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Newborns should be receiving premedication before elective intubation.

Endotracheal intubation is a common neonatal procedure and essential for the provision of neonatal intensive care. The procedure induces noxious stimuli often associated with adverse physiological events such as raised intracranial pressure, [1] hypoxaemia and cardiovascular instability. [2] Premedication regimens may include a vagolytic to reduce vagal-induced bradycardia, a narcotic/sedative agent that attenuates increases in systemic blood pressure, and a muscle relaxant that attenuates increases in intracranial pressure. [3]

Recent studies have shown that premedication for elective and semi-urgent intubation of infants significantly improves intubation conditions, decreases the time and number of attempts needed to complete the intubation procedure, and minimises the potential for intubation-related airway trauma.'4-61 However, despite the growing body of evidence and acceptance of premedication as a standard of care, its use is still not universal, and wide variations occur in practice. [7,8]

Premedication practices have been surveyed in Europe, [7,9,10] North America [8,11] and Australia. [12] The European surveys had a profound effect on current practice. Whyte et al. [7] demonstrated in a study conducted in 1998 that 63% of UK neonatal units did not use premedication prior to intubation, their study prompting much discussion. A decade later, when the survey was repeated, [greater than or equal to] 90% of neonatal units had adopted premedication as standard of care. [9,10]

Because current neonatal premedication practices have not previously been surveyed in South Africa (SA), we designed a survey with the objective of determining the current practice and standard of care. This survey may provide data that could inform the design of collaborative trials and/or stimulate debate that ultimately leads to change and standardisation of practice.


The study was designed as a cross-sectional survey of clinicians working in SA state and private neonatal intensive care units. This research was approved by the Human Research Ethics Committee, Faculty of Health Sciences, University of Cape Town.

Potential participants were identified from an online listing of 147 neonatal intensive care units in hospitals across SA on the Medpages directory website. [13] The names and contact details of the clinicians working in those units were obtained by searching the websites of the respective hospitals. Additional names and contact details of clinicians involved in neonatal care were obtained from a local departmental database. Clinicians who did not treat neonates in their practice were excluded. Clinicians did not receive incentives to participate in the survey.

The survey questionnaire was created and hosted using Survey Monkey, an online survey website. The questionnaire enabled compilation of data regarding use of premedication and whether a written policy existed for sedating preterm infants before elective or semi-elective intubation. The questionnaire was designed to determine which agent/s were most used for premedication, as well as the doses used. The questionnaire was brief, taking no more than 3 minutes to complete. Each question addressed a single point and in most cases required a 'yes' or 'no' response. An e-mail containing an individualised link to the survey was sent to 481 clinicians on 1 October 2013. The Survey Monkey collector tool collected all responses anonymously and automatically sent reminder e-mails to those who had not responded. Survey collection closed on 14 November 2013.

Data analysis

Responses were exported to a Microsoft Excel file. Data were analysed with Stata version 12 (Stata Corporation, USA). Chi-square and Fisher's exact tests were used for comparison of categorical variables. Descriptive results were expressed as numbers and proportions (%). A p-value of <0.05 was considered significant. Results

We received responses to 136 of the 481 emails sent (28.3%). The characteristics of the respondents surveyed are shown in Table 1. Sixty-six responses (54.1%) were from clinicians in the private sector and 56 (45.9%) from those in the state sector. The majority of respondents were paediatricians or neonatologists. The majority of paediatricians (76.0%) worked in the private sector, whereas 78.6% of neonatologists worked in the state sector, typically in medium-sized neonatal units with six to ten beds.

A subgroup analysis comparing premedication practices between the public and private sectors is reported in Table 2. A written policy was used by a minority of clinicians, more often in the public sector (p < 0.0001).

Premedication prior to intubation was practised by 71.9% of respondents; however, only 38.5% of neonatal units had a written policy. The respondents routinely used sedatives for premedication, but not muscle relaxants or atropine. These data are reported in Table 3 and Fig. 1. Midazolam, morphine and ketamine were the most commonly used sedative agents (Fig. 2). When muscle relaxants were administered, suxamethonium (95.2%) was the muscle relaxant of choice.

Table 4 illustrates varied combinations of agents or single agents used for premedication. Seven premedication drugs were used in 16 different combinations/ regimens, utilising one to three drugs. Midazolam was the drug most commonly used as a single agent.

Table 5 illustrates the drug dose ranges. Most respondents stated specific doses for the choice of drug used: 33.3% specified a morphine dose of 0.1 mg/ kg, whereas 39.0% said that they would administer a dose of 0.2 mg/kg. Midazolam dosing varied, respondents using doses of 0.1 mg/kg (36.4%), 0.15 mg/kg (13.6%), 0.2 mg/kg (22.7%) and 0.4 mg/kg (4.5%). For suxamethonium, 55.0% of respondents used a dose of 2 mg/kg.


A greater understanding of neonatal pain and the knowledge that noxious stimuli such as intubation may have long-term deleterious effects [13] have prompted consensus statements [14-16] advocating the use of premedication as standard of care.

This study illustrates that almost 30% of the SA clinicians surveyed were not administering premedication to infants before elective or semi-elective intubation, in stark contrast to practice in the UK or Australasia, where recent surveys [9,10,12] indicate that >90% of units are providing premedication. No consensus exists regarding the choice of agent/s, their dose/s or the ideal route of administration, [6] mirroring the findings of the present study and other surveys. [7-12]

Suxamethonium, as in other national surveys, [7-12] was the most commonly used muscle relaxant and is currently considered to be the best choice [17] because of its rapid onset, short duration of action and good side-effect profile.

In contrast to findings in the other national surveys, [7-12] midazolam was the preferred sedative in this SA study. Many participants used midazolam as the only premedication drug. Midazolam, a short-acting benzodiazepine with sedative properties, is inappropriate [17] because it has no analgesic properties. There are additional pitfalls to the use of midazolam as a single agent for intubation: Harte et al., [18] examining the haemodynamic effect and pharmokinetic properties of midazolam, demonstrated no mitigation of the physiological changes attributed to intubation and found that the drug was associated with serious adverse effects during intubation. The use of midazolam has also been associated with hypotension and adverse neurological outcomes. [19,20] A Cochrane review found no evidence to support the use of midazolam as a sedative for infants, particularly preterm ones. [21] Infants receiving midazolam had longer hospital stays, and there were more adverse effects in the midazolam group when compared with placebo. [21]

A survey of premedication practices in the UK by Singh et al. [22] found the combination of fentanyl, atropine and suxamethonium to be the most common, followed by morphine, atropine and suxamethonium. A recent randomised controlled trial (RCT) in which either morphine alone or placebo was given 5 minutes before intubation demonstrated inability of morphine to reduce either the adverse physiological changes attributed to intubation or the time required to complete the intubation process. [23] Moreover, safety concerns regarding the use of morphine for premedication in preterm infants have been raised, as it has been associated with prolonged amplified electroencephalography (aEEG) depression, independent of blood pressure changes. [24] Fentanyl is preferred to morphine, as its more rapid onset of action may improve pain control during intubation. [25] Hamon et al. [26] have shown that short-term fentanyl infusion in preterm infants is not associated with changes in systemic and cerebral perfusion pressures.

Propofol was listed by one respondent as their premedication drug of choice. Propofol is a hypnotic agent without anaesthetic properties. Spontaneous breathing effort is maintained during the intubation process. Ghanta et al. [5] compared propofol with a combination of morphine, atropine and suxamethonium, which took 5 times longer to prepare. They reported faster intubation times, better oxygen saturation maintenance and shorter recovery times in the propofol group, and there was no difference in bradycardia or hypotension between the two groups. [5] A paucity of data remains regarding the use of propofol in infants; the Cochrane review by Shah et al. [27] only included the 63 infants in Ghanta et al.'s RCT. There are also significant concerns regarding the safety of propofol, Welzing et al. [28] demonstrating a significant drop in arterial blood pressure when propofol was injected as a fast push. Current pharmacokinetic studies on the use of propofol in infants indicate marked inter-individual variability and reduced clearance of propofol.'291 The Exploratory Propofol Dose Finding Study in Neonates (NEOPROP) is currently under way and aims to evaluate pharmacokinetics and pharmacodynamics of propofol and to determine the optimal dose in infants.'301 Following identification of a safe dose, RCTs are needed to assess safety and efficacy of propofol, both as a single agent and in combination with an analgesic agent.

The UK and Australasian surveys enjoyed high response rates from clinicians surveyed. The low rate of response to the current survey may not reflect true premedication practices, as SA doctors respond poorly to mail surveys despite high internet penetration, which influenced our decision to conduct a web-based survey. [31]

This is the first study to survey premedication practice prior to elective neonatal intubation in SA. The findings highlight a wide variation in practices and the need for written policies, particularly in the private sector. Further research is needed to determine the outcomes associated with premedication, the most appropriate agent/s and their optimal dose/s. A national network of neonatal units needs to be established to ensure representative data collection. The findings of this study could be used to inform local collaborative trials aimed at studying premedication for intubation in the neonatal period. Importantly, this survey may stimulate debate and discussion, culminating in a national premedication practice guideline.

Accepted 14 August 2014.

Acknowledgements. The authors thank all the participants for providing data for this survey.

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[12.] Wheeler B, Broadbent R, Reith D. Premedication for neonatal intubation in Australia and New Zealand: A survey of current practice. J Paediatr Child Health 2012; 48(11):997-1000. [http://]

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M S Raban, Y Joolay, A R Horn, M C Harrison

Dr Shukri Raban completed his neonatal fellowship at Groote Schuur Hospital, Cape Town, South Africa, and qualified as a neonatologist in 2012. His main interest is improving infant nutrition, and he is currently involved in research to improve breastmilk provision in the neonatal unit. Additional interests include clinical governance, infection surveillance and less invasive measures to provide surfactant to infants. Dr Yaseen Joolay is a neonatologist at Groote Schuur Hospital. An avid fan of innovative technologies, his current interests are quality improvement, standardisation of practices and the appropriate application of technologies in neonatal care. Assoc. Prof. Alan Horn is a neonatologist at Groote Schuur Hospital. He was recently awarded a PhD for his research on hypoxic ischaemic encephalopathy - he has a special interest in the use of amplified electroencephalography and therapeutic cooling and has published work in this field. Assoc. Prof. Michael Harrison is a neonatologist and head of the Division of Neonatal Medicine, Groote Schuur Hospital and Department of Paediatrics, Faculty of Health Sciences, University of Cape Town, to which all the authors are affiliated. He completed his paediatric and subspecialty training in the UK. He is an advocate for clinical governance and places strong emphasis on translational research.

Corresponding author: M S Raban (
Table 1. Characteristics of neonatal
units surveyed (N=136)

                          n (%)

Nature of practice
  Private health sector   66 (54.1)
  Public health sector    56 (45.9)
  Medical officer         9 (6.6)
  Registrar               6 (4.4)
  Paediatrician           78 (57.4)
  Neonatologist           28 (20.6)
  Other specialist        5 (3.7)
  Not a medical doctor    10 (7.4)
ICU beds
  0                       3 (2.5)
  1-5                     35 (28.7)
  6-10                    50 (41.0)
  >10                     34 (27.9)

Table 2. Subgroup analysis

Premedication practice    Private sector,   Public sector,   p-value
                          n (%)             n (%)

Written policy present    15 (31.9)         32 (68.0)        <0.0001
Routine use of any        46 (52.9)         41 (47.1)        0.8
premedication agent
Routine use of            25 (45.5)         30 (54.6)        0.13
Routine use of            10 (47.6)         11 (52.4)        0.62
  muscle relaxants
Routine use of atropine   15 (45.5)         18 (54.6)        0.315

Table 3. Premedication practices

Premedication practice            Yes, n (%)   No, n (%)

Written policy                    47 (38.5)    75 (61.5)
Use of premedication              87 (71.9)    34 (28.1)
Routine use of sedatives          55 (63.2)    32 (36.8)
Routine use of muscle relaxants   21 (24.4)    65 (75.6)

Table 4. Combinations of premedication used

Agents                                        Respondents (N=87)
                                              n (%)

Midazolam + suxamethonium + atropine          1 (1.15)
Midazolam + atropine (when bradycardic)       5 (5.7)
Midazolam alone                               16 (18.4)
Morphine + suxamethonium + atropine           7 (8.0)
Morphine + atropine                           2 (2.3)
Morphine alone                                7 (8.0)
Morphine + atropine (when bradycardic)        2 (2.3)
Ketamine + suxamethonium + atropine           6 (6.9)
Ketamine + cisatricurium + atropine           1 (1.15)
Ketamine + atropine                           4 (4.6)
Fentanyl + suxamethonium + atropine           1 (1.15)
Propofol alone                                1 (1.15)
Suxamethonium alone                           1 (1.15)
Suxamethonium + atropine                      4 (4.6)
Atropine alone                                7 (8.0)
Atropine when bradycardic                     3 (3.4)
Answered 'yes' for premed, no agents ticked   19 (21.8)

Table 5. Doses for premedication drugs

Drug            Dose

Fentanyl        10 [micro]g/kg
Ketamine        1-2 mg/kg
Midazolam       0.05-0.4 mg/kg
Morphine        0.05-0.2 mg/kg
Propofol        1-2 mg/kg
Suxamethonium   1-2 mg/kg

Fig. 1. Atropine use for premedication.

Only when bradycardic   11.8%
Never                   49.4%
Routine                 38.8%


Note: Table made from bar graph.

Fig. 2. Sedative agents used.

Propofol    1.9%
Ketamine    20.8%
Midazolam   41.5%
Fentanyl    1.9%
Morphine    34%


Note: Table made from bar graph.
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Author:Raban, M.S.; Joolay, Y.; Horn, A.R.; Harrison, M.C.
Publication:South African Medical Journal
Article Type:Report
Geographic Code:6SOUT
Date:Dec 1, 2014
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