If a Child Vomits After an Oral Medication—Should We Re‐Dose or Not?

ABSTRACT

Vomiting after oral administration of medication is common in children. Despite this, there is a lack of formal guidelines and recommendations on this topic. This article is intended for doctors and nurses who treat children to support the management of this everyday clinical dilemma. This article describes the development of a decision support tool and provides an overview of factors to consider. The decision support tool provides advice for making informed decisions. It was based on a literature search combined with an informal consensus discussion in a group of paediatricians, clinical pharmacologists, and clinical pharmacists, followed by an internal review. The decision support tool is now in clinical use.

1. Introduction

Vomiting after oral administration of a medication is a common clinical problem in children, especially in younger children. There is often uncertainty about the absorption of the given dose and whether to re‐dose or not. There are no guidelines or recommendations from competent authorities or professional associations to support decisions. These situations are typically managed according to the clinician's experience and judgement.

The time between administration of a medication and vomiting is traditionally seen as the most important factor, as demonstrated in a Canadian survey study from 2010 [1]. Most respondents in the survey answered that they would follow a general rule to re‐dose if vomiting occurred within 30 min, and that they would not re‐administer if more than 60 min had passed. In 2022, a similar study was conducted in a Tertiary Care Hospital in India using the same questionnaire. The participants rated the time after administration as the most important factor [2]. At that hospital, there was a consensus that medications should be re‐administered if the patient vomited within 30 min after administration and no dose should be readministered if vomiting occurred more than 60 min after administration. Both studies concluded that, in addition to time, other factors such as drug type, dosage form, and patient status need to be considered [1, 2].

Thus, there is a paucity of written information to support healthcare professionals in making informed decisions in this common clinical dilemma. At the Queen Silvia Children's Hospital, a tertiary paediatric hospital in Gothenburg, Sweden, young doctors and nurses expressed a need for guidance to support clinical decisions about whether to re‐administer or not when a child vomits after taking an oral medicine. We, therefore, set out to establish a clinical routine for these situations and at the same time educate young doctors and nurses to consider additional factors.

2. Methods

The development of our decision support document was undertaken in four steps: (1) identification of clinically relevant substances, (2) literature search and review, (3) paediatric and clinical pharmacologic discussion, and (4) internal review; described below. There are several aspects to consider when assessing the risk–benefit situation for giving a patient an additional dose or no dose after vomiting. It is important to note that each patient and each situation must be assessed individually.

2.1. Identification of Clinically Relevant Substances

Clinicians from various departments at Queen Silvia Children's Hospital (e.g., paediatric cardiology, paediatric neurology, paediatric emergency medicine, and paediatric endocrinology) were asked to list the medications they considered most important in their clinical work and where a decision support tool would be helpful for the situation when a child vomits after a dose of an oral medication. This resulted in the identification of 40 substances which are administered orally (Table S1). The list of identified medicines included a variety of dosage forms, including oral solutions, oral drops, tablets, capsules, granules, and extended‐release tablets.

2.2. Literature Search and Review

We conducted a literature search on PubMed to identify articles on vomiting of orally administered medications using the following keywords: vomiting, paediatric, oral + medication. The literature search could only identify two survey studies relevant to the topic [1, 2]. Neither of these studies added information relevant to the clinical decision to re‐dose or not. In a comprehensive literature search, additional articles on oral drug absorption, gastric emptying, and pharmacokinetics were identified. These articles were used for the paediatric and clinical pharmacologic discussion.

2.3. Paediatric and Clinical Pharmacologic Discussion

We set up a multidisciplinary collaboration between paediatricians, clinical pharmacologists, and clinical pharmacists to develop the decision support document. Two specialists in paediatric medicine (CAG, GL), two specialists in clinical pharmacology (ALE, JMK) and two clinical pharmacists (MD, LD) identified important key factors to be included in the clinical guideline through informal consensus discussions. We compiled pharmacological and pharmaceutical information regarding dosing regimens from local and national sources such as local routines, national treatment recommendations, the Swedish national medication database ePed [3] and the summary of product characteristics (SmPC) for each of the medicines included.

We identified three key areas to consider when deciding whether to re‐dose or not (see below). All three key areas were considered equally important for the clinical decision. The table containing our local recommendations and special considerations for all identified substances is available as a supplement (Table S1). It does not claim to be exhaustive or complete but may be useful to others.

2.3.1. Considerations Regarding the Patient and Medical Condition: Assessing the Risk–Benefit of Re‐Dosing Versus Underdosing

The patient's medical background and present condition are essential information. The treatment regimen, e.g., if the patient received the medication for the first time as a single dose, as needed, or as continuous treatment, should be considered.

A more acute indication gives a greater inclination to re‐dose, compared to a medication administered regularly. In some cases, it is important to maintain adequate treatment effect without interruptions. A narrow therapeutic index or a medication with risk of severe adverse reactions reduces the willingness to re‐dose, and a medication where one missed dose may lead to withdrawal, rebound, or other symptoms increases the motivation to re‐dose. For the clinician, these factors are important information in the risk–benefit consideration for re‐dosing or not re‐dosing. It is important to note that the decision support tool does not give a nurse the right to decide regarding re‐dosing, as the decision to give an additional dose is the physician's responsibility in Sweden.

Monitoring the patient for relevant clinical symptoms, in addition to laboratory findings, may in some cases help to assess if a significant amount of the medicine is likely to have been absorbed. This is easier to assess if relevant clinical parameters, e.g., pain, temperature, pulse or blood pressure, have been monitored continuously. In addition, the present clinical condition of the patient is an important factor when considering whether an additional dose is needed. In uncertain cases, the nature of the substance as well as the reason for the treatment and the patient's situation must be considered. An additional dose of midazolam could be potentially harmful if the child receives a double dose for sedation, but beneficial if it is used to prevent seizures. In contrast, an additional dose of an antibiotic might be less hazardous than not receiving a full dose, especially when treating an acute infection.

Aspects to consider:

• Evaluate the patient's indication for the medication.

• Evaluate the risk–benefit for the patient of receiving no or too low dose, or double dose?

• Evaluate the patient's clinical symptoms and/or laboratory findings to detect if the medicine shows an effect.

2.3.2. Considerations Regarding the Medicine (Substance, Dosage Form, Pharmacokinetics)

The same substance can be found in different oral dosage forms (oral solution, tablets, capsules, granules, or extended‐release preparations). The dosage form is an important aspect to consider. Some medicines have a rapid release and absorption and hence a rapid onset of action. Others, such as extended‐release preparations, have a protective coating and may reach their maximum concentration several hours after a given dose. The only way to be completely certain that the child has not absorbed anything is if the medicine is visible in the vomit in its entirety. The assessment is less certain if the child vomits an oral solution or parts of a tablet.

It is not always possible in the clinical situation to read and consider pharmacokinetic and pharmacodynamic information about a medicine. The recommended frequency of administration can be helpful; to miss one dose of a medication given as multiple daily doses might not affect the patient as much as missing a dose administered once daily. In this case, it could be possible to wait and re‐dose after a while. For medicines with long half‐life at steady‐state, there may be additional factors to consider such as whether steady‐state has been reached and the relation of dosing interval and the medication's half‐life. It is also important to know which drugs have a narrow therapeutic index. These drugs have small differences between therapeutic and toxic doses, and an additional dose could be hazardous for the patient. This decision depends on the situation, the medication, and the patient's condition.

Aspects to consider:

• Have any residues of the medication been observed in the vomit? If yes, try to quantify the amount.

• Does the substance/drug have a narrow therapeutic index?

• How rapidly is the drug released and absorbed?

2.3.3. Considerations Regarding Time Aspects

When a medicine is administered orally, the key physiologic processes here for absorption are gastric emptying and intestinal motility. They are the primary determinants of the rate at which drugs are presented to and dispersed along the mucosal surface of the small intestine [4]. Absorption is also influenced by the drug's physical and chemical properties such as solubility, as well as the type and design of the formulation [5]. Maturation is the key source of variability in children. Differences in maturation as well as different formulations are factors that add to the variability of absorption [6, 7]. The few studies that have evaluated gastric emptying and absorption in children are not conclusive due to differences in study design and heterogeneity of paediatric patients [5, 8]. As a result, absorption and transit through the gastrointestinal tract in children remain poorly understood [9].

Gastric emptying varies greatly between individuals and is influenced by several factors, such as the patient's age, whether the patient is ill or has an underlying medical condition [7, 9, 10, 11]. Other factors of importance for influencing both gastric emptying and absorption include whether the medication is taken on an empty stomach or together with food, the composition of the food, and the body position during the meal [8, 10, 12]. In addition, nausea or critical illness may reduce gastric emptying [11]. It is also known that liquids empty faster than solids [10]. The rest of the absorption processes, once the medicine has left the stomach, are not important for the decision whether to give an additional dose after vomiting. However, if the concentration of a medicine is determined for guidance in the decision whether to give additional medicine or not, it is important to know whether the medicine is absorbed fast or slowly to be able to interpret the measured concentration correctly. The lacking or inconclusive data for children, together with a plethora of factors influencing both gastric emptying and absorption, contribute to the complexity of the assessment.

Traditionally, clinical recommendations are based on the time from oral intake of a medication to the patient's vomiting. Cut‐offs of 15, 30, or 60 min are often used for the clinical decision to re‐dose or not and are also mentioned in the articles by Kendrick et al. and Thangaraju et al. [1, 2]. Despite limited evidence, we decided to use the same cut‐offs in this work as a clinically established reference. If the patient vomits more than 60 min after the medicine was given and no residues are visible in the vomit, we suggest that it is likely that the medicine has passed through the stomach, reducing the risk that vomiting affected the absorption of the medication.

Aspects to consider:

• How much time has passed between medicine intake and vomiting?

• Could monitoring of the concentration of the medication be of benefit?

2.4. Internal Review

Before the document was finalised for clinical use, it was reviewed internally by the clinicians involved in the initial search for relevant medications, as well as by two clinical pharmacists, MD, LD.

2.4.1. Considerations Before Next Oral Administration: Prevent Nausea and Vomiting

We want to emphasise the importance of taking measures to prevent vomiting, where possible.

Children may vomit for several reasons: the taste of the medicine, fear or discomfort, pain or nausea, or anxiety about the situation in which the medicine is given. It is important to know if the patient has experienced problems earlier, e.g., if there are underlying conditions that may cause nausea or vomiting, or if the vomiting represents new symptoms that need evaluation. It can be helpful to optimise the situation and, if possible, create a calm and secure atmosphere to prevent nausea and vomiting. Moreover, it is important to use the correct technique for administration of the medicine. Nurse‐led training for parents on how to administer a medication can be an important intervention to successfully administer a medication to a child. In some situations, if the child refuses to take the medication orally, for example because of bad taste, a change of dosage form, or even a change of substance can be a way forward. This is particularly helpful if the child is not used to taking oral medications and the caregivers are inexperienced in giving oral medications. For older children, it is important to ask about the patient's preference for dosage forms (given current availability of different dosage forms). A change of dosage form or substance may be an option if alternatives are available. Dosage forms other than oral solutions (e.g., tablets, capsules etc.) are less prone to bad taste. There is often a reluctance to prescribe and administer tablets, but Bracken et al. showed that tablets can potentially be acceptable for children as young as 4 years old [13]. If the patient, despite optimal conditions and technique, still has nausea and risk of vomiting, the use of an antiemetic to prevent vomiting should be considered.

Aspects to consider:

• Does the child need an antiemetic before other medications are given?

• Can the medication's dosage form be optimised according to patient preference?

  • ○
    Involve the child in choosing between liquid or solid oral dosage form.
  • ○
    If available, choose medication based on taste preference.
  • ○
    Choose the highest concentration oral solution to minimise volume.
  • ○
    Even younger children may be able to swallow solid oral dosage forms.
  • ○
    Coat the tablet to facilitate swallowing and mask taste.

3. Concluding Remarks

Vomiting after administration of an oral medicine is a common clinical situation in children. It may occur at any age but is seen more often in younger children where oral solutions are more commonly used. Guidelines to support clinical management are lacking. We therefore developed a clinical decision support tool through a multidisciplinary collaboration between paediatricians, clinical pharmacologists, and clinical pharmacists. We suggest considering the patient's situation and medical background, the medication, and its dosage form, and finally the time between administration and vomiting. In addition, we recommend preventive measures to reduce the risk of nausea and vomiting to reduce the need for repeated administration attempts. It is important to assess each patient and situation individually (Figure 1).

FIGURE 1.

Aspects to consider if a child vomits after administration of an oral medication.

If, despite best efforts, the child vomits the medicine, this article will hopefully provide some advice on aspects to consider when deciding whether (or not) to re‐dose. Eventually, it might be necessary to change the dosage form, the route of administration, or the substance.

The main message is to be aware that, in addition to the commonly used time aspect between oral administration and vomiting, other important parameters need to be considered, such as the patient's current condition, medical history and drug properties. This clinical overview aims to provide clinical advice and support clinical decisions in the absence of official guidelines but does not claim to be exhaustive or complete. It has been developed to assist healthcare professionals, especially young professionals with limited experience. Although primarily intended for clinical use at the Queen Silvia Children's Hospital in Gothenburg, Sweden, our decision support tool could potentially be useful in other hospitals as well. We hope that this work will inspire others to add recommendations for other medications as well as information for parents about medicines used at home.

Author Contributions

Christiane A. Garnemark: conceptualization, investigation, writing – original draft, validation. Gustaf Lernfelt: conceptualization, investigation, writing – review and editing, validation. Magnus Dahlander: writing – review and editing, validation. Lisa Diep: validation, writing – review and editing. Anna L. Eriksson: conceptualization, investigation, writing – review and editing, validation. Jenny M. Kindblom: conceptualization, investigation, writing – original draft, validation.

Supporting information

Table S1. List of oral medications identified through discussion with clinicians at the Queen Silvia Children’s hospital with recommendations and comments.