This is a case study of a 26-week pregnant woman, pseudonym Saafia, who required an antiemetic prior to commencing a glucose tolerance test (GTT) in an outpatient setting. A GTT requires the woman to drink a sugary drink to test for gestational diabetes (Royal College of Obstetricians and Gynaecologists (RCOG), 2011). Saafia had attempted a GTT previously but had been unable to complete it as she vomited the drink after ingestion. This article will consider the different prescribing options available to a non-medical midwifery prescriber working in this outpatient setting. The Calgary-Cambridge consultation model was used to assess the patient and to reach a shared prescribing decision. It is part of the Nursing and Midwifery Council (NMC) code that midwives should practise safely by prescribing within the limits of their competency (NMC, 2018) and the NMC has adopted the Royal Pharmaceutical Society (RPS) competency framework (NMC, 2019). It is demonstrated throughout the article how the prescriber demonstrated these competencies in this case.
There are no guidelines, local or national, stating what antiemetic to prescribe in this scenario. It is important to note that many studies consider the safety and effectiveness of antiemetics in early pregnancy (Magee et al, 2002; Mathews et al, 2010; Boelig et al, 2018), however, Saafia was is in her second trimester. These studies will be discussed as there is limited other research and they provide the evidence base upon which guidelines are written.
It is generally accepted practice to prescribe cyclizine in this scenario in the author's local trust, on the advice of the consultant. The rationale for the decision over other antiemetics in the absence of guidelines will be discussed. This case study was originally written by a midwife undertaking a prescribing course. Therefore, while it is based on a real case, it was written to demonstrate the rationale for the prescribing decision and the author's adherence to the RPS competency framework. The situation is therefore hypothetical, and some details from the real patient have been altered.
Consultation model
The Calgary-Cambridge model was chosen to assess this case study because it was the most structured, practical, patient-centred model and it allows a way to close the session when compared to the other models (Denness, 2013). Furthermore, research in Iran has demonstrated that midwifery students trained in the Calgary-Cambridge model have better communication skills and are able to better conduct ‘interviews’ with patients (Baniaghil et al, 2022). This research may not be generalisable to the UK, but it is still an example of how this consultation model is effective in midwifery practice. The model has five stages: initiating the session, gathering information, physical examination, explanation and planning and closing the session. In addition to these stages, there are two overarching themes: ‘provide structure’ and ‘build the relationship’ (Denness, 2013).
‘The first 90 seconds of a consultation is crucial to forming a relationship between patient and practitioner.’
While consultation models allow clinicians to process the information provided to them by the patient, and to communicate, in a structured way (Dennes, 2013), there is very little research into how empowered or disempowered patients feel with the different models (Manalatas et al, 2021), which is something to be mindful of when using these models in practice.
Initiating the session
The first 90 seconds of a consultation is crucial to forming a relationship between patient and practitioner. During the ‘initiation of the session’ stage of the model, it is important to introduce oneself (which is particularly important when the role is new, such as in prescribing), and to listen to the patient's concerns without interrupting them (Munson and Willcox, 2007). Saafia explained that she needed an ‘anti-sickness tablet’ prior to commencing the GTT, because in her previous test she vomited after ingesting the solution. Pregnant women often present asking for an ‘anti-sickness’ tablet as they feel nauseous after already drinking the solution. Given that an antiemetic would not work in these cases, the decision not to prescribe would be just as valid. In this case, it was established that Saafia had not already started the test and therefore an antiemetic could be considered.
Gathering information
The next stage of the model is ‘gathering information’, which involves history taking (Munson and Willcox, 2007). According to the Oxford Medical Education (2021) website taking a history involves: introducing yourself, presenting complaint, history of the presenting complaint, past medical history, drug history, allergies, family history, social history and systems review. It is important to understand the history of the presenting complaint.
Nausea and vomiting in pregnancy affect up to 80% of women with 0.3–3.6% of women developing the most extreme form; hyperemesis gravidarum. In 90% of women, symptoms will abate by 20 weeks (Royal College of Obstetricians and Gynaecologists (RCOG), 2016), which is likely why most studies focus on the early stage of pregnancy. During this time, organogenesis occurs, meaning that the risk of teratogenic effects is greatest (Alwan and Chambers, 2015). The exact aetiology of nausea and vomiting in pregnancy (NVP) is unknown. It is likely to be multifactorial and could be because of hormonal changes, such as an increase in human chorionic gonadotropin (hCG) hormone and oestrogen, reduced gastric motility because of progesterone and delayed gastric emptying seen in pregnancy (National Institute for Health and Care Excellence (NICE), 2021a).
Saafia was a low-risk pregnancy with no other medical history. She was not taking any other medications, had no allergies and had no relevant family or social history. There was also nothing of note on her systems review. Saafia reported that she was infrequently vomiting and had only vomited recently when asked to do a GTT. A formal PUQE score (recommended by the RCOG to grade the severity of nausea and vomiting in pregnancy) was therefore not performed (RCOG, 2016). Nausea and vomiting during pregnancy can only be diagnosed when other differentials are ruled out. These include infections (such as urinary tract, gastrointestinal and pyelonephritis), peptic ulcers, pancreatitis, neurological and metabolic conditions (RCOG, 2016). Saafia was well in herself and did not report any abdominal pain. Therefore, it was not considered necessary to do any observations or a urinalysis for Saafia to be diagnosed with mild nausea and vomiting during pregnancy.
During this stage, the prescriber attempted to show empathy when discussing Saafia's symptoms with her by asking about her vomiting and the effect it has had on her mental wellbeing. This is important as many women with nausea and vomiting feel dismissed by health professionals (Locock et al, 2008). Showing empathy helped build a relationship with Saafia, which is an important part of the consultation model (Dennes, 2013).
Physical examination
The next stage of the consultation model is ‘physical examination’ (Denness, 2013). Given Saafia had no abdominal pain and her vomiting had settled when not required to do a GTT, it was the midwife prescriber's clinical judgement that a medical review (and therefore an abdominal examination) was unnecessary. Therefore, this stage of the consultation model was not performed. Dennes (2013) advocates for clinicians to not follow the model rigidly, to allow for one's own personality and empathy, and to suit the needs of the consultation. Research has shown that this is often the case, with clinicians going back and forth through the phases (Manalastas et al, 2021). By assessing the patient to rule out any differentials in order to come to a diagnosis, the midwife in this case study was adhering to the first step (assessing the patient) in the RPS (2016) competency framework.
Explanation and planning
The next stage of the consultation model is ‘explanation and planning’. Saafia is of Pakistani origin, which is a risk factor for gestational diabetes (NICE, 2015). Undiagnosed gestational diabetes can lead to large for gestational age babies, stillbirth and shoulder dystocia (RCOG, 2011). Given that the test was attempted previously and was unsuccessful because of her vomiting, it is reasonable to decide to prescribe an antiemetic, given the consequences of undiagnosed gestational diabetes.
According to local trust guidelines midwives are allowed to prescribe the following antiemetics: cyclizine, metoclopramide, ondansetron, prochlorperazine and promethazine. Therefore, the midwife prescriber in this scenario would need to choose one of these antiemetics to adhere to trust policy. There are no national or local guidelines on what antiemetics to prescribe before a GTT in this stage of pregnancy. In the absence of guidelines, it is generally accepted practice to prescribe one standard dose of cyclizine (50 mg tablet) in the antenatal clinic if a woman requires it for a GTT. This is on the advice of the consultant. NICE (2021b) have produced a table of the advantages and disadvantages of the different antiemetics for use in pregnancy. It is worth noting that unfortunately, the link to the evidence behind these guidelines was not working at the time of writing and therefore an independent assessment of the research could not be performed). This table states that while cyclizine has been accepted practice for many years, like all antiemetics on the non-medical prescribing formulary for the trust, it does not have a license for use in pregnancy. There are no randomised controlled trials (RCTs) for cyclizine on its own to demonstrate its effectiveness. If given near to term, it may cause jitteriness and irritability in the newborn (NICE, 2021b). However, Saafia is 26 weeks pregnant and therefore this is not relevant. Whilst no drug can be said to be 100% safe in pregnancy (Joint Formulary Committee, 2020), there is no evidence to suggest that it is an unsafe drug (NICE, 2021b).
The RCOG (2016) advise cyclizine, promethazine and prochlorperazine as first line, and ondansetron and metoclopramide as second line in the treatment of nausea and vomiting in pregnancy. This is because of the safety profile of the drugs (RCOG, 2016). Cyclizine and promethazine are antihistamines, which are one of the oldest antiemetic drugs given during pregnancy (Gill and Einarson, 2007). A meta-analysis performed on 24 studies, which included 200 000 pregnancies between 1960–1991, showed that pregnancies exposed to antihistamines in the first trimester showed a slightly lower incidence of abnormalities (Magee et al, 2002). A more recent systematic review of cyclizine use in the first trimester found no increased risk of adverse outcomes or fetal abnormalities in women taking antihistamines in the first trimester (Etwel et al, 2017).
Prochlorperazine is a phenothiazine and is also advised as a first line antiemetic by the RCOG (2016). However, the local trust guidelines state that this is second line (Local trust guidelines). The manufacturers advise that some patients treated with phenothiazines for psychotic disorders have developed a glucose intolerance (Electronic Medicines Compendium (EMC), 2020). Therefore, in the absence of any evidence to suggest its superiority as an antiemetic in NVP (Mathews et al, 2015; Boelig et al, 2016; O'Donnell et al, 2016), it is reasonable not to give prochlorperazine as a first line therapy for a test for diabetes. Extrapyramidal effects have been noted in young people taking metoclopramide and there is limited data on the safety of ondansetron which is why these are advised to be second line (RCOG, 2016). Given Saafia had not yet been prescribed an antiemetic, there is no justification to go straight to second line therapies.
While there are no local guidelines for this scenario, there are local guidelines on the ‘management of women with nausea and vomiting in early pregnancy’ (Local trust guidelines). These state that promethazine should be given as a first-line antiemetic, followed by prochlorperazine and metoclopramide as second and third line respectively. The RCOG states that ‘clinicians should use antiemetics with which they are familiar and should use drugs from different classes if the first drug is not effective’ (RCOG, 2016). Both promethazine and cyclizine are antihistamines and therefore the local guideline states that cyclizine should only be given after first, second, and third line medications are ineffective (Local trust guidelines, 2014). While the local guideline does not explicitly state why promethazine was chosen over cyclizine, one would suspect that it is because of the associated cost. While the cost for the oral tablet of cyclizine and promethazine are similar, many women with severe hyperemesis may need to be given the antiemetic via another route, such as intramuscular (IM) or intravenous (IV). Cyclizine solution for injection ampoules are at least double the cost of promethazine ampoules (Joint Formulary Committee, 2020, 2020). Cyclizine has a limited sedative effect (EMC, 2018), which contrasts with promethazine (Joint Formulary Committee, 2020). Since the cost of the oral tablets are similar, cyclizine could be considered a better choice given the sedative effect in this scenario.
It is important to consider the available evidence, however limited, to adhere to the second RPS (2016) competency framework which is ‘identifying evidence-based treatment options available for clinical decision making’. A systematic review of treatments for nausea and vomiting in pregnancy by O'Donnell et al (2016) found that the data are very limited, with the overall quality of evidence being very poor. This review found that antihistamines did appear to have a beneficial effect compared with a placebo in mild symptoms but because of the heterogeneity of the studies, often meta-analyses cannot be performed (O'Donnell et al, 2016). Other studies have found similar heterogeneity (Magee et al, 2002; Mathews et al, 2010), and more evidence is required to demonstrate true efficacy (Koren, 2017).
It is difficult to assess the safety and efficacy of medications used in pregnancy, as RCTs, (the gold standard for research), are often not able to be carried out for ethical reasons (Koren, 2017). Furthermore, as the incidence of congenital malformation is very low, large numbers are required to assess for any teratogenic effects. Therefore, in pregnancy, cohort and case-control studies are often performed. These carry with them a higher risk of bias due to confounding factors (Koren, 2017). Systematic reviews have concluded that there is not enough evidence to advise one antiemetic over another (Mathews et al, 2015; Boelig et al, 2016; O'Donnell et al, 2016). When researching for this case study no research could be found comparing the different antihistamines. This being the case the decision to advise cyclizine by the consultant in this scenario appears reasonable, given that is less sedative than promethazine (Joint Formularies Committee, 2020).
None of the drugs advised by the RCOG have a license for use in the treatment of nausea and vomiting in pregnancy and manufacturers advise avoiding them (NICE, 2019). According to NICE (2019), who have contacted the Medicines and Healthcare products Regulatory Agency, as these drugs are not contraindicated in pregnancy, prescribing them is not considered to be off-label. Since the RCOG guidelines were released in 2016, doxylamine and pyridoxine have been licensed for use in pregnancy to treat nausea and vomiting, which is the only drug to be given this license (NICE, 2019). NICE (2019) acknowledge that some women may prefer taking this medication compared to the other more established antiemetics due to its licence. Given that this drug is not yet in the guidelines and is not a permitted drug that the local trust allows midwives to prescribe, this was not an option at the time for the midwife prescriber in this case at this present time.
It was important to explain to Saafia the importance of the GTT and that there is no evidence to state which antiemetic is better (Mathews et al, 2015; Boelig et al, 2016). Saafia should understand that whilst it is not possible to say that any medication is 100% safe or effective in pregnancy (BNF, 2021), there is no evidence to suggest that it is unsafe (Magee et al, 2002; RCOG, 2016; Koren, 2017; NICE, 2021a). Saafia should be involved in the decision-making for the prescriber to achieve the third RPS (2016) competency, which states that prescribers should ‘present options and reach a shared decision’.
Following a discussion with Saafia, it was decided that the antiemetic that would be prescribed was a cyclizine 50 mg oral tablet to be administered as one stat dose. It can be given IM or IV but as Saafia was tolerating oral foods at the time, an oral tablet was deemed less invasive and more appropriate. She was not taking any medications, did not have any allergies and did not have any health concerns that are cautioned against, (such as epilepsy and severe heart failure), in the BNF (Joint Formularies Committee, 2020). While this case study has established that cyclizine is a reasonable medication to prescribe in pregnancy, it is important to state that it is an appropriate drug to prescribe to Saafia as an individual. Prescribers must understand the dose, side effects and cautions for any drug to be prescribed as outlined in competency 4, ‘prescribe’ in the RPS (2016) framework.
Cyclizine is an H1 antagonist, which is well absorbed from the gastrointestinal tract. It starts to have an effect after approximately 30 minutes, with peak plasma concentrations occurring 1–2 hours following ingestion, with effects lasting for 4–6 hours (EMC, 2018). Therefore, Saafia was told to wait at least 30 minutes after taking the medication before drinking the glucose solution. This waiting time is even more imperative in pregnancy because of the increased gastric emptying time in pregnancy (NICE, 2021a). Cyclizine is metabolised into nor-cyclizine which has limited antihistamine effects. It has a half life of 20 hours and after 24 hours less than 1% of the 50 mg of cyclizine is present in the urine (EMC, 2018).
The exact pharmacodynamics of cyclizine are unknown (EMC, 2018), although there are some theories. The vomiting centre is located within the central medulla of the brain, which sends signals via the vagus nerve and spinal motor neurons to the abdominal muscles, inducing vomiting. H1 receptors and muscarinic receptors are found in the vomiting centre. Cyclizine is an antagonist of the H1 receptors, thereby preventing nausea and vomiting (Bhakta and Goel, 2017). Muscarinic receptors are also found in the vomiting centre and cyclizine is also thought to be a receptor antagonist of these receptors which are thought to contribute to its antiemetic properties (Zhong et al, 2021). In addition, vestibular hyperactivity has been shown in mice to trigger the histaminergic neurones, leading to a release of histamines and vomiting in motion sickness (Zhong et al, 2021), therefore cyclizine may also exert its effect by blocking the release of this histamine. As discussed, the exact aetiology of nausea and vomiting in pregnancy is unknown (NICE, 2021a). Similarly, the effect of cyclizine is uncertain. Therefore, exactly how cyclizine exerts its effects on NVP is not understood.
Closing the session
The final part Calgary-Cambridge consultation model is ‘closing the session’. This stage is important for the patient to discuss any issues they may have but is often omitted by clinicians (Manalastas et al, 2021). Saafia was advised to inform staff if she suffered any adverse reactions to the drug or if it was not effective. This stage is important to ensure that the prescriber meets competency 5 of the RPS (2016) framework, ‘providing information’ and competency 6, ‘monitoring and review’.
Conclusion
This case study highlights the difficulties surrounding research, and the complexities of prescribing, in the pregnant people. Given the ethical difficulties of obtaining good quality RCTs, most antiemetics are advised against by manufacturers in pregnancy (NICE, 2021b). As with most healthcare decisions, the decision to prescribe is about the balance of risk (BNF, 2021). In this case study, the risk of undiagnosed gestational diabetes was considered to be more harmful to Saafia and her baby than a stat dose of cyclizine.
This case study has demonstrates that the midwife achieved RPS competencies 1–6 of the first domain, the consultation. The governance domain includes competencies 7–10. Competencies 7 and 8 are to ‘prescribe safely’ and to ‘prescribe professionally’ respectively. Part of this means only prescribing within the remits of one's professional role and adhering to local and regulatory frameworks, along with issues regarding off label medicines (RPS, 2016), which have been discussed in this article. Competencies 9 and 10 are to ‘improve prescribing practise’ and to ‘prescribe as part of a team’ respectively (RPS, 2016). It is important that non-medical prescribers keep up to date with research, especially in an area of practice such as midwifery, where medications are often advised against. Furthermore, a regular audit of prescriptions should be performed to ensure ongoing competence.
Upon reflection, it could be argued that it would have been appropriate to perform a full set of observations on Saafia and an abdominal palpation. However, given that she was generally well, and taking into consideration the pressures on the unit, it was assessed by the prescriber that this would have been an unnecessary and time-consuming intervention. There was no indication that any of her observations would have been abnormal, and it was established that the only indication to prescribe the antiemetic was for the purpose of the GTT.