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PAIN MANAGEMENT BY WHo STEP lADDER PATTERN PRoToCol
IN CASES oF CERVICAl CANCER
Namrata3, Singh U2, Srivastava AN1, Singh N2, Shankhwar PL2
Professor & Head, Department of Pathology, Era’s Lucknow Medical College & Hospital, Lucknow1
Professor, Department of Obstetrics & Gynaecology, KGMU, Lucknow2
Senior Resident, Department of Maternal and Reproductive Health,
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow3
Address for correspondence
To assess pain in cases of cancer cervix and to evaluate the response to pain management Dr. Namrata
according to WHO step ladder pattern in cases of cancer cervix, total 209 carcinoma cervix (MBBS)
riveni Nagar III,
diagnosed and admitted case were recruited in the study. Baseline pain score was measured for MD 538/925 TSitapur Road, Lucknow
each patient. For mild to moderate pain (VAS ≤ 7) , step 1 analgesic, NSAID, diclofenac sodium Pin – 226020
(50 mg TDS) was prescribed. Pain scores were reevaluated after 48 hrs and change of score was Phone : 91 9415 118848,
recorded. If pain persisted (same score), worsened (score increased) or score decreased but with E–mail – firstname.lastname@example.org
a VAS score of > 4 , case was considered as non responder and patient was switched to step 2
analgesic. Step 2 was also applied directly to patients presenting with severe pain ( VAS >7) at
the time of recruitment. Drugs used in step 2 was oral tramadol (50 mg QID ) along with Diclofenac ( 50 mg TDS) . VAS Score
was reevaluated after 48 hrs. If score still remained above 4; adjuvant analgesics (Amitryptiline 25–75 mg OD, Prednisolone 5mg
BD – 10 mg/day) were added to step 2. Step 2 non responders were treated with step3 protocol. In step 3, tab morphine (10 mg
BD upto maximum 30 mg BD) was given after stopping all other drugs . After 48 hrs, scores were re evaluated; if scores remained
>4; adjuvant analgesics ( Amitryptiline 25–75 mg OD, Prednisolone 5mg BD – 10 mg/day ) were added. After 48 hrs if still pain
scores did not decrease to <4, case was declared as failure . The WHO algorithm was followed as per the response of the patients.
Outcome showed decrease in pain score using Visual Analogue Scale Score. 209 patients were enrolled in the study. 60 patients
had no pain at baseline. Out of 149 patients with pain, 44.9 % (67) patients achieved complete pain relief at step 1. Out of the
remaining 82 patients , 5 were lost to follow up. 49.3 % (38) achieved complete relief at step 2 . Only 39 patients did not reach
score of zero after step 2 but 35 (89.7%) out of them achieved complete relief after step 3. Out of 142 patients ( excluding lost
to follow up ), 2 cases were declared as failure. Among these failure cases, one of them had metastasis of femur and symphysis
pubis; bisphosphonates were started. Other patients had bladder and bowel involvement diagnosed on repeat cystoscopy. This
WHO guideline implementation study supports use of algorithm in decision making for cancer pain management. Following
the same we were able to achieve effective pain relief in 96% of our patients with failure rate of only 4%. It further helped to
reduce patient’s agony and improved the quality of life.
Key Words: Cancer cervix , Pain , Treatment.
INTRoD UCTIoNoccurs from many causes like somatic, visceral, neuropathic
Pain is a subjective multidimensional experience unique to and bone pain ( Ashby 1992 ) . Ninety percent of pain in
an individual, with a potential impact on function, status and cancer cervix is a complex resulting from the tumor itself,
quality of life. Yet it is one of the most common unattended in which 70% of pain develops from tumor invading or
and unsolved problem for cancer patients. Cancer cervix compressing uterosacral ligament and sacral plexus, and 20%
is one of the leading cause of cancer death among women of cancer pain is related with its treatment ( radiation and
worldwide. Incidence of new cancer patients in India is about chemotherapy related neurotoxicity). Rest 10% of pain is due
100,000 per year and 70% or more of these are stage 3 or to unrelated illness. Common sites of pain in cancer cervix
higher at the time of diagnosisEJMR (Venugopal T C 1995). Pain are back, lower abdomen, flank, buttocks and perineum.
is a debilitating symptom associated with cancer cervix. It Pain can be pressure like, dull aching , burning , cramping or
occurs in 25–50% patients with newly diagnosed malignancy, lancinating (Saphner 1989).
in more than 75% of those with advanced disease, and in WHO recommended a stepladder pattern algorithm as a
33% of those undergoing treatment (Van den Beuken 2007) . guideline for pharmacological management of cancer pain in
Pain in patients with cancer cervix is a complex process that 1986 ( WHO 1996 ) which was updated in 1996. It describes
? 2014 JOURNAL OF MEDICAL RESEARCHVol.1 No.1Vol.1Jul.–Dec. 2014ERA’S JOURNAL OF MEDICAL RESEARCHJul.–Dec. No.1ERA’S
three step progression from the use of nonopoid medication PAIN MANAGEMENT
(acetaminophen, dipyrone, NSAIDs) to weaker opoids
(codeine, dextropropoxyphene , tramadol) and then strong Oral route was preferred with a fixed schedule dosing to
opioids ( morphine, methadone, oxycodone, hydromorphone, manage constant pain and prevent pain from worsening.
buprenorphine ) depending on pain intensity. Using this, Rescue (breakthrough) dose was combined with regular fixed
pain control can be achieved in 85% of patients. The use of schedule analgesics to control episodic exacerbation. Baseline
guidelines has been studied in over 30,000 patients, proving pain scores were measured for each patient. For mild to
its usefulness and efficacy ( Zech 1995 ). However, despite moderate pain (VAS ≤ 7) , step 1 analgesic, NSAID, diclofenac
the availability of effective guidelines for pain control, most sodium (50 mg TDS) was prescribed. Pain scores were
cancer patients have a poor quality of life which increases reevaluated after 48 hrs and change of score was recorded.
their agony. Effective pain management improves quality of If pain persisted (same score), worsened (score increased)
life as well as the ability to tolerate diagnostic and therapeutic or score decreased but with a VAS score of > 4 , case was
procedures (Blanchard 1986). Henceforth, this study was considered as non – responder and patient was switched to
done to assess the need of pain management in cancer cervix step 2 analgesic. Step 2 was also applied directly to patients
and to evaluate the efficacy of pain management by WHO presenting with severe pain ( VAS >7) at time of recruitment.
stepladder pattern in the patients of cancer cervix.Drugs used in step 2 was oral Tramadol (50 mg QID ) along
with Diclofenac ( 50 mg TDS) . VAS Score was reevaluated
MATERIAlS AND METHoDSafter 48 hrs. If score still remained above 4; adjuvant analgesics
This pilot prospective cohort study was conducted in the (Amitryptiline 25–75mg OD, Prednisolone 5mg BD – 10 mg/
Department of Obstetrics and Gynaecology, in collaboration day ) were added to step 2. Step 2 non – responders were
with Department of Anaesthesia, KGMU , over a period of treated with step3 protocol. In step 3, tab Morphine (10 mg
one year. Total 209 patients were diagnosed as carcinoma BD upto maximum 30 mg BD) was given after stopping all
cervix, admitted in the Department of Obstetrics and other drugs. After 48 hrs, scores were reevaluated; if scores
Gynaecology were recruited in the study. These patients were remained >4; adjuvant analgesics (Amitryptiline 25–75 mg
either receiving or were planned for chemoradiation. Patients OD, Prednisolone 5mg BD – 10 mg/day) were added. After
with systemic debilitating diseases (renal failure, Diabetes 48 hrs if still pain scores did not decrease to <4, case was
Mellitus, HIV, respiratory and hepatobilliary diseases), declared as failure as per study protocol and some other
peptic ulcer, bleeding diathesis , thrombocytopenia, epilepsy palliative measures (neurolytic sympathetic plexus block,
or history of seizures and patients who underwent major epidural block, epidural neurolysis) was applied to relieve
surgery within 2 weeks were excluded. Written informed pain. Once the patient’s pain score declined to 0; she was
consent was taken from each patient before pain assessment followed up to 2 weeks so as to check any increase in pain.
and management. Demographic details and complete At each step of the ladder, adjuvant drugs (laxatives/stool
history was recorded. General, systemic and gynaecological softeners ,antiemetic) were considered in selected patients to
examination was done. Variables recorded were age, parity, treat concurrent symptoms (Mercadante 2001).
presenting complaints, stage of disease, delay in start of STATISTICAl ToolS
treatment, uterosacral ligament involvement, radiotherapy,
anaemia, smoking/ tobacco, poor family support.Was done using SPSS (Statistical Package for Social Sciences)
version 15.0 statistical analysis software
Initial pain assessment was done by taking detailed pain
history regarding pain characteristics like intensity, location, A total 209 patients of carcinoma cervix were enrolled in the
quality, duration and temporal pattern. Pain intensity was study. The mean age of patients in this study was 49.7 yrs and
measured by visual analogue scale.VAS is a graduated line maximum patients were in the age group 41–50 years (48%).
100 mm in length , anchored by word descriptors at each end Majority of the subjects were multiparous (67.5%), residing
like no pain and worst pain. The patient marks on the line in rural areas (80.3%), of low socioeconomic status (80%) and
the point that they feel, represents their perception of their illiterate (85%) . Most common presenting symptoms were
current state. The VAS score is determined by measuring in discharge per vaginum (75%), pain (61%), postmenopausal
millimeters from the left end of the line to the point that the bleeding ( 44%) , post coital bleeding (15.7%), bladder and
patient marks. According to VAS score pain was categorized rectal symptoms (10%). Most common type of pain was low
into mild, moderate and severe categories. Patients with backache (70%) followed by lower abdominal pain (52%)
mild pain, have VAS scoreEJMR in the range of 1–4, those having and perineal pain (34.6%). Majority of patients had pressure
moderate pain have VAS score, in the range of 5–6 and like continuous aching pain (74%) with the duration of onset
patients having severe pain have VAS score ≥ 7. Subsequent of pain being < 6 month in most of the patients. After pain
assessment was done after giving the drug , at regular intervals assessment of 209 patients, 149 were found eligible for pain
and at each new report of pain. It was done 24–48 hours after management as per WHO step ladder pattern and their
oral administration.response was analysed Out of 149 patients with pain, 44.9 %
(67) patient achieved complete pain relief at step 1. Out of
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the remaining 82 patients , 5 were lost to follow up. 49.3 % and step of pain relief was analysed using chi square test.
(38) achieved complete relief at step 2 , however 5 patients Uterosacral ligament involvement was associated with
also required adjuvant medication along with step 2. Only 39 higher step of pain relief (p<0.0001). In 93% of patients
patients did not reach score of zero after step 2 but 35 (89.7%) with uterosacral involvement, no pain relief was seen at step
out of them achieved complete relief after step 3. Out of 142 1.Other factors like presence of anaemia, addiction, delay in
patients (excluding lost to follow up), 2 cases were declared as start of treatment, post radiotherapy, poor family support ,
failure. Among these failure cases, one of them had metastasis old age , illiteracy , low socioeconomic status were studied
of femur and symphysis pubis; bisphosphonates were started. using logistic regression analysis. These factors did show
Other patient had bladder and bowel involvement diagnosed an increased risk ratio but were not statistically significant.
on repeat cystoscopy.Side effects were observed in all analgesic group of patients,
Association between involvement of uterosacral ligament more commonly with Morphine (30.2%) and Tramadol
Table 1 : Correlation between stage of the disease and severity of pain
StageNo. PainNo Pain mildModerate Severe
124 7 (29.2%) 17(70.8%) 4 2 1
288 57(64.8%) 31(35.2%) 6 42 9
390 78(86.7%) 12(13.3%) 8 29 41
47 7(100%) 0 ( 0%) 0 0 7
Tot a l209 14960 18 73 58
RESPoNDERS 18 72 57
NoN RESPoNDERS 0 1 1
1. Stage Vs Pain: χ
=35.850 (df=3); p<0.001
Table 2 : Correlation between initial pain scores and response to step ladder therapy
StepVA SNo.RespondersNonlost to Response to
11–691 67 (73.6%)24––
2nonresponders of step1 24 16/23 (69.6%) 7/23 (30.4%) 1
2direct + nonresponders of 81 33/81(40.7%) 48/81 (59.3%) ––
2+adjuvants nonresponders of step 2 48 5 39 45/44(11.4%)
3nonresponders of step 2 39 35 (89.7%)4 (10.3%)–
3+adjuvants nonresponders of step 3 4 22–2/4(50%)
Table 3 : Correlation between stage of disease and response to pain , the proportion of responders decreased from stage 1
to stage 4 showing a statistically significant inverse
STAGENUMBER RESPoNDERS NoNRESPoNDERS
(including lost to follow up)
1 7 7 (100%) 0
2 57 57 (100%) 0
3 78 75 (96.1%) 3 ( all 3 lost to follow up)
4 7 3 (42.9%) 4 ( 2 were lost to follow up)
association between stage and response rate ( p< 0.001)
=54.219 (df=3); p<0.001
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Table 4 : Correlation between stage of the disease and step of pain relief
STAGESTEP 1STEP 2STEP 3FAIlED
( n= 67)(n = 38) ( n = 37)( n= 2)
1 ( n= 7)6/7 (85.7%) 1 /7 (14.3%) 00
2 (n=57)43/57 ( 75.4%) 14/57 (24.6%) 00
3 (n=75)18/75 (24 %) 23/75 ( 30.7%) 33/75 (44%) 1/75 (1.3%)
4 (n=5)– 0/5 (0%) 4/5 (80%) 1/5 (20 %)
Table 5 : Shows an inverse association between response rate and initial pain category (p<0.001)
INITIAl PAIN SCoRERESPoNDERSNoN RESPoNDERS
1–4 18 0
5–6 72 1
>=7 52 1 + 5 ( lost to follow up )
=6.824 (df=2); p<0.001
Chi square test ‘p’ value = 0.0001
(25%) compared from Diclofenac, constipation was more step 2 the response rate was only 29.3%, showing a statistically
commonly seen with Morphine (25.6%) compared from significant difference (p<0.001). This indicates that among
Tramadol (8.5%). Epigastric pain was observed only in patients directly recruited for step 2, the protocol does not
Diclofenac group (10.9%). Physical dependence, tolerance seem to be a good–fit. Among patients recruited to step 2,
and addiction was not seen.after failure of step 1, the response rate was 69.6% which was
DISCUSSIoNat par with the response rate at step 1 (73.6%) (p=0.696). This
indicates the appropriateness of protocol. Overall response
Van den Beuken (2007), in a review showed that prevalence among patients recruited to step 2 (both directly recruited
of pain was 50% in all cancer stages, 64% in patients with and those promoted to step 2 after failure of step 1) was 40.7%
metastatic or advanced stage disease, 59% in patients on which is significantly lower as compared to that for step 1
anticancer treatment and 33% in patients after curative (p<0.001). As highlighted above, this difference in response of
treatment. In the present study, 71.3 % patients had pain two steps was owing to low response rate observed amongst
as the presenting complaint and majority of the patients directly recruited subjects of Step 2.
(57%) with pain were in advanced stage (3 and 4) followed
by 38.2 % in stage 2 and 4.6 % in stage 1 of cancer cervix. Response to step 3 (89.7%) was significantly higher as
Thus, incidence of pain increasing with stage of the disease. compared to both steps 1 and 2, thereby indicating its utility
Pain evaluation in the present study was done using Visual as the terminal, final step of the protocol. 40.7 % of severe pain
analogue scale (Wewers 1990). Various other methods of patients responded to Tramadol and 89.7 % of severe pain
pain measurement are Edmonton symptom assessment patients responded to morphine. Thus, Morphine was found
(Bruera 1991), Wisconsin Brief pain inventory (Cleeland to be more effective drug in (p<0.001) for severe pain. Gatti
1994), Memorial pain assessment card (Fishman 1987), A et al (2009) found that with Morphine therapy 30 –60 mg
McGill pain questionnaire (Melzac 1987), Hopkins pain / day VAS score reduced significantly. They concluded that
rating instrument (Grossman 1992), Simple descriptive scale Morphine therapy could be implemented as a standard therapy
(McGrath 1998), Numeric pain distress scale and Facial scale. to manage moderate to severe chronic pain in cancer patients.
The goal of initial assessment of pain is to characterize the Grond S. etal (1999) compared the efficacy and safety of high
pathophysiology of pain and to determine the intensity of dose Tramadol and low dose Morphine for mild to moderate
pain and patients ability to function.cancer pain and observed high dose Tramadol is equally
Ventafridda V etal (1990), in a study found NSAIDs effectiveMorphine. and Wilder safe Smith for mild etalto moderate (1994) observed cancer thatpain foras low strong dose
effective and relatively well tolerated in treatment of cancer pain Morphine is more effective than Tramadol.
cancer pain. McNicol E etal (2004) found that nonsteroidal
anti–inflammatory drugs were preferred for mild to moderate Pain intensity at initial assessment is a significant predictor of
cancer pain. Pain intensity increases with advancing stage response rate in pain management amongst cancer patients.
due to involvement of ureters, pelvic wall or sciatic nerve We observed that as the initial VAS score increased, the
routes. This was confirmedEJMR with findings of this study since response rate decreased (p<0.001). Robin et al (2009) in
the severity of pain increased (p<0.001) with stage of disease.a study found that pain with moderate to severe intensity
Radbruch L etal (1996) found that Tramadol is safe and effective required significantly higher opioid doses and more adjuvant
in the treatment of mild to moderate cancer pain when used in modalities.
combination with non opoids In present study, Step 1 response Guay D R (2001) evaluated the analgesic benefits of tricyclic
rate was 73.6%. However, among patients directly recruited for antidepressants in cancer patients. Wooldridge J E etal (2001)
45 2014 JOURNAL OF MEDICAL RESEARCHVol.1 No.1Vol.1Jul.–Dec. 2014ERA’S JOURNAL OF MEDICAL RESEARCHJul.–Dec. No.1ERA’S
Table 6 : Shows comparison of response at various steps of treatment
Comparison of response to therapy at different stepsP – value
Step 1 vs Direct recruited for Step 2χ
Step 1 vs Non–respondents of Step 1 given Step 2 therapyχ
Step 1 vs Overall Subjects of Step 2 therapyχ
Step 2 vs Adjuvants added to step 2χ
Step 3 vs Step 1χ
Step 3 vs Step 2χ
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