DÄ internationalArchive38/2012Medication Errors in Pediatric Emergencies

Review article

Medication Errors in Pediatric Emergencies

A Systematic Analysis

Dtsch Arztebl Int 2012; 109(38): 609-16. DOI: 10.3238/arztebl.2012.0609

Kaufmann, J; Laschat, M; Wappler, F

Background: Errors in drug administration are among the commonest medical errors. Children are particularly at risk for such errors because of the need to calculate doses individually. Doses that are ten times the correct amount (1000% of the correct dose) are occasionally given and can be life-threatening. In a simulated resuscitation in a pediatric emergency room, an error of this type occurred for one of the 32 medications that were ordered. The highest error rates are to be expected in prehospital emergency medicine. In this review, we analyze the process of ordering medications and describe the potential interventions for lowering error rates that have been evaluated to date.

Method: Systematic literature review

Results: We found 32 original publications that concerned the evaluation of interventions for lowering error rates in the ordering of medications for children. Error rates can be lowered by interventions that improve prescribers’ knowledge of pediatric pharmacotherapy (courses, immediately accessible sources of information) and by aids to the cognitive process of ordering medication (calculators, computer programs, tables of doses by weight). They can also be lowered by raising awareness of the problem of erroneous medication ordering and by monitoring medication orders, as well as by structured communication and standardized, unambiguously labeled drug preparations. In the hospital setting, computer programs for medication orders with a built-in pediatric pharmacological database are highly recommended. In the prehospital setting, the “pediatric emergency ruler” enables accurate estimation of the patient’s weight, provides age-appropriate dosage recommendations, and directly indicates the steps needed for calculation of the correct dose.

Conclusion: Children in medical emergency situations are at significant risk for medication errors. The measures described here can markedly lower the rate of dangerous errors.

LNSLNS
The German pediatric emergency ruler (PädNFL), placed with one end by the heels of a child lying with legs outstretched. Weight, age-appropriate normal values, sizes of equipment, and weight-related doses of emergency drugs can be read off the section that lies by the child’s head
The German pediatric emergency ruler (PädNFL), placed with one end by the heels of a child lying with legs outstretched. Weight, age-appropriate normal values, sizes of equipment, and weight-related doses of emergency drugs can be read off the section that lies by the child’s head
Figure 1
The German pediatric emergency ruler (PädNFL), placed with one end by the heels of a child lying with legs outstretched. Weight, age-appropriate normal values, sizes of equipment, and weight-related doses of emergency drugs can be read off the section that lies by the child’s head

The American Institute of Medicine estimates that 7000 people die every year in the USA as a result of medication errors, including self-medication and doctors’ prescriptions in patients of all ages (1). In hospitals, drug administration errors are also some of the most common medical errors (e1). Because of age group–specific contraindications and the need for personalized dose calculation, children can be expected to be particularly at risk of medication errors (e2e4). For example, in one pediatric hospital the observed rate of potentially dangerous prescribing errors was three times higher (e5) than the rate observed in an identically designed study in adults (e6). The error rate increases in any care situation that requires speed and large numbers of prescriptions (e7). As part of a risk audit in a pediatric emergency department, a tenfold deviation, corresponding to 1000% of the recommended dose, was observed in one in every 766 prescriptions on average, although measures to improve this had already been put in place (electronic prescription system, standardized drug preparation) (2). In a prospective study, as many as one in every 32 prescriptions in a pediatric emergency department contained a tenfold error during simulated resuscitation by pediatric emergency physicians (3). It is important to remember that errors of this scale can cause serious harm and in many cases even prove fatal (4, e8, e9).

Because neither exclusively pediatric staff nor treatment procedures optimized for pediatric patients can be provided for the prehospital emergency care of children (e10), a particularly high error rate is to be expected in this field (e11). A retrospective analysis of 360 prehospital prescriptions in the USA showed medication errors in 35% of all cases. Excessively high doses of intravenous epinephrine were an average of 808% of the recommended dose (5). No specific incidence rates from larger populations are available for emergency medicine (e12), but it is likely that a considerable number of prehospital medication errors are not reported (e13). This means that the likely frequency and the consequences of medication errors in prehospital pediatric emergency care give rise to a substantial danger, which must be reduced.

Method

This article is based on a systematic review of the literature, using a search of PubMed (Table 1).

PubMed research (database existing since 1963, last accessed in May 2012)
PubMed research (database existing since 1963, last accessed in May 2012)
Table 1
PubMed research (database existing since 1963, last accessed in May 2012)

Results

The authors identified 22 clinical studies on the prevention of medication errors in pediatric care. A further search, using each of the studied interventions as keywords, allowed us to add a further 10 pediatric articles. The scientific quality of all 32 original articles retrieved in this way was assessed (Table 2). To date no meta-analyses on which treatment recommendations or guidelines might be based are available, and none can be produced from the currently available data. This is because there are many factors involved, because individual approaches cannot be compared with each other, and also simply because the definitions used are heterogeneous (6). This article aims to analyze the prescribing process and its sources of errors and so to indicate approaches that might contribute to a reduction in errors.

Measures to improve the quality of drug prescriptions for children and evidence of their effects
Measures to improve the quality of drug prescriptions for children and evidence of their effects
Table 2
Measures to improve the quality of drug prescriptions for children and evidence of their effects

Analysis of the drug prescribing process and sources of error

Determining the indication

Prescription always begins with examination of the indication and consideration of any promising alternatives to drug therapy. In some situations, a child’s proximity to his/her mother may make pharmacological sedation unnecessary. Age group–specific contraindications must also be observed in pediatric care (Table 3).

Examples of age group–specific contraindications for drugs that are unproblematic in adults
Examples of age group–specific contraindications for drugs that are unproblematic in adults
Table 3
Examples of age group–specific contraindications for drugs that are unproblematic in adults

Determining recommended dose

Weight-based recommended doses form the basis of prescription. These can vary significantly according to age group. For example, substantial circulatory depression was observed when 1 mg/kg propofol was administered to preterm infants to induce narcosis (e14). However, no hypotension was described following administration of 3 mg/kg propofol and 2 or 3 µg/kg remifentanil in children between 5 and 10 years of age (e15).

Determining weight

Often, little importance is attached to a child’s actual weight in medical care. In one pediatric emergency department, for instance, only 2% of children were weighed and the weight of all other children was estimated in various ways (e16). Age-related formulae were the most common method used; these are known to be of poor quality (9). For example, the weights of the six-year-old children in the study mentioned above ranged from 19 to 30 kg (e16). In prehospital emergency care too, sufficient importance is not always attached to children’s weight. This is also evident from the fact that the standardized emergency care protocol based on the recommendations of the German Interdisciplinary Association for Intensive and Emergency Care (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin, DIVI), which contains 203 parameters, has no field to indicate weight (e17, e18). In everyday clinical practice, it can also be observed that in individual cases drug doses are even established in the form of a proportion of an adult dose, with no specific estimate of weight.

Dose calculation, preparation

The very need for individual calculation of the required dose entails the possibility of calculation errors (e2). For example, infants’ body weight generally doubles between birth and the age of six months. This means that familiarity with the usual dose cannot be assumed, and even tenfold dosing errors do not seem suspect and occur regularly (2). Determining the correct dose seems to be the most significant step, as this is where the highest error rate is observed (38, e19, e20). A further source of errors is the choice of preparation. As a result of the considerable variation in doses, many drugs are available in various package sizes and concentrations, and diluted forms are produced so that usable volumes can be administered.

Compiling and issuing prescriptions

Communication problems are also responsible for many medication errors (e21). A complete prescription contains both a dosing formula (e.g. in mg/kg) and the absolute dose according to the patient’s body weight (e.g. in mg). It must also state the concentration used (e.g. in mg/mL) and the resulting absolute quantity of the solution to be administered (e.g. in mL). Care must also be taken with similar-sounding names (e.g. esmeron and esmolol) (e22). If a diluted form is to be used, its exact name and preferably also instructions for producing it must be given. In simulated resuscitation events in a pediatric hospital’s emergency department, 17% of prescriptions were incomplete according to this definition (3).

Preparing and administering prescribed drugs

In most clinical situations preparing a drug solution of the required concentration and administering the necessary dose in the form of the indicated quantity is the task of a emergency medical technician. In the prospective observational study mentioned above involving simulated resuscitation events in a pediatric emergency department, the prepared syringes were collected. A concentration that deviated from the stated concentration by more than 50% was found in 7% of the syringes (3).

The effect of care context on error rate

All the sources of error described above become even more significant when urgency is greater and the number of prescriptions is higher. This has been demonstrated in intensive care units for adults (e23) and neonates (e5), for example. In a retrospective cohort study in a pediatric emergency department, 10% of prescriptions were rated as erroneous (38). In prehospital emergency care, even higher rates of dosing errors are to be expected. In addition to the emotional pressure experienced by many emergency physicians (e24), prehospital care structures have neither specialized pediatric staff nor treatment procedures optimized for pediatric patients. In hospitals, control mechanisms involving several persons with comparable skills provide a significant gain in safety; these are also absent in prehospital care. These problems were clearly shown in a prospective study in which correct doses were used in only 34% of prehospital administrations of epinephrine for resuscitation (34). It has also been shown that excessive fatigue among prescribing staff and nighttime hours contribute to higher error rates (38, e25e26).

Interventions for improving drug prescriptions

Below is an outline of strategies to prevent such errors, and where possible an evaluation of their effectiveness on the basis of a comparison of the literature.

Determining indication and dosing recommendations

All staff should have a basic knowledge of age group–specific properties of emergency drugs. Several summaries of pediatric drug therapy are available, and it seems useful to be able to refer to one of these during prehospital care (Table 4). Access to pediatric pharmacological information has been shown to increase the rate of correct dosing (7), even if the information in question is merely a summary table (8). In specific situations it may also be useful to consult the nearest pediatric intensive care unit by telephone.

Examples of short summaries on pediatric drug therapy (in German)
Examples of short summaries on pediatric drug therapy (in German)
Table 4
Examples of short summaries on pediatric drug therapy (in German)

Determining weight

Various authors insist that a child must be weighed before a drug is prescribed (39), but this is often impossible in emergency care. It would be a useful initial step simply to attach sufficient importance to weight. In many cases, a child’s parents are available and can be asked the child’s weight, and this should be done. In a comparison of weight estimates for 410 children, parents were able to estimate weight correctly to within 10% accuracy in 78% of cases (9), and this was far superior to age-related formulae. The next best method is length-related estimating, which determines an average weight (i.e. ideal weight) on the basis of percentiles. This is therefore the method that should be used if it is impossible to weigh a child (percentile curves or pediatric emergency ruler). Dosing according to ideal weight is beneficial even for obese children, as they have a lower proportional extracellular volume by weight, and this is the decisive distribution volume for the dosing of emergency drugs, analgesics, and sedatives (e27).

Dose calculation, preparation

Once dosing recommendations and weight have been determined, the required dose can be calculated. Electronic aids (e.g. a pocket calculator) are useful for this, because they have been shown to minimize calculation errors (11). For example, in one pediatric hospital the use of a computer program to calculate doses halved dosing errors in prescriptions (12). However, any other measure that can reduce the number of steps required in calculation can also reduce the error rate (e28). For example, in a prospective study in the USA 500 prehospital emergency physicians were asked to calculate pediatric prescriptions in a questionnaire, in a quiet, stress-free situation. All the necessary information was always given, and only whole numbers were used. Following randomization, approximately half of the participants were allowed to consult a table for reference (Table 5). Of those without the table, only 65% of the emergency physicians completed the whole questionnaire with no errors, compared to 94% with the table (13).

Reference adaptation of Bernius emergency dosing card (13)
Reference adaptation of Bernius emergency dosing card (13)
Table 5
Reference adaptation of Bernius emergency dosing card (13)

Issuing prescriptions

It is preferable to issue prescriptions in writing whenever possible. This can hardly be guaranteed in acute emergencies. However, at least orally, detailed and comprehensive information as well as all steps of calculation must be communicated. The recipient of the prescription should repeat these in full, as confirmation. It is expected that establishing this type of communication structure will reduce the rate of drug errors (e11, e12), although this has not yet been researched for oral instructions. However, a lower error rate has been recorded following introduction of a written prescription form (Table 6) (1517).

Presciption form after Kozer (15)
Presciption form after Kozer (15)
Table 6
Presciption form after Kozer (15)

Preparing and administering prescribed drugs

Wherever possible, the number of concentrations used should be kept to the minimum required. If drug administration is followed by flushing, in many cases the undiluted drug solution can be used, with small syringes (1 mL syringes calibrated in 0.01 mL increments). Syringes containing various concentrations of the same active substance should be avoided. The necessary solution concentrations must be observed precisely. Commercially preprepared, labeled syringes achieve higher levels of safety, as quality control is incorporated into the manufacturing process (39). A disadvantage of these preprepared syringes is their limited shelf life and high cost. Every preprepared syringe should be labeled clearly; this is an effective check in itself (e29). The use of color-coded stickers, as established in international standard ISO 26825, seems to be beneficial (e30). It has been shown that this type of labeling system can reduce at least mix-ups between drug groups (39). In addition, syringe barcodes that can be read by smart syringe pumps seem to be particularly advisable (18). However, it seems that this measure cannot yet be implemented in prehospital care.

Additional interventions for improving drug prescriptions

Below is a description of possible ways to achieve improvements in drug prescription. These could either not be assigned to any of the points outlined above or represent groups of several subpoints.

Staff training, observation and reporting systems

It is certainly impossible to guarantee comprehensive prehospital emergency care provided by pediatricians and pediatric nursing staff. However, it has been shown more than once that experience and training can reduce error rates. For example, training in both knowledge of pediatric drug therapy and the causes of drug errors and how to resolve them can reduce the rate of prescribing errors (4, 19, 20, 24, 32). Error reporting systems (critical incident reporting system, CIRS) increase the number of errors that are reported and are the subject of constructive discussion in hospitals (e20), and although as yet there is no evidence, this can be expected to reduce errors. However, the introduction of inspections by hospital pharmacists has been shown in itself to reduce the error rate in a neonatal intensive care unit (29). This step was announced to staff and has clearly led to an increase in their levels of vigilance.

Electronic prescription systems

When computer-based prescription systems are used, required doses, routes of administration, and frequencies are entered into a program, and the computer performs the calculation. A system of this kind has been shown to reduce the rate of incomplete prescriptions (21), although in isolation it cannot reduce the rate of dangerous dosing errors (23, e31). The incorporation of a database on pediatric drug therapy that includes information on dosing recommendations and a control mechanism has successfully reduced the number of dangerous dosing errors significantly (23, 25, 26).

The pediatric emergency ruler

The German pediatric emergency ruler (PädNFL, Pädiatrisches Notfalllineal) provides support at all the stages of drug prescription outlined above. In prehospital care in particular, in which some of the measures indicated above to increase prescription safety cannot be implemented due to structural factors, the pediatric emergency ruler may be useful. It makes it possible to estimate patients’ weight accurately, avoiding excessively high dosing as a result of obesity, and provides age group–specific dosing recommendations. Based on standardized drug preparation, the volumes to be administered according to the concentrations used are directly indicated on the pediatric emergency ruler. A majority of the cognitive effort involved in drug prescription is therefore covered by the pediatric emergency ruler, so it is not surprising that the use of a similar tool (the Broselow tape) has already repeatedly been shown to be beneficial in simulated resuscitation events (10). In prehospital pediatric emergency care too, the rate of correct epinephrine doses increased almost twofold when this aid was introduced in a prospective cohort study (34). In addition, length-related tracheal tube selection is superior to age-related selection methods (40). Physiological normal values can also be consulted at a glance, and compliance with these values is essential to an optimum neurological outcome (e32). The demonstrated benefit of this length-based calculation method has led to its use being recommended in the American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care (e33) (Figure 1).

Conclusion

Medication errors pose a substantial danger to all patients, and children in emergencies are exposed to a particularly high risk. It would be desirable and probably also beneficial for there to be intensive, coordinated research on this subject. In general, raising staff’s awareness of this issue and relevant continuing education alone result in lower numbers of dosing errors. The same is true of all measures that lead to a reduction in the cognitive effort required for drug prescription.

Measures to improve the quality of drug prescriptions for children and evidence of their effects
Measures to improve the quality of drug prescriptions for children and evidence of their effects
eTable
Measures to improve the quality of drug prescriptions for children and evidence of their effects

Conflict of interest statement

Dr. Kaufmann possesses a utility patent and receives royalties for the German pediatric emergency ruler (PädNFL).
The other authors declare that no conflict of interest exists.

Manuscript received on 27 February 2012, revised version accepted on 5 June 2012.

Translated from the original German by Caroline Devitt, MA.

Corresponding author:
Dr. med. Jost Kaufmann

Chair of Anesthesiology II

Department of Pediatric Anesthesiology, Witten/Herdecke University

Kinderkrankenhaus Kliniken der Stadt Köln gGmbH

Department for Pediatric Anesthesiology

Amsterdamerstr. 59
50735 Köln, Germany

kaufmannj@kliniken-koeln.de

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eTable:
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Valentin A, Capuzzo M, Guidet B, et al.: Errors in administration of parenteral drugs in intensive care units: multinational prospective study. Bmj 2009; 338: b814. MEDLINE
e24.
Zink W, Bernhard M, Keul W, Martin E, Volkl A, Gries A: [Invasive techniques in emergency medicine. I. Practice-oriented training concept to ensure adequately qualified emergency physicians]. Anaesthesist 2004; 53: 1086–92. MEDLINE
e25.
Hendey GW, Barth BE, Soliz T: Overnight and postcall errors in medication orders. Acad Emerg Med 2005; 12: 629–34. MEDLINE
e26.
Vila-de-Muga M, Colom-Ferrer L, Gonzalez-Herrero M, Luaces-Cubells C: Factors associated with medication errors in the pediatric emergency department. Pediatr Emerg Care 2011; 27: 290–4. MEDLINE
e27.
Luten RC, Zaritsky A, Wears R, Broselow J: The use of the Broselow tape in pediatric resuscitation. Acad Emerg Med 2007; 14: 500–1; author reply 1–2. MEDLINE
e28.
Luten R, Wears RL, Broselow J, Croskerry P, Joseph MM, Frush K: Managing the unique size-related issues of pediatric resuscitation: reducing cognitive load with resuscitation aids. Acad Emerg Med 2002; 9: 840–7. MEDLINE
e29.
Merry AF, Shipp DH, Lowinger JS: The contribution of labelling to safe medication administration in anaesthetic practice. Best Pract Res Clin Anaesthesiol 2011; 25: 145–59. CrossRef MEDLINE
e30.
Sybrecht GW, Prien T: Arzneimittelsicherheit: Standard-Spritzenaufkleber in der Akutmedizin. Dtsch Arztebl 2010; 107: A1031–2. VOLLTEXT
e31.
Walsh KE, Gurwitz JH: Medical abbreviations: writing little and communicating less. Arch Dis Child 2008; 93: 816–7. MEDLINE
e32.
Chambers IR, Jones PA, Lo TY, et al.: Critical thresholds of intracranial pressure and cerebral perfusion pressure related to age in paediatric head injury. J Neurol Neurosurg Psychiatry 2006; 77: 234–40. MEDLINE
e33.
Kleinman ME, Chameides L, Schexnayder SM, et al.: Special Report-Pediatric Advanced Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Pediatrics 2010; 126: e1361–99. MEDLINE
e34.
Macdonald S: Aspirin use to be banned in under 16 year olds. Bmj 2002; 325: 988. CrossRef MEDLINE
e35.
Yis U, Ozdemir D, Duman M, Unal N: Metoclopramide induced dystonia in children: two case reports. Eur J Emerg Med 2005; 12: 117–9. CrossRef MEDLINE
e36.
Promethazine and sudden infant death. Prescrire Int 2006; 15: 226. MEDLINE
e37.
OCEBM Levels of Evidence Working Group. „The Oxford 2011 Levels of Evidence“. Oxford Centre for Evidence-Based Medicine. http://www.cebm.net/index.aspx?o=5653
Institute of Anesthesiology at Witten/Herdecke University, Department of Paediatric Anesthesia, Cologne Children's Hospital: Dr. med. Kaufmann, Dr. med. Laschat, Prof. Dr. med. Wappler
The German pediatric emergency ruler (PädNFL), placed with one end by the heels of a child lying with legs outstretched. Weight, age-appropriate normal values, sizes of equipment, and weight-related doses of emergency drugs can be read off the section that lies by the child’s head
The German pediatric emergency ruler (PädNFL), placed with one end by the heels of a child lying with legs outstretched. Weight, age-appropriate normal values, sizes of equipment, and weight-related doses of emergency drugs can be read off the section that lies by the child’s head
Figure 1
The German pediatric emergency ruler (PädNFL), placed with one end by the heels of a child lying with legs outstretched. Weight, age-appropriate normal values, sizes of equipment, and weight-related doses of emergency drugs can be read off the section that lies by the child’s head
Key messages
PubMed research (database existing since 1963, last accessed in May 2012)
PubMed research (database existing since 1963, last accessed in May 2012)
Table 1
PubMed research (database existing since 1963, last accessed in May 2012)
Measures to improve the quality of drug prescriptions for children and evidence of their effects
Measures to improve the quality of drug prescriptions for children and evidence of their effects
Table 2
Measures to improve the quality of drug prescriptions for children and evidence of their effects
Examples of age group–specific contraindications for drugs that are unproblematic in adults
Examples of age group–specific contraindications for drugs that are unproblematic in adults
Table 3
Examples of age group–specific contraindications for drugs that are unproblematic in adults
Examples of short summaries on pediatric drug therapy (in German)
Examples of short summaries on pediatric drug therapy (in German)
Table 4
Examples of short summaries on pediatric drug therapy (in German)
Reference adaptation of Bernius emergency dosing card (13)
Reference adaptation of Bernius emergency dosing card (13)
Table 5
Reference adaptation of Bernius emergency dosing card (13)
Presciption form after Kozer (15)
Presciption form after Kozer (15)
Table 6
Presciption form after Kozer (15)
Measures to improve the quality of drug prescriptions for children and evidence of their effects
Measures to improve the quality of drug prescriptions for children and evidence of their effects
eTable
Measures to improve the quality of drug prescriptions for children and evidence of their effects
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e23.Valentin A, Capuzzo M, Guidet B, et al.: Errors in administration of parenteral drugs in intensive care units: multinational prospective study. Bmj 2009; 338: b814. MEDLINE
e24.Zink W, Bernhard M, Keul W, Martin E, Volkl A, Gries A: [Invasive techniques in emergency medicine. I. Practice-oriented training concept to ensure adequately qualified emergency physicians]. Anaesthesist 2004; 53: 1086–92. MEDLINE
e25.Hendey GW, Barth BE, Soliz T: Overnight and postcall errors in medication orders. Acad Emerg Med 2005; 12: 629–34. MEDLINE
e26.Vila-de-Muga M, Colom-Ferrer L, Gonzalez-Herrero M, Luaces-Cubells C: Factors associated with medication errors in the pediatric emergency department. Pediatr Emerg Care 2011; 27: 290–4. MEDLINE
e27.Luten RC, Zaritsky A, Wears R, Broselow J: The use of the Broselow tape in pediatric resuscitation. Acad Emerg Med 2007; 14: 500–1; author reply 1–2. MEDLINE
e28.Luten R, Wears RL, Broselow J, Croskerry P, Joseph MM, Frush K: Managing the unique size-related issues of pediatric resuscitation: reducing cognitive load with resuscitation aids. Acad Emerg Med 2002; 9: 840–7. MEDLINE
e29.Merry AF, Shipp DH, Lowinger JS: The contribution of labelling to safe medication administration in anaesthetic practice. Best Pract Res Clin Anaesthesiol 2011; 25: 145–59. CrossRef MEDLINE
e30.Sybrecht GW, Prien T: Arzneimittelsicherheit: Standard-Spritzenaufkleber in der Akutmedizin. Dtsch Arztebl 2010; 107: A1031–2. VOLLTEXT
e31.Walsh KE, Gurwitz JH: Medical abbreviations: writing little and communicating less. Arch Dis Child 2008; 93: 816–7. MEDLINE
e32.Chambers IR, Jones PA, Lo TY, et al.: Critical thresholds of intracranial pressure and cerebral perfusion pressure related to age in paediatric head injury. J Neurol Neurosurg Psychiatry 2006; 77: 234–40. MEDLINE
e33.Kleinman ME, Chameides L, Schexnayder SM, et al.: Special Report-Pediatric Advanced Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Pediatrics 2010; 126: e1361–99. MEDLINE
e34.Macdonald S: Aspirin use to be banned in under 16 year olds. Bmj 2002; 325: 988. CrossRef MEDLINE
e35.Yis U, Ozdemir D, Duman M, Unal N: Metoclopramide induced dystonia in children: two case reports. Eur J Emerg Med 2005; 12: 117–9. CrossRef MEDLINE
e36. Promethazine and sudden infant death. Prescrire Int 2006; 15: 226. MEDLINE
e37.OCEBM Levels of Evidence Working Group. „The Oxford 2011 Levels of Evidence“. Oxford Centre for Evidence-Based Medicine. http://www.cebm.net/index.aspx?o=5653