Original Article

Management of Pain in Leukemic Children using the

WHO Analgesic Ladder
M.G. Geeta, P. Geetha, V.T. Ajithkumar, P. Krishnakumar, K. Suresh Kumar and Lulu Mathews

Department of Pediatrics, Institute of Maternal and Child Health, Medical College, Calicut, Kerala, India

ABSTRACT
Objective. To ascertain the effectiveness of WHO analgesic ladder in pain management in children with leukemia.

Methods. Children with leukemia who were referred to a pain and palliative care clinic attached to the Department of
Pediatrics of a medical teaching hospital during a period of 6 months, were included in the study.

Results. Thirty nine (39) children, who constituted 64% of children on treatment for leukemia, required referral to pain and
palliative care services during the study period. Of these 92% had Acute Lymphocytic Leukemia (ALL) and 8% had Acute Non
Lymphocytic Leukemia (ANLL). 95% of children had nociceptive pain and 5% had neuropathic pain. Step – 1 analgesia was
effective in 12 (31%) children and 21 (54%) could be managed with Step – 2 analgesia. Step – 3 analgesia was required in
only 6 (15%) children. Step 3 analgesia was required in children with neuropathic pain and bone pain.

Conclusions. WHO analgesic ladder is effective in managing pain in children with leukemia. Majority of cases of cancer pain
in children could be managed by the treating physician using non-opioids, weak opioids and adjuvants as per the WHO
guidelines. Children with bone pain and neuropathic pain may require referral to specialist services and use of strong opioids
like morphine. The study emphasizes the need for establishing specialist pain management services in all centres where
children with cancer are treated. [Indian J Pediatr 2010; 77 (6) : 665-668] E-mail: geetakkumar@gmail.com

Key words: Children; Leukemia; Pain; WHO analgesic ladder

Pain is the commonest and most distressing symptom in
children with leukemia. Pain in children with leukemia
may be either disease related or due to treatment.1
The World Health Organization has developed
guidelines for the management of cancer pain in children
based on a three step analgesic ladder (Fig. 1). WHO
analgesic ladder Step – 1 is for mild pain and includes use
of non opioids, Step-2 is for moderate pain and consists of
weak opioids and Step-3 is for severe pain and involves
use of strong opioids.2
General pediatricians are well equipped to manage
mild and moderate pain (Step-1 and 2 of the WHO
analgesic ladder). Since the availability of morphine is
restricted, specialist reference may be needed for Step-3
analgesia. Hence it is ideal to have a separate referral
service for pain management in all hospitals where
children with leukemia are treated.
Correspondence and Reprint requests : Dr. Geeta Govindaraj,
Assistant Professor, Department of Pediatrics, Medical College,
Calicut, Kerala-673008, India.
[DOI-10.1007/s12098-010-0053-x]
[Received September 29, 2009; Accepted December 18,
2009]
The present study was conducted to ascertain the
effectiveness of the WHO analgesic ladder in
management of pain in children on treatment for acute
leukemia and to ascertain the need for Step-3 analgesia.
MATERIAL AND METHODS
The study was conducted in the pain and palliative care
clinic at the Department of Pediatrics, Medical College,
Calicut. The pain and palliative care clinic started
functioning in January 2009 and is a joint venture of the
Department of Pediatrics, Medical College, Calicut and
the Institute of Palliative Medicine, Calicut. Children with
leukemia and other chronic illnesses who require pain
management are referred to the pain and palliative care
clinic. The clinic is conducted by two assistant professors
in pediatrics with special training in palliative medicine,
a staff nurse trained in palliative care, a social worker and
community volunteers including mothers who had lost
children due to leukemia.
In the pain and palliative care clinic detailed clinical
examination is done for every child after recording the
family history, psychosocial history and clinical history.

Indian Journal of Pediatrics, Volume 77—June, 2010 665

 M.G. Geeta et al
The nature, cause, severity, duration and effect of pain
on the child are recorded. Children with acute leukemia
who were referred to the pain and palliative care clinic
for pain management during the six month period from
January 2009 to June 2009 were included in the study.
Pain is classified as nociceptive pain or neuropathic
pain depending upon the nature and cause of pain.
Nociceptive pain is further classified as visceral pain
(bowel, bladder, capsular, and cardiac) and somatic pain
(bone pain, pain due to soft tissue involvement like
abscess, mucositis).3 Assessment of severity of pain is
done using the numerical rating scale for older children
and Wong Baker faces scale 4 and mother reports for
younger children. Children are treated for pain using non
opioids, weak opioids or strong opioids depending on the
type and severity of pain. Frequent reviews of the
children determine whether the analgesia needs to be
stepped up or adjuvants added. Adverse effects are
carefully looked for.
RESULTS
During the study period 39 children with acute leukemia,
were referred to the pain and palliative care clinic for
pain management, who formed 64 % of the 61 children
undergoing treatment for leukemia in the department
during the study period. There were 28 (72%) boys and 11
(18%) girls. 36 (92%) children had ALL and 3(8 %) had
ANLL. The youngest was a one and a half year old boy
and the oldest was a 12-year-old boy. Among children
with ALL, 19 children were on induction therapy while 6
children were in the maintenance phase.11 children were
in relapse. Three children with ANLL were in remission.
The children were on treatment from the pediatric
hemato-oncology unit of the Department of Pediatrics
using standard protocol.
Of the 39 children 37(95%) had nociceptive pain
while 2 (5%) children had neuropathic pain. Among
children with nociceptive pain, 1 (3%) had visceral
pain, 34 (92%) had somatic pain and 2(5%) had both
somatic and visceral pain. Allodynia was present in 2
children with neuropathic pain. 12 (31%) children were
managed with Step-1 analgesia. Step-2 analgesia was
effective in 21 (54%) children. Only 6 (15%) children
TABLE 1. Details of Children with Leukemia who Required Step–3 Analgesia
No. Age years Sex Type of leukemia Type of pain
1 11 M L2- T cell Neuropathic
2 7 F L2- T cell Neuropathic
3 10 M L2- T cell Nociceptive
4 7 M L2- Pre B Nociceptive
5 8 M L2 Nociceptive
6 3.5 M L2- Pre B Nociceptive
666
required Step–3 analgesia. Paracetamol was the drug of
first choice in Step–1. Codeine (1mg/Kg per dose) was
the weak opioid used in Step–2 while oral morphine
sulphate (0.3mg/Kg/ dose) was the strong opioid used
in Step–3. Among the 6 children who required Step–3
analgesia, 5 were boys and one was a girl. All children
had ALL. Two had neuropathic pain and 4 had
nociceptive pain. All 6 children received 0.3 mg per Kg
of morphine sulphate 4 hourly orally as the starting
dose. In addition to morphine children with
neuropathic pain were given oral dexamethasone (4mg
once daily and tapered off in five days) and
amitryptylline (25mg at night) and ketamine as
adjuvants. Sublingual ketamine 0.15mg/Kg was used for
short duration flares of pain (breakthrough pain) Table 1.
Constipation was the only adverse effect observed in
children on opioids. Bisacodyl was co-prescribed with
opioids in all children to prevent constipation and
magnesium sulphate was required in addition to
bisacodyl in 15% of children. Drowsiness was not a
significant problem. Respiratory depression did not occur.
DISCUSSION
Prompt relief from pain is important because unrelieved
pain leads to disturbed sleep, fatigue, psychological
trauma and an increase in morbidity and mortality
among children with cancer.5 In the present sample 64 %
of children on treatment for leukemia needed referral to
pain and palliative care services and underlines the need
for better awareness of pain management issues among
physicians treating children with leukemia. Pain may be
nociceptive (somatic or visceral) or neuropathic (due to
transmission by a damaged nervous system) in origin.4
Neuropathic pain can be severe, distressing and difficult
to treat, and may be associated with diminished sensation
or allodynia (pain due to a stimulus that does not usually
cause pain). In the present sample 95% of children had
nociceptive pain whereas neuropathic pain was present in
5% cases only. This finding is in contrast to that of Misra
S et al who reported that among children with cancer,
pain was nociceptive in 31%, neuropathic in 14.3% and
mixed in 54.8%.6 This difference could be attributed to the
fact that the present sample consisted of only children
Cause Adjuvants
Peripheral neuropathy Ketamine + Amitryptylline +
due to Vincristine Dexamethasone
CNS leukemia Dexamethasone
Bone pain Nil
Fracture neck of Femur Nil
Bone metastases Nil
Fracture ileum Nil
Indian Journal of Pediatrics, Volume 77—June, 2010
 Management of Pain in Leukemic Children using the WHO Analgesic Ladder
with acute leukemia while they have included children
with other types of cancer as well. Only one third of the
children referred could be managed with Step–1 drugs
while more than half needed Step–2 drugs. This is due to
the fact that most children were referred when pain did
not respond to non opioids prescribed for pain relief.
Majority of the children who were prescribed Step-1
analgesia in the pain clinic had mucositis which
responded to aspirin gargles or local anesthetics like
lignocaine.
The WHO analgesic ladder has stood the test of time as
a simple guide for clinicians regarding pain management
in children with cancer and other chronic painful
conditions. Upto 90% of patients obtain good pain relief
using these guidelines.7 WHO ladder Step–1 is for mild
pain and includes paracetamol and NSAIDs (non-opioids)
and adjuvants. Since thrombocytopenia is a common
problem in leukemic children, it should be excluded
before prescribing NSAIDs. Adjuvants are drugs that
provide pain relief in certain situations though not
primarily analgesics. 4 These include tricyclic
antidepressants, anticonvulsants, anxiolytics,
antispasmodics and steroids. WHO analgesic ladder Step-
2 is for moderate pain and involves use of Step- 1 drugs
alongwith weak opioids like codeine, dextropro-
poxyphene and tramadol. Adjuvants may be used when
required. Step-3 is for severe pain and includes use of
strong opioids like morphine and fentanyl alongwith non
opioids and adjuvants when needed. Thus opioids are
used in Step–2 and 3 for management of moderate to
severe pain (Fig. 1).
STEP 3
Strong opioid
+/- Non- opioid +/- adjuvant
STEP 2
Weak opioid
+ Non- opioid +/- adjuvant
STEP 1
Non opioid +/- Adjuvant

with acute leukemia. Assessment of the type and severity
PAIN
Fig. 1. WHO analgesic Ladder.
The four key concepts for use of analgesia in children
are “by the ladder”, “by the mouth”, “by the clock” and
“by the child”. “By the ladder” refers to the WHO ladder
as mentioned. Progressively stronger analgesics should
be used based on the child’s level of pain. It is important
that analgesics should be administered on a regular basis
depending on the drug’s duration of action and not s. o.
s. The drugs should be administered preferably by mouth
Indian Journal of Pediatrics, Volume 77—June, 2010
so that the fear of injections and consequent denial of
pain by the child is avoided. The dosage of drugs used
for pain management should be individualized.
Experience of treating neuropathic pain in children
with cancer is limited.5 Neuropathic pain and bone pain
may be partially resistant to opioids.4 Adjuvants may be
necessary in these situations. In the present sample the
two children with neuropathic pain responded well to
opioids and adjuvants. Antidepressants work by
facilitating descending inhibitory pain pathways.
Corticosteroids are effective due to the effect of reducing
inflammatory sensitization of nerves or reducing edema
causing pressure on nerves. 4 Ketamine is effective in
neuropathic pain by virtue of N-methyl D-aspartate
(NMDA) receptor blockade in subanesthetic doses. The
NMDA receptor is thought to be involved in the “wind
up” phenomenon in neuropathic pain, where the
experience of chronic unrelieved pain results in nerve
fibers being trained to deliver pain signals better.4 In the
present sample 4 children with bone pain responded to
morphine and NSAIDs. (Ibuprofen and mefenamic acid).
Our experience shows that WHO analgesic ladder Step–3
is effective in relieving neuropathic pain and bone pain in
children with cancer. This finding is comparable to the
results of a study by Misra et al who found that
neuropathic cancer pain can be relieved by multimodal
treatment following WHO guidelines as majority of
cancer patients suffered multiple types of pain.8
In the present sample only 6 children with neuropathic
pain and bone pain required step- 3 analgesia which
involves use of morphine. Majority of children could be
managed with WHO analgesic ladder Step–1 and Step–2.
This indicates that majority of cases of nociceptive pain in
children could be managed by the treating physician
using non-opioids, weak opioids and adjuvants. Children
with severe pain may require referral to specialist
services, underlining the need for establishing specialist
pain management services in all centers where children
with cancer are treated.
CONCLUSIONS
Pain is a common and distressing symptom in children
of pain is important for effective management. The WHO
three step analgesic ladder is a useful tool for
management of pain in children with leukemia. In
majority of cases, pain in children with leukemia could be
managed as per the Steps–1 and 2 of the WHO analgesic
ladder. Children with neuropathic pain and bone pain
may require Step–3 analgesia where strong opioids like
morphine are used for pain relief. Hence it is ideal to have
pediatric pain and palliative care services available in
all centers where children with cancer are treated.
667
 M.G. Geeta et al
Acknowledgements
We thank Dr. A Riyaz, Professor and HOD, Department of
Pediatrics, Medical College, Calicut for permission to publish the
study. We acknowledge the help of Ms. Thripthi Jose (social
worker), Ms. Lizy Rajan (palliative care nurse) and Sr. Merlin
(palliative care nurse) for their help in collection of the data.
Contributions: MGG collected and analyzed the data and wrote the
manuscript. P G helped in collection of data and management of
children. VTA was the medical officer-in-charge of the pediatric
haemato-oncology unit and helped in patient management and data
collection. PK designed the study and helped in analysis of the data
and writing the manuscript. KSK and LM supervised patient care
and helped in study design and preparation of the manuscript.
Conflict of Interest : None.
Role of Funding Source: None.
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