sickle cell disease should be assessed for severity of pain despite the dose and type of analgesia already administered at home. If pain is not controlled on non - opioids (Paracetamol, Ibuprofen), a stronger opioid like Morphine should be considered. Children should be assessed for complications and treated promptly and appropriately. Adequate hydration status and oxygenation (saturation>95%) play a key role in management. Oxygen saturations should be measured off oxygen on admission and maintained at >95%. Copy of complete document available from: Trust Intranet Page 2 of 15
3 Initial assessment Triage as high priority Offer analgesia for pain within 30 minutes of arrival to hospital Measure oxygen saturations in air. Maintain oxygen saturation >95% Assess for Infection Dehydration Acute chest syndrome (fever, tachypnoea, chest pain, hypoxia, chest signs), Girdle syndrome (abdominal pain due to vaso occlusion, gut ischaemia) Cholecystitis Splenic enlargement Neurological events Priapism Pain Management Offer analgesia within 30 minutes of presentation to hospital with acute painful crisis 4 (ensure detailed pain history and whether caused by painful crisis or whether alternative diagnosis should be considered especially if pain reported as atypical by patient) Accurate analgesic history: Usual analgesia taken, dose, timing and effectiveness. Assess severity of pain (See pain assessment tool appendix-1 as well as parental assessment). Aim for relief of pain according to WHO pain relief ladder 5 (Page 4). If severe pain: reassessment hourly for the first 3 hours (Flow chart - page 5). Ensure adequate hydration especially with NSAIDs. Consider non drug methods in pain management such as distraction play therapy. Copy of complete document available from: Trust Intranet Page 3 of 15
4 WHO pain relief ladder 5 Paracetamol mg/kg/dose every 6 hrs (Appendix-2A) Ibuprofen 10 mg/kg/dose every 8 hrs (Appendix-2B) Reduced dose morphine micrograms/kg every 6 hours (Appendix-2C) If pain is mild or moderate and pain relief is acceptable with oral analgesia as above, patient can be managed at home with appropriate follow up arranged in the Paediatric Haematology clinic. If pain is severe and/or failed treatment with paracetamol, ibuprofen and reduced dose oral morphine, the patient should be admitted and started on the pain protocol for severe pain (Appendix-2). Copy of complete document available from: Trust Intranet Page 4 of 15
5 Pharmacological management of acute sickle pain: Exclusions: Severe Acute Chest Syndrome Girdle Syndrome Vomiting (In these conditions, consider morphine PCA. Prompt transfer to a regional Paediatric Intensive Care Unit for exchange transfusion is necessary in acute chest syndrome. This can be discuss with the on call Paediatric Consultant/Pain team) Child attends A&E/CAU with sickle pain Assessment by Medical Team Start Protocol if Paracetamol, Ibuprofen and reduced dose morphine ( micrograms/kg) already administered 0 hour Give: Morphine Sulphate 200 microgram/kg (max 10 mg) 10 mg/5ml liquid strength (Oramorph) start dose. Or IV Morphine sulphate 100 microgram/kg Single Dose AND Regular Paracetamol (15 20 mg/kg) 6 hourly and Regular Ibuprofen 10 mg/kg 8 hourly Consider PR or IV Paracetamol if the patient is vomiting (Appendix-2A) If pain is controlled at any stage refer to the last box of this algorithm 1 hour pain persists Morphine Sulphate 200 microgram/kg (max 10 mg) 10 mg/5ml liquid strength (Oramorph) (2 nd dose). 2 hours pain persists Morphine Sulphate 200 microgram/kg (max 10 mg) 10 mg/5ml liquid strength (Oramorph) (3 rd dose). 3 hours pain persists Analgesia unacceptable Analgesia acceptable Morphine PCA (Bleep Pain team (day time)/ Anaesthesia SpR on call (out of hours) Analgesia unacceptable Morphine Sulphate 200 microgram/kg (max 10 mg) 10 mg/5ml liquid strength (Oramorph)(4 th Dose) Analgesia acceptable Continue Morphine Sulphate 200 microgram/kg (max 10 mg) 10 mg/5ml liquid strength (Oramorph) PRN 4 hourly Copy of complete document available from: Trust Intranet Page 5 of 15
6 Refer to Appendix-2 (A - D) for doses Observation: Monitor the following: 1. Temperature/ pulse rate/blood pressure/respiratory rate/oxygen saturation 2. Pain 3. Sedation (AVPU) 4. Strict fluid balance chart/urine output 5. Vital signs to include respiratory rate and oxygen saturation every 20 min until pain controlled and stable; then every 2 hrs (Appendix- 4C). If respiratory rate<10/min, omit maintenance dose of opioid analgesia and seek medical assistance immediately - attention to ABC. Reversal of Opiate induced respiratory depression: Child 1month -12 years: Naloxone 5-10 microgram/kg, if response inadequate, give subsequent dose of 100 micrograms/kg (max 2 mg). Child years: Naloxone micrograms/kg, if response inadequate gives subsequent dose of 100 micrograms every 2 mins. Other medication: Laxative(C): PO Lactulose/Movicol.(Appendix-3A) Antipruritic: Chlorphenamine PRN (Appendix-3B) Antiemetic: Metoclopramide Hydrochloride PRN (Appendix-3C) Further investigation and monitoring: FBC (C), U&Es, Urea and Creatinine, Group and save on admission Other investigations should be dictated by clinical presentation Blood, urine culture (febrile, rigors, hypotensive), throat swab (cough) and CRP (febrile). CXR (febrile, breathless, tachypnoea, chest pain, chest signs, reduced O2 Saturation) Blood Gas (SaO2<95%, unexplained drowsiness) Liver function test(abdominal pain, increased jaundice), LDH Reticulocytes (Hb lower than normal/falling) Abdominal ultrasound scan (abnormal LFTs, abdominal pain, splenomegaly) Parvovirus B19 serology (reticulocytopenia) CT/MRI brain (Seizure, Transient Ischaemic Attack, Stroke, Severe Headache) Copy of complete document available from: Trust Intranet Page 6 of 15
7 Limb radiograph should not be performed unless there is history of trauma, persistent pain or unexplained swelling. Sickling can cause localised, painful swelling, bone infarcts. The differential diagnosis of osteomyelitis needs to be considered. MRI may help in diagnosis. Further management: Fluid Management: Attention to strict fluid balance. Ensure normal maintenance fluid intake orally if not dehydrated/no continued fluid loss. If not tolerated orally, NG/IV fluid administration required (Appendix- 4C). Hyperhydration (150% maintenance) tried in moderate/severe painful crisis-selected cases discuss with on call Consultant. Oxygen: Administer oxygen to maintain saturation more than 95% (Appendix- 4C). Beware of increasing oxygen requirement to maintain saturations >95% as this could be a sign of impending acute sickle chest syndrome- a medical emergency. Antibiotics: Patients with sickle cell disease are more susceptible to Streptococcus Pneumoniae Haemophilus Influenzae B, Meningococcus and Salmonella species. All children should already be on Penicillin prophylaxis. Broad spectrum antibiotics should be started if febrile (>38 degree C), generally unwell, has chest symptoms and signs, infection suspected for some other reason (Appendix- 4C). Start IV Ceftriaxone 80mg/kg; add PO Clarithromycin if chest symptoms or signs present. If patient is receiving iron chelation and presents with abdominal pain/diarrhoea: Take blood and stool cultures. Start Ciprofloxacin (to cover Yersinia). Stop iron chelation. Blood Transfusion: Note: Please discuss with on call Paediatric/Haematology Consultant if blood top up /exchange transfusion is required(paediatric exchange transfusions should take place in a PICU setting at Addenbrookes). Copy of complete document available from: Trust Intranet Page 7 of 15
8 Blood transfusion is required for symptomatic anaemia (unexplained tachycardia, tachypnoea, fatigue) not as a treatment for pain (Appendix-4). Transfuse if Hb has fallen more than 2 g/dl and is below 5 g/dl with a low reticulocyte count (<100x10 9 /l) with sickle cell negative blood transfusion. If blood transfusion is required, the possibility of sequestration (hepatic, splenic) and parvovirus infection should be considered. Exchange Transfusion is indicated in cerebrovascular accident, severe chest crisis and multiorgan failure. When blood is requested, sickle negative blood should be ordered. Liaison with duty Paediatric Haematologist Addenbrookes Hospital Patients with sickle cell disease are largely managed at NNUHFT, however if exchange transfusion is required, this will be performed by the Paediatric Haematologists at Addenbrookes Hospital within the PICU setting. Patients with HBSS are managed within the North Middlesex Haemoglobinopathy network and the point for local contact for NNUHFT is to Addenbrookes Hospital sub-network group. Inform Dr Ponnampalam or Dr Soman of child s admission to Buxton ward. It is important that Addenbrookes Hospital Paediatric Haematologists are informed of all admissions where children with HBSS are unwell with an oxygen requirement to maintain saturations >95% (or increasing oxygen requirement), signs or symptoms of a pneumonia (can mimic acute chest crisis), sequestration crisis or any patient requiring HDU care on Buxton. This constitutes a medical emergency. Early recognition and transfer of sick children known to have HBSS should be of high clinical priority and improves outcomes. Possible acute complications 1. Acute Chest Syndrome Beware of the possibility of acute chest syndrome in patients with acute painful sickle cell episode if any of the following are present at any time from presentation to discharge: Abnormal respiratory signs/symptoms Chest pain Fever Oxygen saturations of <95% or a rising oxygen requirement Copy of complete document available from: Trust Intranet Page 8 of 15
9 2. Acute Stroke 3. Aplastic crisis (check Parvovirus B19 serology) 4. Infections 5. Osteomyelitis 6. Splenic sequestration Pre discharge check list 1. Check that the patient has follow up in Dr Ponnampalam/Dr Lyall joint Paediatric Haematology OPD within 4 weeks ( liaise with Dr Ponnampalam s secretary on ext 3622) 2. Advise on oral fluid intake and analgesia including clear dosage and frequency of administration. Note: oral dose morphine as TTO should reflect the reduced dose regime only-prescribe as TTO for 3 days only 3. Check on prophylactic Penicillin BD and Folic acid OD 4. Check has sickle cell card (contact Dr Jo Ponnampalam s secretary Ext 3622 if required) 5. Inform either Dr Ponnampalam/Dr Soman of child s attendance/admission Clinical audit standards 1. Aim to assess patient for pain within 10 minutes of admission. 2. Aim for patient to receive analgesia within 30 minutes of admission(c). 3. Aim for adequate oral or intravenous hydration to be established within 30 minutes. 4. Aim for pain to be controlled to an acceptable level within 60 minutes(c). 5. The patient should be kept warm and offered reassurance. 6. Maintain oxygen saturation 95%(C). Summary of development and consultation process undertaken before registration and dissemination The authors listed above on behalf of the paediatric directorate have developed this guideline after a comprehensive literature research and discussions with paediatricians, anaesthetists, pain team, nursing staff and pharmacist. The final version was endorsed by the Paediatric clinical guidelines group. Distribution list/ dissemination method This guideline will be distributed to A&E, CAU, Buxton ward, CDW and placed on the intranet. Copy of complete document available from: Trust Intranet Page 9 of 15
10 References/ source documents 1. Jean L. Raphael, Krystal Harvey and Kent Stobart -The Cochrane Library and sickle cell disease: an overview of reviews. Evid.-Based Child Health 2: (2007) 2. Dunlop RJ, Bennett KCLB. Pain management for sickle cell disease (Review). The Cochrane Database of Systematic Reviews. Issue 2. Art No,: CD pub2. DOI: / CD pub2. (2006) tml 3. David Rees, Denmark Hill Guidelines for management of the acute painful crisis in sickle cell disease (2003) British Journal of Haematology, 2003, 120, NICE clinical guideline-sickle cell acute painful episode 5. WHO pain ladder 6. BNF for children 2013/ Royal London Hospital Guideline on Management of painful crisis in sickle cell disease. Copy of complete document available from: Trust Intranet Page 10 of 15
11 Appendix-1 Category Face Legs Activity Cry Pain Assessment Tool for Infants and Toddlers No particular expression or smile (FLACC Behavioural Scale) Scoring Occasional grimace or frown, withdrawn, disinterested Normal position or relaxed Lying quietly, normal position, moves easily No cry (awake or asleep) Consolability Content, relaxed Uneasy, restless, tense Squirming, shifting back and forth, tense Moans or whimpers; occasional complaint Reassured by occasional touching, hugging or being talked to, distractible Frequent to constant quivering chin, clenched jaw Kicking, or legs drawn up Arched, rigid or jerking Crying steadily, screams or sobs, frequent complaints Difficult to console or comfort Each of the five categories (F) Face; (L) Legs; (A) Activity; (C) Cry; (C) Consolability is scored from 0-2, which results in a total score between zero and ten: 0 = No Pain (0) 1-3 = Mild Pain (1) 4-7 = Moderate Pain (2) 8-10 = Severe Pain (3) Pain Assessment Tool for Children aged 3-7 Years (Modified Wong and Baker) Appendix-2 Copy of complete document available from: Trust Intranet Page 11 of 15
12 A. Paracetamol By mouth Child 1 3 months mg every 8 hours as necessary; for severe symptoms 20 mg/kg as a single dose then mg/kg every 6 8 hours; max. 60 mg/kg daily in divided doses Child 3 12 months mg every 4 6 hours (max. 4 doses in 24 hours); for severe symptoms 20 mg/kg every 6 hours (max. 90 mg/kg daily in divided doses) for 48 hours (or longer if necessary and if adverse effects ruled out) then 15 mg/kg every 6 hours Child 1 5 years mg every 4 6 hours (max. 4 doses in 24 hours); for severe symptoms 20 mg/kg every 6 hours (max. 90 mg/kg daily in divided doses) for 48 hours (or longer if necessary and if adverse effects ruled out) then 15 mg/kg every 6 hours Child 6 12 years mg every 4 6 hours (max. 4 doses in 24 hours); for severe symptoms 20 mg/kg (max. 1 g) every 6 hours (max. 90 mg/kg daily in divided doses, not to exceed 4 g) for 48 hours (or longer if necessary and if adverse effects ruled out) then 15 mg/kg every 6 hours; max. 4 g daily Child years 500 mg every 4 6 hours; for severe symptoms 1 g every 4 6 hours (max. 4 doses in 24 hours) By rectum Child 1 3 months mg every 8 hours as necessary; for severe symptoms 30 mg/kg as a single dose then 20 mg/kg every 8 hours; max. 60 mg/kg daily in divided doses Child 3 12 months mg every 4 6 hours as necessary (max. 4 doses in 24 hours); for severe symptoms 40 mg/kg as a single dose then 20 mg/kg every 4 6 hours (max. 90 mg/kg daily in divided doses) for 48 hours (or longer if necessary and if adverse effects ruled out) then 15 mg/kg every 6 hours Child 1 5 years mg every 4 6 hours as necessary (max. 4 doses in 24 hours); for severe symptoms 40 mg/kg as a single dose then 20 mg/kg every 4 6 hours (max. 90 mg/kg daily in divided doses) for 48 hours (or longer if necessary and if adverse effects ruled out) then 15 mg/kg every 6 hours Child 5 12 years mg every 4 6 hours as necessary (max. 4 doses in 24 hours); for severe symptoms 40 mg/kg (max. 1 g) as a single dose then 20 mg/kg every 6 hours (max. 90 mg/kg daily in divided doses) for 48 hours (or longer if necessary and if adverse effects ruled out) then 15 mg/kg every 6 hours Child years 500 mg every 4 6 hours; for severe symptoms 1 g every 4 6 hours; max. 4 g daily in divided doses By intravenous infusion over 15 minutes Child body-weight under 10 kg 7.5 mg/kg every 4 6 hours; max. 30 mg/kg daily Child body-weight kg 15 mg/kg every 4 6 hours; max. 60 mg/kg daily Child body-weight over 50 kg 1 g every 4 6 hours; max. 4 g daily Copy of complete document available from: Trust Intranet Page 12 of 15
13 B. Ibuprofen By mouth 1 3 months 5 mg/kg 3 4 times daily 3 6 months 50 mg 3 times daily; max. 30 mg/kg daily in 3 4 divided doses 6 months 1 year 50 mg 3 4 times daily; max. 30 mg/kg daily in 3 4 divided doses 1 4 yrs 100 mg 3 times daily; max. 30 mg/kg daily in 3 4 divided doses 4 7 yrs 150 mg 3 times daily; max. 30 mg/kg daily in 3 4 divided doses 7 10 yrs 200 mg 3 times daily; max. 30 mg/kg (max. 2.4 g) daily in 3 4 divided doses yrs 300 mg 3 times daily; max.30 mg/kg (max. 2.4 g) daily in 3 4 divide doses yrs initially mg 3 4 times daily; increased if necessary to max. 600 mg 4 times daily; maintenance dose of mg 3 times daily may be adequate C. Morphine Sulphate By mouth or by rectum Reduced dose oral morphine all ages micrograms/kg/dose 6 hourly Otherwise: Child 1 3months initially micrograms/kg every 4 hours, adjusted according to response Child 3-6 months micrograms/kg every 4 hours, adjusted according to response Child 6-12 months 200 micrograms/kg every 4 hours, adjusted according to response Child 1 2 years initially micrograms/kg every 4 hours, adjusted according to response Child 2 12 years initially micrograms/kg (max. 10 mg) every 4 hours, adjusted according to response Child years initially 5 10 mg every 4 hours, adjusted according to response By intravenous injection over at least 5 minutes Neonate initially 50 micrograms/kg every 6 hours, adjusted according to response Child 1 6 months initially 100 micrograms/kg every 6 hours, adjusted according to response Child 6 months 12 years initially 100 micrograms/kg every 4 hours, adjusted according to response Child years initially 2.5 mg every 4 hours, adjusted according to response Copy of complete document available from: Trust Intranet Page 13 of 15
14 Appendix-3 Movicol Paediatric Plain By mouth Child 1 6 yrs 1 sachet daily; adjust dose to produce regular soft stools (max. 4 sachets daily) Child 6 12 yrs 2 sachets daily; adjust dose to produce regular soft stools (max. 4 sachets daily) Administration Mix content of each sachet in quarter of a glass (approx ml) of water Movicol Lactulose By mouth Child years 1 3 sachets daily in divided doses usually for up to 2 weeks; maintenance, 1 2 sachets daily Administration Mix content of each sachet in half a glass (approx. 125 ml) of water By mouth 1 month 1 yr 2.5 ml twice daily, adjusted according to response 1 5 yrs 5 ml twice daily, adjusted according to response 5 10 yrs 10 ml twice daily, adjusted according to response yrs 15 ml twice daily, adjusted according to response Chlorphenamine Maleate By mouth 1 month 2 years 1 mg twice daily 2 6 years 1 mg every 4 6 hours, max. 6 mg daily 6 12 years 2 mg every 4 6 hours, max. 12 mg daily years 4 mg every 4 6 hours, max. 24 mg daily Metocopramide Hydrochloride By mouth, or by intramuscular injection or by intravenous injection over 1 2 minutes Neonate 100 micrograms/kg every 6 8 hours (by mouth or by intravenous injection only) Child 1 month 1 year and body-weight up to 10 kg 100 micrograms/kg (max. 1 mg) twice daily Child 1 3 years and body-weight kg 1 mg 2 3 times daily Child 3 5 years and body-weight kg 2 mg 2 3 times daily Child 5 9 years and body-weight kg 2.5 mg 3 times daily Child 9 18 years and body-weight kg 5 mg 3 times daily Child years and body-weight over 60 kg 10 mg 3 times daily Note Daily dose of metocolopramide should not normally exceed 500 micrograms/kg Copy of complete document available from: Trust Intranet Page 14 of 15
15 Appendix-4 Classification of grades of recommendations A Requires at least one randomized controlled trial as a part of a body of literature of overall good quality and consistency addressing specific recommendation B Requires the availability of well-conducted clinical studies, but no randomized clinical trials on the topic of recommendation C Requires evidence obtained from expert committee reports or opinions and or clinical experiences of respected authorities. Indicates an absence of directly applicable clinical studies of good quality. Copy of complete document available from: Trust Intranet Page 15 of 15
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