Management of Sickle pain - STAPG · 2019. 12. 14. · Management of pain in Sickle Cell disease Dr Rachel Kesse-Adu Consultant Haematologist . disclosures •Novartis. Outline •SCD

Management of pain in Sickle Cell disease

Dr Rachel Kesse-Adu

Consultant Haematologist

disclosures

• Novartis

Outline

• SCD • Pathophysiology

• VOC pain • Management

• Chronic pain in SCD• Management

• Issues around pain management in SCD

Adult haemoglobin (HbA)2 a and 2 b globin chains each with a central

haem

HbA = a2b2

HbF = a2g2

HbA2= a2d2

Polymerisation of

Sickle haemoglobin

HbS

(2a2bS)

- O2+O2

Irreversibly

sickled cells

Vaso-occlusion

Low oxygen tension

Haemolysis, anaemia

Pathophysiology of Sickle Cell Anaemia

Manwani D & Frenette PS. Blood 2013;122(24):3892–98

Clinical features

Brain:

CVA

Skin

Ulcers

Liver:

Sequestration

Hepatopathy

Jaundice

Spleen:

Infarction till hyposplenic

Sequestration

Eyes:

Retinopathy

Bone:

Infarcts

Osteomyelitis

Avascular necrosis

GU:

Priapisim

Bone:

Infarcts

Osteomyelitis

Lungs:

Sickle lung

Pulmonary

hypertension

Chest crisisAnaemia

Kidneys:

Proteinuria

Papillary necrosis

Renal failure

SCD is characterized by chronic inflammation

iNKT cell, invariant natural killer T cell1. Zhang D et al. Blood 2016;127:801–09Figure reproduced with permission from Zhang D et al. Blood 2016;127:801–09

Activated monocytes, iNKT cells and

endothelial cells promote inflammation1

Haemolysis of sickle-shaped RBCs results in

production of proinflammatory

cytokines1

1

1

Proinflammatory cytokines activate endothelial cells,

platelets and leucocytes, causing

increased expression of adhesion molecules1

2

Numerous adhesion molecules contribute to vaso-

occlusion

Sickled RBCs and platelets adhere to leucocytes, forming

heterocellularaggregates that

contribute tovaso-occlusion1,3

1. Zhang D et al. Blood 2016;127:801–09; 2. Wagner DD, Frenette PS. Blood 2008;111:5271–81; 3. TelenMJ. Blood 2016;127:810–19Figure reproduced with permission from Zhang D et al. Blood 2016;127:801–09

Vaso-occlusion is exacerbated by cycles of tissue ischaemia and reperfusion

ROS

Blood flow

to tissue

ROS

Vaso-occlusion and ischaemia

ROS, reactive oxygen species1. Rees DC et al. Lancet 2010;376:2018–31; 2. Habara A, Steinberg MH. Expt Biol Med 2016;241:689–96; 3. Zhang D et al. Blood 2016;127:801–09

Chronic inflammation promotes

vaso-occlusion3

Free radicals cause oxidative damage to the endothelium, promoting

cell adhesion2

Cyclic

Blood flow to

tissue

ROS

ROS

Reperfusion after vaso-occlusion

Chronic inflammation results in increased

synthesis of inflammatory cytokines1

Activated vascular oxidases produce

free radicals1,2

PAIN

Acute Vaso Occlusive Crisis (VOC)

• No diagnostic tests

• No universally accepted definitions but potential one:• Patient with SCD

• Pain lasts at least 2 hours

• Started in last 10 days

• One physical sign (palpation, movement cause pain, or decreased ROM)

• Can’t be explained by SCD complication (leg ulcer, AVN etc)

• May occur with or without chronic SCD pain

Joshua J. Field1, Samir Ballas2, Claudia M. Campbell3, Lori E. Crosby4, Carlton Dampier5, Deepika S. Darbari6, Wally R. Smith7, William T. Zempsky.8 AAAPT Diagnostic Criteria for Acute Sickle Cell Disease Pain. Manuscript under review.

Acute VOC

~30% of adult

patients have some

pain 95% of the

time2

~14% of adult

patients are in pain

<5% of the time2

“Unbearable”3

“A pain that I wouldn’t

wish on my worst enemy”3

“Excruciating”3

“Like being hit by a truck

and getting run over”3

“Stabbing”3

VOCs cause up to

95% of hospital

admissions for SCD patients1

1. Ballas SK et al. Am J Hematol 2005;79:17–25; 2. Smith WR et al. Ann Intern Med 2008;148:94–101; 3. AdegbolaMA et al. J Natl Black Nurses Assoc 2012;23:16–23

VOC has distinct phases

Resolving phase

Established phaseInitial phase

Prodromal phase

Cat

ego

rica

l pai

n s

cale

Common timing for onset of

complications

eg ACS, MOF, relapse, death

2. Initial phase1

▪ Peak pain severity▪ Increased anxiety

3. Established phase1

▪ Peak pain severity maintained▪ Signs of joint effusion and

inflammation

DayACS, acute chest syndrome; MOF, multiorgan failure1. Ballas SK et al. Blood 2012;120:3647–56Figure reproduced with permission from Ballas SK et al. Blood 2012;120:3647–56

4. Resolving phase1

▪ Pain severity decreases

0

1

2

3

4

5

6

7

8

9

10

-2 -1 0 1 2 3 4 5 6 7 8 9 10

1. Prodromal phase1

▪ Symptoms include numbness, paresthesia, and aches

▪ May be asymptomatic

NICE guidance

▪ 1. http://publications.nice.org.uk/sickle-cell-acute-painful-episode-management-of-an-acute-painful-sickle-cell-episode-in-hospital-cg143/recommendations

• regard the patient (and/or their carer) as an expert in their condition

• take into account any analgesia taken by the patient before presentation

• Offer analgesia within 30 minutes • ensure that the drug, dose and administration route are suitable for the

severity of the pain and the age of the patient

• refer to the patient's individual care plan if available

• Assess the effectiveness of pain relief:• every 30 minutes until satisfactory pain relief has been achieved, and at least

every 4 hours thereafter using an age-appropriate pain scoring tool

• Encourage the patient to use their own coping mechanisms

Acute VOC

• Audit time to analgesia in A+E 1-2x year • Aim is >90% • Usually 30 – 60%• Day units usually better (80-100%)

• Managed in most centres by sickle teams but paediatric teams more successfully engaged the acute pain teams

• Inpatient stays may involve high use of opiates

• Better at instituting weaning regimens

• Less MR preparations

Discharge

• Step down pharmacological treatment as episode resolves

• Discharge information• how to obtain specialist support

• how to obtain additional medication

• how to manage any potential side effects

At GSTT

• Individualised analgesia plan on EPR

At GSTT

• Most admitted SCD patients • s/c bolus opiate regimen average doses 5-10mg Morphine sulphate immediate release 2 hourly• We avoid IV dosing – poor veins and adds delay to receiving effective analgesia

• Convert to PCA if admitted especially if requiring frequent doses or pain difficult to manage

• Escalate to HDU for monitoring if requiring 1.5-2x pain plan doses

• Switch to oral 24 hours before discharge

• Discharge with a wean to original baseline plab• Avoid opiate creep

• Younger patients much less likely to be on a parenteral opiate acute analgesia plan

Chronic pain

Recurrent crises with no intermediate pain1

Chronic pain1

Prodromal Initial Established Resolving Initial Established Resolving

Crisis day Crisis day100 98765421–1–2 3

2

4

6

10

8

1098765421–1–2 3

Prodromal Initial Established Resolving Initial Established Resolving

Crisis day Crisis day100 98765421–1–2 3

2

4

6

10

8

1098765421 3

Cat

ego

rica

l pai

n s

cale

1. Ballas SK et al. Blood 2012;120:3647–56Figures reproduced with permission from Ballas SK et al. Blood 2012;120:3647–56

Cat

ego

rica

l pai

n s

cale

Chronic pain

Avascular necrosis

Neuropathic pain

Central sensitization

Vertebral body

collapse

Arthropathy nociceptive (vasculopathic, inflammatory)

Above

water

Submerged

The Iceberg: Proportion of Days in Pain, Crisis, Utilisation R

*Percentage of days. Utilization= utilization with or without crisis or pain; Crisis= crisis without utilization; Pain= pain without crisis or utilization. Adapted from Smith WR, et. al. Ann Intern Med 2008 Jan 15, 148(2):94-101

39.3%

44.1%

13.1%

3.5%

Intensity Mean Std

Dev

Utilization 6.5 2.3

Crisis w/o utilization 5.5 2.1

Pain w/o crisis, util. 4.2 2

No Pain 0 0

PiSCES

Chronic pain management challenges n SCD

• Underlying condition associated with acute unpredictable and unpreventable pain episodes

• How to differentiate • Both for physicians and patients

• Which analgesia? When? How much? How long for?

GSTT - MDT approach

• Pain specialist

• Haematologists

• Psychologist

• Social worker

• Community Nurse

• Specialist nurses – Pain and Haematology

• Virtual pain MDT clinic

Case

• 28y female HbSS, Endometriosis

• Multiple admissions with pain since paeds

• Hydroxycarbamide (HC) started in paeds

• Switched to EBT 2009 for 1 year: no impact on admissions

• Recommenced HC 2010

• Opiate protocol on admission: • 10mg s/c IR morphine Sulphate 2-4 hourly in 2013

• 20mg s/c IR morphine Sulphate 2-4 hourly in 2017

• Observations, Labs frequently at steady state during inpt stays

• Chronic pain: back, pelvis and lower limbs – similar site on admission

• Twin pregnancy 2016: switched back to EBT

• Delivered by emergency csection for PET at 34 weeks

• Babies admitted to NICU but both healthy babies

• Total Admissions (day unit/A+E) Jul 2016/17: 50

• Switched back to transfusion program July 2017 disease severity

• Total Admission (day unit/A+E) Jul 2017/18: 41

•Issues:•Top attender to our service

• Increasing analgesia requirements to manage pain episodes

•?is this acute or chronic pain management

• MDT approach• Psychology, Social services, Gynaecology, Pain team, Sickle team

• Encouragement to attend OPA whilst inpatient

• Liaise with GP and Hospital pharmacy:• Calculate opiates + other analgesia prescribed per month pre opa consult

• Discussed in Virtual pain MDT clinic

• Initial joint consult with psychology team present – Aug 2017• Medical directed review 1st

• Sites of pain

• Types of pain

• When is pain present/worst, is she ever pain free?

• Pain management at home – what works best

• Other issues as she reports to be important• Multiple social stresses – largely single parent, housing issues

• Effect of this on pain experience?

• Psychology review: mood, worries, concerns

• Agree to recommence chronic EBT program

• Once established on EBTs to wean analgesia doses received on acute admission

• initially to receive s/c for 1st 24hours only then switch to oral

• Wean modified release opiate analgesia off

• Aim to manage pain with simple analgesia

• use immediate release opiates only for breakthrough pain

• Re-engage with psychology

• Case discussed with benefits worker and support letters for housing

• Improved communication with GP

• April 2018 – progress•Medical:

•Sickle management S% well controlled – highest 25%;

•Daily pain: back, hips and lower limbs.•Gynae plan noted – investigative largely

•Analgesia• off MR preparations and total opiate use/month reduced significantly

• recent (2019) reduction in acute presentations and marked decrease in length of stay

•Other pain management modalities• Facet joint injections – no sites identified

•Neuropathic options – Amitriptyline,

• TENS machine

•Psychology support•Multiple stresses remain, children now in nursery May 2018

• Commenced anti-depressant – Sertraline

•Single prescriber for opiates

Summary

• SCD inherited condition associated with multiorgan complications but most significantly pain

• Acute pain in sickle associated with the vaso-occlusive crisis • Manged by haematologists

• Chronic pain in common in SCD variety of causes

• Management difficult• MDT and an individualised patient approach

Thank You