Oncology nursing

An audit of chemotherapy-induced nausea and vomiting in children

Frieda Clinton and colleagues present a study at one children's cancer centre into the use and effectiveness of anti-emetics for patients receiving chemotherapy
Correspondence frieda.clinton@olchc.ie Frieda Clinton is an advanced nurse practitioner, haematology oncology unit. Our Lady's Children's Hospital, Dublin, Ireland Maura Dowling is lecturer, school of nursing and midwifery. National University of Ireland, Galway, Ireland Michael Capra is consultant paediatric oncologist. Our Lady's Children's Hospital, Dublin Date of acceptance

Abstract
An audit v(/as conducted of the management of chemotherapy-induced nausea and vomiting in children and young people in the national Irish paediatric cancer unit. Over three months, the anti-emetic medication and the incidence of nausea and vomiting in 50 consecutive patient episodes were recorded among 25 children receiving chemotherapy for diverse malignancies. Anti-emetic prescription was found to be unrelated to the emetogenic potential of the chemotherapy received, so that effectiveness varied. Dexamethasone was used in only one case. Twenty children did not take any anti-emetics following discharge, although 11 experienced delayed vomiting, evidence-based guidelines were established and now include anti-emetic prescription that is proportional to the emetogenic potential of the chemotherapeutic regimen. It is also recommended that staff, patients, families and carers should receive education about the need for prescription and use of anti-emetics after discharge.

May 9 2012
Peer review This article has been subject to open peer review and has been checked using antiplagiarism software Author guidelines www.nursingchildrenand youngpeople.co.uk

effects (Coates ef al 1983). The distress can affect the person's normal activities and quaUty of Ufe significantly (McRonald and Fleisher 2005, Robinson and Carr 2007). People receiving chemotherapy are not at equal risk for developing CINV. Individual characteristics and chemotherapeutic agents are among the factors affecting risk, and the latter are probably the most significant (Anti-emec Subcommittee of the Multinational Association of Supportive Care in Cancer (ASMASCC) 2006, Bloechl-Daum et al 2006). Variation in the management of CINV in children exists nationally and internationally. The aim of this article is to present findings from an audit undertaken at the national Irish paediatric cancer centre of the use and effectiveness of anti-emetics, and the resulting change in the management of CINV.

Background
Nausea, vomiting and retching must be clearly defined for accurate assessment as separate concepts (Molassios et al 2006, Robinson and Carr 2007). Nausea is a subjective, non-observable experience of unpleasant sensations often associated with a feeUng that vomiting is imminent, and can be accompanied by autonomie nervous system activity such as pupu dilation, sweating and saUvation (Morrow ef al 2002, Robinson and Carr 2007). Retching is an attempt to vomit without bringing up anything, is distressing and can be described as 'heaves' or 'gagging'. Vomiting is the forceful expulsion of the contents of the stomach through the oral or nasal cavity. Retching and vomiting are obvious and can be objectively measured (Rhodes and McDaniel 2001, Morrow ef al 2002). CINV is classified into three categories: acute onset, occurring within 24 hours of the initial administration NURSING CHILDREN AND YOUNG PEOPLE

Keywords Anti-emetics, chemotherapy-induced nausea and vomiting, oncology, paediatric nursing

CHEMOTHERAPY-INDUCED NAUSEA and vomiting (CINV) can be a major problem for children with cancer. Children are especially vulnerable to electrolyte imbalance, dehydration and weight loss, and poor nutrition may affect their tolerance of additional chemotherapy. The experience of vomiting creates physiccil and emotional distress for chQd and family or carers: as early as 1983 it was shown that, for patients, treatment-related nausea and vomiting were among the most dreaded adverse September 2012 | Volume 24 | Number 7

of chemotherapy; delayed onset, occurring 48 hours to five days after initial treatment; and anticipatory nausea and vomiting observed among people whose emetic episodes are triggered by taste, odours, sights, thoughts or anxiety secondary to a history of poor response to anti-emetic agents (Fromer 2005, Robinson and Carr 2007, Hesketh 2008). The mechanisms behind acute CINV differ from those behind the delayed or anticipatory forms, the mechanisms associated with various chemotherapy agents may differ, and the schedule or dose of one drug may be affected by another. Combining chemotherapy with radiotherapy or biotherapy may further influence the profile of a person's nausea and vomiting (ASMASCC 2006). /kmong anti-emetics, the 5HT3 receptor antagonists are generaUy more effective than metoclopramide or phenothiazines and are best combined with dexamethasone (the latter may, however, reduce the effectiveness of the chemotherapy) (Zhang et al 2006, PhiUips era/2011). There are few studies and guidelines on the prevention and management of CINV in children cind the national paediatric cancer unit in Ireland identified a need to audit evidence base and practice. This unit is a centralised centre providing care in conjunction with 16 shared-care centres across the country. Provision is for aU diagnosed with cancer under the age of 16 years in Ireland, and this amounts to approximately 160 cases annuaUy.

Aim and objectives

The audit was undertaken to document the management of CINV in children and young people in an attempt to revise and aUgn practice to existing guideUnes (Jordan et al 2011). The main objective was to document the prescribing and administration of anti-emetic therapy, with a secondary objective being to collect data on the effectiveness, where possible, of the anti-emetic medication being used.

Method
The audit took place over three months from August to October 2008, in the haematology/oncology ward of Our Lady's Children's Hospital, Dublin. It was Umited to inpatients for ease of timed accessibity to children and their famiUes, and so that the children and famiUes could acquciint themselves with the assessment tools. An episode was defined as a single admission for chemotherapy administration, and 50 consecutive episodes were recorded. For inclusion in the audit the child had to be aged at least four years to use the tool to assess nausea.
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A prospective design was used, with each episode involving interviewing the chud daily from admission to discharge to assess the degrees of nausea and vomiting experienced. Anti-emetic medication and chemotherapy received were documented each day. On the day following discharge, telephone contact assessed nausea intensity and vomiting frequency, and recorded anti-emetic medication used at home. Prescription was exclusively by the ward staff who were all aware of the audit process. The emetogenic potential of each chemotherapy agent was classified, retrospectively, as low, moderate, high or very high (Table 1, page 20) (Dupuis et al 2008). Chemotherapeutic agents are usually combined, and the agent with the highest emetogenicity directed the appropriate anti-emetic prescription that was required. Nausea and vomiting experienced were assessed by the Pdiatrie Nausea Assessment Tool (PeNAT) (Dupuis ef al 2006) and the MASCC Anti-emesis Tool (MAT) (Molassiotis 2008). The PeNAT, which measures nausea using four facial expression scales, has moderate construct and convergent validity scores (Baxter ef al 2011). First, the family's famiUar terms for nausea and vomiting are elicited. Then, if the child aged four to eight years states they have 'no nausea', faces 1 and 2 are shown. If the child says 'some nausea', faces 3 and 4 are shown and the chud is asked: 'Which face is more Uke you now?' Older children are shown which face means no nausea, or a Uttie nausea, or more nausea and/or a lot of nausea, and are asked: 'Which face is more Uke you now?' On discharge, use of the tool at home was demonstrated to the family or carers. The MAT is a validated eight-item scale that assesses acute and delayed nausea and vomiting (Wood et al 2011). This tool records occurrence (four subscales), duration (two subscales) and frequency (two subscales) of nausea and helps identify patients who are not being appropriately treated with anti-emetic therapy (Molassiotis ef al 2008, Yamaguchi ef al 2009). In a review of patient self-report tools for CINV (Brearley ef al 2008), the MAT'S strengths were highlighted as conciseness and abiUty to be administered at the end of a two- or three-week treatment cycle. The patient or carer was asked to record using the tool as directed, 24 hours following the administration of chemotherapy (for acute emesis) and up to two days foUowing completion of chemotherapy (for delayed emesis). Intensity of vomiting was defined according to the Common Toxicity Criteria (National Comprehensive Cancer Network (NCCN) 2008), as shown in Table 2, page 21.
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Oncology nursing
Ethiccil considerations Although this was not research, informed consent was obtained from the parents/guardians of aU patients and, where appropriate, assent from the children was obtained. Approval from the ethics committee of Our Lady's Children's Hospital was granted. (Table 4, page 22) Vomiting increased a little from days one to five of chemotherapy administration in spite of medication (Table 2), but most children reported no or only 'a little nausea' (PeNAT 1 or 2); three reported more or a lot of nausea (PeNAT 3 or 4) (Table 5, page 22). Anticipatory vomiting occurred in two episodes, acute vomiting in 17 and delayed vomiting in 24. Of the 20 children who did not take any antiemecs after discharge, 11 were not prescribed any on discharge.

Audit results
Table 3 shows that 50 inpatient episodes involving 25 children were recorded (ten girls and 15 boys) with varied malignancies. Days in hospital ranged from one to ten. Most patients in this audit received a combination of a 5HTj antagonist and metoclopramide; and one received dexamethasone. There was no perceived correlation between the an-emec prescribed and emetogenic potential of chemotherapy received:
^ ^ ^ ^ 1 Emetogenic classification of chemotherapy agents
Very high (>90%) Carmustine >250mg/m2 Cisplatin >50mg/m2* Cydophosphamide >l,500mg/m2 Dacarbazine High (60-90%) Carboplatin* Carmustine <250mg/m^ Cisplatin <0mg/m2* Cydophosphamide >750-l,500mg/m2* Cytarabine >l,000mg/m2 Dactinomycin Daunorubicin >60mg/m2 Doxorubicin > 6 0 m ^ m 2 Methotrexate > 1,000mg/m2 Procarbazine Topotecan

Discussion
This was the first audit to be undertaken in the centre to assess children's nausea and vomiting following chemotherapy and an-emetic medication. Inconsistencies in prescribing to manage CINV

Moderate (30-60%) Amsacrine Busulfan Cydophosphamide <750mg/m2 Cydophosphamide: oral

Low (10-30%) Docetaxel Etoposide <60mg/m2 Fludarabine: oral Fluorouracil

Cytarabine > 100-1,OOOmg/m^ Daunorubicin <60mg/m2 Doxorubicin <60mg/m2 Epirubicin <90mg/m2 Etoposide >60mg/m2 Etoposide: oral Idarubicin Ifosfamide Imatinib Irinotecan Methotrexate 250-l,000mg/m2 Mitoxantrone <15mg/m^ Temozolomide Vinorelbine: oral

Gemcitabane Melphalan Methotrexate 51-249mg/m^ Paditaxel Thiotepa Vindesine

Associated with delayed/prolonged nausea and vomiting (Adapted from Dupuis ei ai 2008)

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1 Common toxicity criteria Grade Vomiting None One episode in 24 hours Intravenous (IV) fluids indicated < 2 4 hours Two to five episodes in 24 hours More than six episodes in 24 hours IV fluids or total parenteral nutrition (TPN) indicated > 2 4 hours Life-threatening Requiring TPN or intensive care unit Common toxicity criteria grade

Table 3

Characteristics of patients included in the audit (n=25) Number

0 1

Characteristic Total sample Girls Boys Age range: 4-8 years 8.1-12 years 12.1-16 years > 1 6 years Cancer diagnosis Central nervous system tumour Osteogenic sarcoma Ewing's sarcoma Leukaemia Rhabdomyosarcoma Non-Hodgkin's lymphoma Neuroblastoma Wilms' tumour Pleuropulmonary blastoma Optic glioma Relapsed acute lymphoblastic/ lymphocytic leukaemia Acute myeloid leukaemia Hodgkin's lymphoma inpatient chemotherapy days per episode (n=50) One day Two days Three days Four days Five days >five days

25 10 15

2 3

8 7 8 2

Day 1 2 3 4 5

0 72%

1 14%

2 14% 25%

3 0% 3.1% 11% 0% 0%

4 0% 0% 0% 0% 0%

4 3 3 3 2 2 2 1 1 1 1 1 1

(National Comprehensive Cancer Network 2008)

were evident. The emetogenic potential of the chemotherapy administered was not taken into account and dexamethasone was prescribed for only one patient, despite evidence indicating that it should be an integral component of almost all anti-emec regimens (Kris et al 2006). Factors that favour the use of dexamethasone are: proven benefit in cUnical trials, widespread avaUabiUty in oral form, low cost and incremental effectiveness in people receiving chemotherapies of a high emetic risk. Reported adverse effects, such as a protection of tumour growth, avascular necrosis and suppression of the immune system may be influencing prescribing unduly (Antonarakis et al 2004, Zhang et al 2006). The benefits of dexamethasone are internationally recognised and should be considered carefully in the development of much needed formal, clear and comprehensive guidelines. The PeNAT scale was relatively easy to manage, but children aged less than eight years could only describe how they felt at the moment rather than retrospectively over the previous 24 hours; and the PeNAT scale has not been validated for retrospective nausea assessment and may give
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16 17 5 3 5 4

inaccurate results. The MAT was also easy to understand and use, with sufficient space for the parents or carers to write in the number of vomits as instructed. The anticipatory vomiting documented in two episodes is comparable with other studies. Anticipatory nausea and vomiting, Uke delayed CINV, appear linked to poor emetic control during previous chemotherapy treatments resulting in classical conditioning. The American Society for CUnical Oncology and the National Comprehensive Cancer Network (NCCN) guidelines suggest non-pharmacological interventions for anticipatory vomiting, such as relaxation, systematic
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Oncology nursing
Anti-emetics prescribed in each common toxicity criteria group, as an inpatient and on discharge

Common toxicity criteria Inpatient prescription

Very high Ondansetron Metoclopramide

High

Moderate Ondansetron Metoclopramide Promethazine

Low
Ondansetron Metoclopramide Domperidone

Ondansetron Metoclopramide Promethazine Cyclizine Lorazepam Dexamethasone Ondansetron Metoclopramide Promethazine ; Cyclizine

Prescription on discharge

Ondansetron Metoclopramide

Ondansetron Metoclopramide Promethazine

Ondansetron

desensitisation, hypnosis, guided imagery, music therapy, acupuncture or acupressure (Kris et al 2006, NCCN 2008). Acute CINV manifested in 17 episodes, supporting a study by Holdsworth et al (2006) which showed that complete control of nausea and vomiting was more likely in children from birth to the age of three years than in older children. In the audit reported here, for moderately emetogenic regimens, symptoms were then controlled weD. Delayed CINV is more commonly associated with the use of cisplatin, carboplatLn and/or cyclophosphamide (as weU as vomiting during the acute phase), as was .the case in seven of the
Number of children with Paediatric Nausea Assessment Tool scores 1-4 on days 1-5 ! Face 1 : No nausea i Face 2: A little bit nauseous I Face 3: Feel even more nauseous Face 4: A lot of nausea

children in this study (Dupuis and Nathan 2003). Age and gender had no significant effect on delayed vomiting. However, the relatively high incidence with 11 children experiencing delayed vomiting is of concern, specifically when considering that 24 children did not take anti-emecs following discharge. This may be related to underestimation of risk after being discharged, and/or failure of the medical and/or nursing teams to inform children and parents or carers adequately. Importantly, 11 children did not have a prescription for anemecs on dischcirge, which may have increased the incidence of delayed vomiting in this study. Mertens et al (2003) concluded that delayed emesis may be less efficiently prevented and controlled because it is not as dramatic as acute emesis and medication can be less effective. All members of the multidiscipUnary teams and families should receive education about the need for prescription and use of anti-emetics after discharge. Limitations The sample in this study was small and results shculd be interpreted with caution. Clinical audit has many limitations (Johnston et al 2000). Specific issues with this audit included the tools used: children younger than eight years could not provide retrospective decisions on their nausea in the previous 24 hours, and nausea was also difficult to assess when the child had been discharged from hospital in spite of use of the PeNAT scale at home. Data related to dietary intake and degree of nausea were not obtained in this study and only one of the MASCC diaries given to parents/carers on the first day of their child's admission for chemotherapy was completed.

1
Day
Score 1

3 Number Df children Score 2 Score 3

Score 4

1 2 3 4 5

36 26 33 32 39

8 15 11 15 10

5 8 3 3 1

1 1 3 0 0

Implications for practice

This audit showed the disparity in the management of CINV in the unit in 2008, relative to available
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(PeNAT tool adapted from Dupuis ei ai 2006 with permission)

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international pubUshed guideUnes, and thus contributed to a change of practice. New institutional anti-emetic guideUnes have been introduced, based on those already highlighted in this article, guiding the medical team in the management of CINV, providing consistency and standardising appropriate and-emetic prescribing. In the imit, anti-emetics are now prescribed and administered early in chemotherapeutic treatment, according to the most emetogenic agent being administered. The xmit's postaudit guidelines also address the child's history of anticipatory, acute or delayed vomiting on previous chemotherapy cycles and any antiemetic treatment. Feedback from the child and parents/carers is continuously important in trying to improve their overall care and experience. Plans are currently imder way to re-audit the

management of CINV now that the new guideUnes are estabUshed, and further education of children, parents and carers about new anti-emec regimens is envisaged.

Conclusion
It is important to audit cUnical support of children undergoing chemotherapy and therefore to foUow a consistent, evidence-based, flexible and up-to-date approach in every case. As a result of this study, evidence-based guideUnes have been estabUshed at the U-ish paediatric cancer unit. These include timely anti-emec prescripon that is proporonal to the emetogenic potenal of each individual chemotherapeuc regimen. Informaon and educaon about eatment should always be offered to families, carers and children.

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Conflict of interest None declared Acknowledgement The authors acknowledge the invaluable collaboration of the entire multidisciplinary haematology oncology team at Our Lady's Children's Hospital, Dublin

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