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\begin{document}

\title{Off-label use of dexmedetomidine in paediatric anaesthesiology: an
international survey of 791 (paediatric) anaesthesiologists}



\author[1]{Camille van Hoorn}%
\author[2]{Robert Flint}%
\author[3]{Justin Skowno}%
\author[4]{Paul Davies}%
\author[5]{Thomas Engelhardt}%
\author[6]{Kirk Lalwani}%
\author[7]{Olutoyin Olutoye}%
\author[1]{Erwin Ista}%
\author[1]{Jurgen de Graaff}%
\affil[1]{Erasmus MC Sophia Children Hospital}%
\affil[2]{Erasmus MC}%
\affil[3]{Children's Hospital at Westmead}%
\affil[4]{The Royal Children's Hospital Melbourne}%
\affil[5]{Royal Aberdeen Children's Hospital}%
\affil[6]{Oregon Health \& Science University University Hospital}%
\affil[7]{Texas Children's Hospital}%


\vspace{-1em}



  
  \date{May 07, 2024}


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\selectlanguage{english}
\begin{abstract}
The aim of this international study is to gain information on
dexmedetomidine prescription by paediatric anaesthesiologists. We
composed an online survey containing questions about the prescription
rate of dexmedetomidine, administration route and dosage, adverse drug
reactions, education on the drug and overall experience. Members of
specialist paediatric anaesthesia societies of Europe (ESPA,n=849), New
Zealand and Australia (SPANZA,n=320), Great Britain and Ireland
(APAGBI,n=872) and the United States (SPA,n=3130) were e-mailed a link
to this survey; responses were collected July and August 2019. Eight
hundred and fifty-one invitees (851/5171,17\%) responded, of whom 60 did
not report their countries and were therefore excluded from the
analyses. The ESPA members' response rate was 25\%, SPANZA35\%,
APAGBI15\% and SPA10\%. Dexmedetomidine is prescribed by 70\% of all
respondents (ESPA 121/229,53\%;SPANZA 77/111,69\%;APAGBI 44/129,34\% and
SPA 310/322,96\%) of whom 73\% has access to mostly local protocols.
Differences in the use were mainly found in the age of the patients
receiving dexmedetomidine (SPA primarily \textless{}1 year, others
primarily \textgreater{}1 year). Members of SPANZA, APAGBI and SPA had
not noted adverse drug reactions, although 61\% of ESPA members had
noted bradycardia. The majority of SPA respondents were not aware of any
contraindications, whereas members from all other societies were aware
of these. Although an on-label paediatric indication and clinical
evidence have yet been lacking, many anaesthesiologists use
dexmedetomidine in paediatrics for premedication, procedural sedation,
ICU sedation and anaesthesia. The large intercontinental differences in
dexmedetomidine prescription call for consensus and worldwide education
on the optimal use of dexmedetomidine in paediatric practice.%
\end{abstract}%



\sloppy


\textbf{Off-label use of dexmedetomidine in paediatric anaesthesiology:
an international survey of 791 (paediatric) anaesthesiologists}

Camille E van Hoorn\textsuperscript{1,2}

Robert B Flint\textsuperscript{3,4}

Justin Skowno\textsuperscript{5}

Paul Davies\textsuperscript{6}

Thomas Engelhardt\textsuperscript{7,8}

Kirk Lalwani\textsuperscript{9}

Olutoyin Olutoye\textsuperscript{10}

Erwin WG Ista\textsuperscript{11,12}

Jurgen C de Graaff\textsuperscript{1}

\begin{enumerate}
\tightlist
\item
  Department of Anaesthesiology, Erasmus MC-Sophia Children's Hospital,
  Rotterdam, The Netherlands
\item
  Department of Paediatric Surgery, Erasmus MC-Sophia Children's
  Hospital, Rotterdam, The Netherlands
\item
  Department of Paediatrics, Division of Neonatology, Erasmus MC, Sophia
  Children's Hospital, Rotterdam, The Netherlands.
\item
  Department of Pharmacy, Erasmus MC, University Medical Centre
  Rotterdam, The Netherlands.
\item
  Department of Anaesthesiology, Children's Hospital at Westmead,
  University of Sydney, Sydney, Australia
\item
  Department of Anaesthesia and Pain management, The Royal Children's
  Hospital, Melbourne, Australia
\item
  Department of Anaesthesia, Royal Children's Hospital Aberdeen and
  School of Medicine, University of Aberdeen, Aberdeen, UK
\item
  Department of Anaesthesia, McGill University Health Center, Montreal
  Children's Hospital, Montreal, QC, CA.
\item
  Department of Anaesthesiology and Paediatrics, Oregon Health and
  Science University, Portland, USA
\item
  Department of Anaesthesiology, Peri-operative and Pain Medicine, Texas
  Children's Hospital, USA
\item
  Department of Internal Medicine - Nursing Science, Erasmus MC,
  University Medical Centre Rotterdam, the Netherlands
\item
  Department of Paediatric Surgery, Paediatric Intensive Care, Erasmus
  MC-Sophia Children's Hospital, Rotterdam, The Netherlands
\end{enumerate}

Corresponding author: Camille E van Hoorn ErasmusMC-Sophia Children's
Hospital Department of Anaesthesiology, Department of Paediatric Surgery
PO Box: 2060 3000 CB Rotterdam, The Netherlands Phone: +31 10 703 60 20
E-mail: c.vanhoorn@erasmusmc.nl

Running head: Dexmedetomidine in paediatric anaesthesia

Keywords: anaesthesia, paediatrics, dexmedetomidine, pharmacology, drug
prescriptions, off-label use

What is already known about this subject: - Anaesthesiologists are
searching for new neuroprotective drugs for general anaesthesia, of
which dexmedetomidine might be one. - Due to its haemodynamic stability
and absence of respiratory depressions, dexmedetomidine is increasingly
prescribed off-label in children as premedication, for ICU sedation,
procedural sedation and anaesthesia.

What this study adds: - In spite of its off-label status,
dexmedetomidine is commonly used in paediatric practice all over the
world, mainly for procedural sedation and as premedication for
anaesthesia. - Ages of the patients receiving dexmedetomidine differ
between continents. - Intercontinental sharing of experience is required
to develop dosing recommendations, protocols and teaching opportunities
for (procedural) sedation and anaesthesia with dexmedetomidine.

\section*{Abstract}

{\label{abstract}}

\textbf{Aim}

The aim of this international study is to gain information on
dexmedetomidine prescription by paediatric anaesthesiologists.

\textbf{Methods}

We composed an online survey containing questions about the prescription
rate of dexmedetomidine, administration route and dosage, adverse drug
reactions, education on the drug and overall experience. Members of
specialist paediatric anaesthesia societies of Europe (ESPA,n=849), New
Zealand and Australia (SPANZA,n=320), Great Britain and Ireland
(APAGBI,n=872) and the United States (SPA,n=3130) were e-mailed a link
to this survey; responses were collected July and August 2019.

\textbf{Results}

Eight hundred and fifty-one invitees (851/5171,17\%) responded, of whom
60 did not report their countries and were therefore excluded from the
analyses. The ESPA members' response rate was 25\%, SPANZA35\%,
APAGBI15\% and SPA10\%. Dexmedetomidine is prescribed by 70\% of all
respondents (ESPA 121/229,53\%;SPANZA 77/111,69\%;APAGBI 44/129,34\% and
SPA 310/322,96\%) of whom 73\% has access to mostly local protocols.
Differences in the use were mainly found in the age of the patients
receiving dexmedetomidine (SPA primarily \textless{}1 year, others
primarily \textgreater{}1 year). Members of SPANZA, APAGBI and SPA had
not noted adverse drug reactions, although 61\% of ESPA members had
noted bradycardia. The majority of SPA respondents were not aware of any
contraindications, whereas members from all other societies were aware
of these.

\textbf{Conclusions}

Although an on-label paediatric indication and clinical evidence have
yet been lacking, many anaesthesiologists use dexmedetomidine in
paediatrics for premedication, procedural sedation, ICU sedation and
anaesthesia. The large intercontinental differences in dexmedetomidine
prescription call for consensus and worldwide education on the optimal
use of dexmedetomidine in paediatric practice.

\section*{Introduction}

{\label{introduction}}

Dexmedetomidine is increasingly used in children for premedication,
sedation in the intensive care unit (ICU), procedural sedation, and
anaesthesia, but also to prevent postoperative agitation, nausea and
vomiting.\textsuperscript{1,2} Dexmedetomidine is an alpha-2
adrenoceptor agonist that provides adequate sedation with facilitated
arousal and analgesia without respiratory depression. Dexmedetomidine
offers advantages over traditional anaesthetics for its hemodynamic
stability, sedative properties and multimodal pain
management.\textsuperscript{3,4} Its colourless and odourless properties
make it suitable for paediatric intranasal administration as
premedication. Furthermore, dexmedetomidine ameliorates separation
anxiety in children.\textsuperscript{5,6}

Despite the lack of evidence and off-label use of dexmedetomidine for
anaesthesia in patients younger than 18 years of age, the worldwide use
of dexmedetomidine for paediatric anaesthesia is still
increasing.\textsuperscript{7,8} Experimental research has shown that
dexmedetomidine may have a neuroprotective effect when co-administered
with other anaesthetic medications.\textsuperscript{9,10} However,
evidence is lacking from clinical studies and randomized controlled
trials on the short- and long-term effects of dexmedetomidine use in
children undergoing general anaesthesia or receiving prolonged
dexmedetomidine infusions. Multiple ongoing studies in children
investigate the relationship between dexmedetomidine-based general
anaesthesia and long-term neurodevelopmental
outcomes.\textsuperscript{4,11}

Furthermore, dosing protocols for children have not yet been published,
and an international consensus on the use of dexmedetomidine in
paediatrics is missing.\textsuperscript{12-16} Incorrect application
could lead to yet unknown adverse long-term effects. Therefore,
overexposure to the drug should be avoided.

We postulated that dexmedetomidine is frequently used in paediatric
anaesthesia without a structured implementation procedure including, for
example, education and protocols, which leads to large application
differences. We performed a survey of international paediatric
anaesthesia specialist societies in order to gather information on the
use of dexmedetomidine in children by paediatric anaesthesiologists
worldwide and identify areas of future need for safe and effective use
of dexmedetomidine in children.

\section*{Methods}

{\label{methods}}

We performed an online survey on the use of dexmedetomidine in
paediatric anaesthesiology, starting July 16\textsuperscript{th} 2019
and with closing date August 16\textsuperscript{th}, 2019. The target
response rate was 25\%.

Survey respondents were recruited from the following societies for
paediatric anaesthesiologists: European Society for Paediatric
Anaesthesiology (ESPA), Society for Paediatric Anaesthesia in New
Zealand and Australia (SPANZA), Association of Paediatric Anaesthetists
of Great Britain and Ireland (APAGBI), and Society for Paediatric
Anesthesia (SPA). The boards of these societies were invited to
distribute a survey, described below, amongst their members via an
e-mail with a link to the survey. ESPA, APAGBI and SPA sent an e-mail
with the link to the survey to all members. SPANZA mentioned the survey
and link in a newsletter. ESPA and SPANZA sent a reminder one month
later. APAGBI and SPA have email usage protocols for survey distribution
in place, which do not provide for reminders.

\emph{Survey}

Experts in the field of paediatric anaesthesia developed a 16-question
survey to collect information on the use of dexmedetomidine in
paediatric anaesthesiology care. The items addressed whether the
respondent regularly prescribes dexmedetomidine to children, perceived
barriers for the use of dexmedetomidine in practice, in what setting
dexmedetomidine was used, the availability of a local protocol, how the
respondent had been educated on dexmedetomidine in paediatrics, and
clinical experiences with the drug, such as adverse events (survey in
Supplementary Data).

The survey was designed to be completed anonymously within 10 minutes by
every anonymous participant. It was delivered through Limesurvey
(Limesurvey GmbH, Hamburg, Germany) secure web application for building
and managing online surveys and databases.\textsuperscript{17} The
survey was tested among paediatric anaesthesiologists at the Erasmus
MC-Sophia Children's Hospital Rotterdam. Following this test, some of
the questions were adjusted for improvement.

\emph{Analysis}

The survey data were exported from Limesurvey to Microsoft Excel Version
16.32 (Microsoft Corporation, Redmond, Washington, USA) and SPSS
Statistics Version 24 (IBM Corporation, Armonk, NY, USA) to perform
descriptive statistical analysis. SPSS was used to compare the groups
and summarize the data. Due to the explorative nature of the study, no
comparative statistics were performed.

Incomplete responses with at least 40\% completion were still included
for analysis. The numbers of respondents per question were determined in
order to provide accurate response rates per question.

Responses of respondents who had not stated the country of practice were
excluded from analysis because these responses could not be assigned to
a societal group.

Questions asked regarding experience with adverse drug reactions were
not specified as to whether these reactions were experienced once or
that these were experienced more frequently.

\section*{Results}

{\label{results}}

In total 5171 society members received an invitation (Figure 1). The
number of anaesthesiologists who were members of multiple societies was
unknown. Sixty respondents were excluded because the country of
practice. The overall response was 17\% and varied from 35\% (SPANZA) to
10\% (SPA) among the various societies (Table 1). Seventy-five
incomplete surveys were included for analysis. No incomplete surveys
were excluded due to \textgreater{}40\% completion of the survey.
Respondents who did not answer a specific question were left out of
consideration regarding this question, as reflected in the Tables 1, 3
and 4. Across all societies, most respondents worked in a tertiary
hospital as a full-time paediatric anaesthesiologist (693/791, 88\%).
Respondents had practised as a physician for a median duration of 12
years {[}IQR 6-21{]}.

Almost all (96\%) SPA respondents used dexmedetomidine in paediatric
practice (310/322,), versus 69\% of SPANZA respondents. ESPA respondents
and APAGBI respondents did not use dexmedetomidine as often: 53\% and
34\%, respectively (Table 1).

\textbf{Respondents who use dexmedetomidine}

Overall, seventy percent of the respondents used dexmedetomidine in
paediatric practice. A protocol was not available for members of ESPA
(57/121, 47\%) and SPANZA (33/77, 43\%), whereas nearly all SPA members
(285/310, 92\%) had access to a protocol, as well as the majority of the
APAGBI members (27/44, 61\%). The drug was used for children of all
ages: SPA members used dexmedetomidine mainly in patients younger than 1
year of age, whereas all other respondents used dexmedetomidine mainly
in patients older than 1 year of age. Overall, dexmedetomidine was
mostly used for procedural sedation (375/552, 68\%), as reported by ESPA
respondents (78/121, 65\%) and SPA respondents (253/310, 82\%). The main
indication for members of SPANZA (62/77, 81\%) and members of APAGBI
(30/44, 68\%) was premedication.

Broad ranges of dosages were reported for the use of dexmedetomidine for
different applications (Table 2). For premedication, the most frequently
used dose was 2.0 ug/kg intranasal bolus administration. For procedural
sedation, intensive care sedation, anaesthesia and postoperative
analgesia an intravenous infusion was the most frequently used route of
administration. Dosages for intravenous administration differed widely
(Table 2). Oral and intramuscular administration were reported as well.

The arguments to start using dexmedetomidine in paediatric practice were
fewer cases of emergence delirium compared to traditionally used
anaesthetics (273/552, 50\%), and fewer respiratory complications
(222/552, 40\%). The SPA respondents mainly reported fewer emergence
delirium cases (143/310, 46\%), the ESPA respondents fewer respiratory
complications (79/121, 65\%). The APAGBI respondents (24/44, 55\%) and
SPANZA respondents (49/77, 64\%) mainly reported a good profile for
premedication (Figure 2). Few respondents had started using
dexmedetomidine for its opioid sparing effect. Fifty-six respondents
reported they had received specific training or training though a
protocol. Others had individually consulted relevant literature (n=98);
had discussed the application with colleagues (n=79) or had learned to
use dexmedetomidine via trial and error (n=50).

The most commonly observed adverse drug reactions were bradycardia
(n=129) and nausea (n=99). However, many respondents from all societies
(275/552, 50\%) had not observed adverse drug reactions. Respondents
from the SPA were not familiar with contraindications (286/310, 92\%),
but the majority of respondents from other societies (67\%) were aware
of contra-indications for the use of dexmedetomidine in paediatric care
(Table 3).

\textbf{Respondents who do not use dexmedetomidine}

In total 206 of the 791 respondents (26\%) did not use dexmedetomidine
in paediatric care, mainly members of ESPA (90/229, 39\%) and APAGBI
(80/129, 62\%) (Table 4). Most of them had not been educated in the use
of dexmedetomidine (182/206, 88\%), but were familiar with the drug
(89/229, 49\%). Lack of education was one of the main reasons not to use
dexmedetomidine in paediatric practice (99/206, 48\%). Other perceived
barriers to using dexmedetomidine were the absence of local protocol
(95/206, 46\%), and no consensus among local staff (68/206, 33\%)
(Figure 3). Furthermore, for 46 of these 206 respondents (22\%) the drug
was not available; mainly reported by APAGBI respondents: 34/80, 43\%)
The majority of non-users (174/206, 85\%) were willing to start using
dexmedetomidine for premedication (126/174, 72\%) and procedural
sedation (133/174, 76\%, Table 4). The most important reasons for the
willingness to start using dexmedetomidine were the benefits (82/174,
47\%) and the safer alternative to the currently used drugs (38/174,
22\%). Reasons for not being willing to start using dexmedetomidine
(29/206, 14\%) were the availability of better alternatives (7/29,
24\%), no need (9/27, 31\%), and need for more individual and general
experience with dexmedetomidine (7/29, 24\%).

\section*{Discussion}

{\label{discussion}}

This international survey revealed that despite the off-label use in
children, dexmedetomidine is frequently used in paediatric
anaesthesiology settings, even without the availability of national or
local protocols. The main indications were premedication, procedural
sedation and IC sedation. Most of the anaesthesiologists who used
dexmedetomidine reported absence of adverse drug reactions, as well as
awareness of contraindications for the use in paediatrics.

A prospective pilot study showed that dexmedetomidine-based anaesthesia
creates satisfactory conditions for paediatric
surgery.\textsuperscript{4} Dexmedetomidine proved to be useful for
various types of surgical procedures, such as airway procedures,
neurosurgery, cardiac surgery and ambulatory
procedures.\textsuperscript{18} Dexmedetomidine has not been approved
for use in paediatric care in any country worldwide, which would explain
why structured education of paediatric anaesthesiologists on its use by
manufacturers is lacking. Only 56 respondents (10\%)who use
dexmedetomidine had received such education. Most respondents did not
have access to structured education and taught themselves by reading
scientific papers, discussing with colleagues and/or were self-taught.
Respondents from the SPA primarily used dexmedetomidine in patients
younger than 1 year of age, whereas respondents from other societies
mainly used it in patients older than 1 year of age. This discrepancy
might be related to the interpretation of the 2016 FDA statement
concerning the effects of anaesthesia on the young brain; i.e., children
younger than 3 years of age.\textsuperscript{19} Shortly thereafter, a
consensus statement for European anaesthesiologists concluded that there
was no compelling evidence to change anaesthetic practice, but that
unnecessary procedures should be avoided.\textsuperscript{20} These
conflicting statements may have had effects on the change of current
practice. Since anaesthesiologists in the USA have been warned for the
effects on the young brain, it is likely that they would search for a
less neurotoxic alternative to the traditional anaesthetics --and use
this alternative in the young patients. This may also explain why
respondents who do not use dexmedetomidine are willing to start using it
as an alternative to the currently used anaesthetics, as dexmedetomidine
is thought not to be neurotoxic and provides satisfying sedation. Other
different indications reported by the respondents from the different
societies cannot be explained by the issued warnings. SPANZA and APAGBI
members used dexmedetomidine mainly for premedication, whereas ESPA and
SPA members used it mainly for procedural sedation. In the present
survey study, the opioid-sparing effect was another reason for some
anaesthesiologists to start using dexmedetomidine in paediatric
practice. Administration of dexmedetomidine intraoperatively has been
associated with a lesser need for postoperative analgesia and a lesser
need for fentanyl intraoperatively.\textsuperscript{21-24}

Our survey showed that dosing regimens for paediatric care differ
widely. Studies describing the pharmacokinetics of dexmedetomidine
indicate that children would require a higher dosage per kg bodyweight
compared to adults to achieve comparable exposure, due to a larger
volume of distribution in children.\textsuperscript{25} A previous study
described the off-label use of dexmedetomidine in paediatric care within
the European Union (EU), indicated for ICU sedation, anaesthesia and
procedural sedation.\textsuperscript{7} In the EU, a maximum infusion
rate of 1.4\selectlanguage{greek}μ\selectlanguage{english}g*kg\textsuperscript{--1}*h\textsuperscript{--1} is approved
for adult sedation; however, a recently published study in Europe showed
that infusion rates exceeding
1.4\selectlanguage{greek}μ\selectlanguage{english}g*kg\textsuperscript{--1}*h\textsuperscript{--1} were used in 11\%
of children.\textsuperscript{7} Our study shows a similar practice:
reported infusion rates ranged from 0.1
\selectlanguage{greek}μ\selectlanguage{english}g*kg\textsuperscript{--1}*h\textsuperscript{--1} to 3.0
\selectlanguage{greek}μ\selectlanguage{english}g*kg\textsuperscript{--1}*h\textsuperscript{--1}. Dosing seems to vary
inter-individually, especially in paediatrics, as shown by variable
half-life and clearance.\textsuperscript{26} Furthermore, the dosing
regimen depends on the route of administration. For nasal
administration, a 2 \selectlanguage{greek}μ\selectlanguage{english}g*kg\textsuperscript{--1} dose was the most
commonly used premedication dose in the present study. Therefore,
various dosing regimens should be available for physicians to use.

Bradycardia and hypotension were the most frequently reported side
effects of dexmedetomidine. Generally, these side effects do not require
additional treatment.\textsuperscript{15} Interestingly, only SPA
respondents reported an adverse drug reaction, nausea. A meta-analysis
has shown that dexmedetomidine prevents postoperative nausea and
vomiting in children and in adults when administered during general
anesthesia.\textsuperscript{27} The SPA respondents mostly use
dexmedetomidine in patients younger than 1 year of age, and respondents
from the other societies mostly in patients above 1 year of age, which
might explain the difference in reported adverse drug
reactions.\textsuperscript{28}

Dexmedetomidine is not the only anaesthetic drug used off-label in
paediatric anaesthesiology. Other studies have found that most drugs
administered to induce and to maintain anaesthesia are
off-label.\textsuperscript{29} Our study confirmed that dexmedetomidine
is used in infants, the age group with the least number of drugs
licenced for use.\textsuperscript{30} In a previous study, patients
treated with off-label drugs had a significantly higher risk of adverse
drug reactions.\textsuperscript{31} As we should not expose children to
unnecessary risks, it is important to investigate the pharmacokinetics
and pharmacodynamics of new drugs in clinical trials in the paediatric
population.\textsuperscript{32} In the absence of trials, formal
education for those prescribing and administering dexmedetomidine to
children would be necessary.

Our survey revealed various barriers to the use of dexmedetomidine in
paediatric practice. The main barriers were the price of
dexmedetomidine, non-availability of the drug, the lack of knowledge,
and the lack of education. Introduction of new drugs or adjusted use of
drugs in anaesthesia rarely comes with education of the
anesthesiologists.\textsuperscript{33} However, bed-side teaching of an
anaesthesiologist with experience (local opinion leader) in use of
dexmedetomidine during anaesthesia could counteract this barrier,
because this is an intervention for successful
implementation\textsuperscript{34,35} Unfortunately, our survey did not
investigate the reason why the lack of training has such a negative
effect on the use of dexmedetomidine, specifically. Mainly respondents
from the APAGBI reported not to have access to dexmedetomidine, which
explains the low use amongst APAGBI members. This might be due to the
fact that dexmedetomidine has not been licensed for anaesthesia in the
UK.\textsuperscript{36,37} Another reason why respondents do not use
dexmedetomidine is that they lack information about the drug. Long-term
effects on the use of dexmedetomidine in children have not yet been
published no studies have been published on the. Studies have focussed
on the short-term effects, such as safety of administration, emergence
delirium, postoperative nausea and
vomiting.\textsuperscript{38}Dexmedetomidine pharmacodynamics and
pharmacokinetics have mainly been described for adult
populations.\textsuperscript{15}

The use of dexmedetomidine amongst respondents from different societies
clearly differed with regard to patient age categories, routes of
administration, bodyweight-based dosages, dosing regimens and the
availability of protocols. We argue that paediatric anaesthesiologists
from different societies must learn from the others' experiences, share
information, and ultimately reach consensus on the optimal
dexmedetomidine therapy in paediatric anaesthesia. Such consensus might
stimulate good use. Consensus could be reached by evidence, expert
interpretation and experience. This consensus would lead to fewer
differences in drug prescriptions amongst hospitals, leading to improved
patient safety.\textsuperscript{39} This consensus should also include
adverse drug reactions and provide an option to report experienced
adverse drug events for pharmacovigilance.

We hypothesise that the unproven neurotoxicity of currently used
anaesthetics reduces the need for introduction of new drugs. The lack of
evidence on the advantages of dexmedetomidine does not provide a reason
to change current practice by introducing a new off-label drug with
unknown short-term and long-term risks.

Although we reached out to four major societies and associations for
paediatric anaesthesiologists, we could not reach all paediatric
anaesthesiologists because not everybody is a member of one of these
societies. We probably missed a large proportion, primarily those
working in Asia, Africa and South America.\textsuperscript{40} E-mails
with a link to the survey were sent out by the societies themselves, on
different dates after July 16\textsuperscript{th}, 2019. The closing
date was the same for all societies: August 16\textsuperscript{th}. The
different time windows to respond to the survey could have led to
response bias. We acknowledge the responder and non-responder bias for
this survey, which could have influenced the results. Those who do not
use dexmedetomidine in paediatrics might have been less likely to
participate, since they do not have any benefits from participation in
the study. The target response rate was set on 25\%, based on the
anaesthesiologists' heavy workload. The total number of
anaesthesiologists approached could be an overestimation because some
anaesthesiologists may a member of multiple societies, which could be an
explanation of the low response rate. Furthermore, except for ESPA
members, we do not know how many anaesthesiologists actually read the
e-mailed invitation and did not respond, or how many anaesthesiologists
missed the e-mail because it was relegated to the ``spam'' folder.
Furthermore, since physicians receive at least one survey daily, it is
not likely that they participate in every survey.\textsuperscript{41}

The majority of respondents in this survey use dexmedetomidine in
paediatric anaesthesia, despite its off-label status and the lack of
protocols. Dexmedetomidine provides sedation with minimal respiratory
depression and quick onset mechanism. Furthermore, it quickly wears off,
augments analgesia and is associated with only mild adverse drug
reactions that rarely require treatment. Intercontinental sharing of
experience and information would be desirable. Due to the off-label use
and lack of evidence on dexmedetomidine in children, a consensus amongst
experts on the use of this promising drug is decisive for the future
use. Peer-reviewed protocols, dosage recommendations and teaching
opportunities would be helpful in sharing the promising properties and
safety of dexmedetomidine in paediatric care.

Acknowledgments: We thank Ko Hagoort of the Erasmus MC-Sophia Children's
Hospital, Rotterdam for his editorial assistance.

Conflict of interest: none

Funding: not applicable

Data availability statement: The data that supports the findings of this
study are available in the article and the supplementary material of
this article

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Table 1. Baseline characteristics of all respondents\selectlanguage{english}
\begin{longtable}[]{@{}lllllllllll@{}}
\toprule
& \textbf{Total} & \textbf{Total} & \textbf{ESPA} & \textbf{ESPA} &
\textbf{SPANZA} & \textbf{SPANZA} & \textbf{APAGBI} & \textbf{APAGBI} &
\textbf{SPA} & \textbf{SPA}\tabularnewline
\midrule
\endhead
Member & & 5171 & & 849 & & 320 & & 872 & & 3130\tabularnewline
Response rate & 791 & 15.3\% & 229 & 27.0\% & 111 & 34.7\% & 129 &
14.8\% & 322 & 10.3\%\tabularnewline
\textbf{Do you use dexmedetomidine in paediatric anaesthesiology?} &
\textbf{Do you use dexmedetomidine in paediatric anaesthesiology?} &
\textbf{Do you use dexmedetomidine in paediatric anaesthesiology?} &
\textbf{Do you use dexmedetomidine in paediatric anaesthesiology?} &
\textbf{Do you use dexmedetomidine in paediatric anaesthesiology?} &
\textbf{Do you use dexmedetomidine in paediatric anaesthesiology?} &
\textbf{Do you use dexmedetomidine in paediatric anaesthesiology?} &
\textbf{Do you use dexmedetomidine in paediatric anaesthesiology?} &
\textbf{Do you use dexmedetomidine in paediatric anaesthesiology?} &
\textbf{Do you use dexmedetomidine in paediatric anaesthesiology?} &
\textbf{Do you use dexmedetomidine in paediatric
anaesthesiology?}\tabularnewline
Yes & 552 & 69.8\% & 121 & 52.8\% & 77 & 69.4\% & 44 & 34.1\% & 310 &
96.3\%\tabularnewline
No & 206 & 26.0\% & 90 & 39.3\% & 32 & 28.8\% & 80 & 62.0\% & 4 &
1.2\%\tabularnewline
Missing & 33 & 4.2\% & 18 & 7.9\% & 2 & 1.8\% & 5 & 3.9\% & 8 &
2.5\%\tabularnewline
Total & 791 & 100.0\% & 229 & 100.0\% & 111 & 100.0\% & 129 & 100.0\% &
322 & 100.0\%\tabularnewline
\textbf{What type of hospital do you work at?} & \textbf{What type of
hospital do you work at?} & \textbf{What type of hospital do you work
at?} & \textbf{What type of hospital do you work at?} & \textbf{What
type of hospital do you work at?} & \textbf{What type of hospital do you
work at?} & \textbf{What type of hospital do you work at?} &
\textbf{What type of hospital do you work at?} & \textbf{What type of
hospital do you work at?} & \textbf{What type of hospital do you work
at?} & \textbf{What type of hospital do you work at?}\tabularnewline
Tertiary & 558 & 70.5\% & 152 & 66.4\% & 91 & 82.0\% & 93 & 72.1\% & 222
& 68.9\%\tabularnewline
Paediatric & 116 & 14.7\% & 22 & 9.6\% & 4 & 3.6\% & 13 & 10.1\% & 77 &
23.9\%\tabularnewline
Secondary & 87 & 11.0\% & 38 & 16.6\% & 12 & 10.8\% & 18 & 14.0\% & 19 &
5.9\%\tabularnewline
Primary & 21 & 2.7\% & 10 & 4.4\% & 4 & 3.6\% & 4 & 3.1\% & 3 &
0.9\%\tabularnewline
Missing & 9 & 1.1\% & 7 & 3.1\% & 0 & 0.0\% & 1 & 0.8\% & 1 &
0.3\%\tabularnewline
Total & 791 & 100.0\% & 229 & 100.0\% & 111 & 100.0\% & 129 & 100.0\% &
322 & 100.0\%\tabularnewline
\textbf{What percentage of your work includes paediatric
anaesthesiology?} & \textbf{What percentage of your work includes
paediatric anaesthesiology?} & \textbf{What percentage of your work
includes paediatric anaesthesiology?} & \textbf{What percentage of your
work includes paediatric anaesthesiology?} & \textbf{What percentage of
your work includes paediatric anaesthesiology?} & \textbf{What
percentage of your work includes paediatric anaesthesiology?} &
\textbf{What percentage of your work includes paediatric
anaesthesiology?} & \textbf{What percentage of your work includes
paediatric anaesthesiology?} & \textbf{What percentage of your work
includes paediatric anaesthesiology?} & \textbf{What percentage of your
work includes paediatric anaesthesiology?} & \textbf{What percentage of
your work includes paediatric anaesthesiology?}\tabularnewline
10\% & 44 & 5.6\% & 23 & 10.0\% & 8 & 7.2\% & 8 & 6.2\% & 5 &
1.6\%\tabularnewline
25\% & 74 & 9.4\% & 25 & 10.9\% & 14 & 12.6\% & 11 & 8.5\% & 24 &
7.5\%\tabularnewline
50\% & 88 & 11.1\% & 37 & 16.2\% & 11 & 9.9\% & 5 & 3.9\% & 35 &
10.9\%\tabularnewline
75\% & 169 & 21.4\% & 45 & 19.7\% & 41 & 36.9\% & 40 & 31.0\% & 43 &
13.4\%\tabularnewline
100\% & 402 & 50.8\% & 90 & 39.3\% & 36 & 32.4\% & 63 & 48.8\% & 213 &
66.1\%\tabularnewline
Missing & 14 & 1.8\% & 9 & 3.9\% & 1 & 0.9\% & 2 & 1.6\% & 2 &
0.6\%\tabularnewline
Total & 791 & 100.0\% & 229 & 100.0\% & 111 & 100.0\% & 129 & 100.0\% &
322 & 100.0\%\tabularnewline
\textbf{What type of anaesthesiologist are you?} & \textbf{What type of
anaesthesiologist are you?} & \textbf{What type of anaesthesiologist are
you?} & \textbf{What type of anaesthesiologist are you?} & \textbf{What
type of anaesthesiologist are you?} & \textbf{What type of
anaesthesiologist are you?} & \textbf{What type of anaesthesiologist are
you?} & \textbf{What type of anaesthesiologist are you?} & \textbf{What
type of anaesthesiologist are you?} & \textbf{What type of
anaesthesiologist are you?} & \textbf{What type of anaesthesiologist are
you?}\tabularnewline
Paediatric & 693 & 87.6\% & 182 & 79.5\% & 97 & 87.4\% & 112 & 86.8\% &
302 & 93.8\%\tabularnewline
Ped training & 29 & 3.7\% & 11 & 4.8\% & 5 & 4.5\% & 5 & 3.9\% & 8 &
2.5\%\tabularnewline
General & 43 & 5.4\% & 23 & 10.0\% & 8 & 7.2\% & 7 & 5.4\% & 5 &
1.6\%\tabularnewline
Resident & 7 & 0.9\% & 3 & 1.3\% & 0 & 0.0\% & 1 & 0.8\% & 3 &
0.9\%\tabularnewline
Missing & 19 & 2.4\% & 10 & 4.4\% & 1 & 0.9\% & 4 & 3.1\% & 4 &
1.2\%\tabularnewline
Total & 791 & 100.0\% & 229 & 100.0\% & 111 & 100.0\% & 129 & 100.0\% &
322 & 100.0\%\tabularnewline
\bottomrule
\end{longtable}

Table 2. Dexmedetomidine dosages reported by respondents (median with
interquartile ranges, minimum and maximum dose).\selectlanguage{english}
\begin{longtable}[]{@{}lllllllll@{}}
\toprule
\begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
\textbf{Setting}\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
\textbf{Bolus min} \textbf{ug*kg\textsuperscript{-1}}\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
\textbf{Bolus min} \textbf{ug*kg\textsuperscript{-1}}\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
\textbf{Bolus max} \textbf{ug*kg\textsuperscript{-1}}\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
\textbf{Bolus max} \textbf{ug*kg\textsuperscript{-1}}\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
\textbf{IV min} \textbf{mg*kg/h\textsuperscript{-1}}\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
\textbf{IV min} \textbf{mg*kg/h\textsuperscript{-1}}\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
\textbf{IV max} \textbf{mg*kg/h\textsuperscript{-1}}\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
\textbf{IV max} \textbf{mg*kg/h\textsuperscript{-1}}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Premedication} (nasal)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2.00 {[}1.00-2.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2.00 {[}1.00-2.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2.00 {[}2.00-3.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2.00 {[}2.00-3.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1.50 {[}0.50-4.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1.50 {[}0.50-4.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2.50 {[}1.00-4.25{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2.50 {[}1.00-4.25{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Min - max\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
5.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.20\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
5.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.25\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
5.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.50\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
5.00\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Procedural sedation}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.00 {[}0.50-2.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.00 {[}0.50-2.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.10 {[}1.00-2.38{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.10 {[}1.00-2.38{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.50 {[}0.30-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.50 {[}0.30-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
{[}0.70-1.75{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
{[}0.70-1.75{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Min - max\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
8.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.20\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
8.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2.50\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.20\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
6.00\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Intensive care sedation}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.00 {[}0.50-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.00 {[}0.50-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
{[}0.50-1.05{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
{[}0.50-1.05{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.50 {[}0.30-0.70{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.50 {[}0.30-0.70{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
{[}0.70-1.50{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
{[}0.70-1.50{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Min - max\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.50\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
8.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.50\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
8.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
5.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.10\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
7.00\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Anaesthesia}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.50 {[}0.50-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.50 {[}0.50-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1.00 {[}0.50-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1.00 {[}0.50-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.50 {[}0.30-0.70{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.50 {[}0.30-0.70{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1.00 {[}0.50-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1.00 {[}0.50-1.00{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Min - max\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
4.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
5.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.03\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
4.00\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Postoperative analgesia}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.50 {[}0.40-0.50{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.50 {[}0.40-0.50{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.50 {[}0.50-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.50 {[}0.50-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.40 {[}0.20-0.50{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.40 {[}0.20-0.50{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.50 {[}0.43-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.50 {[}0.43-1.00{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Min - max\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.20\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
3.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.10\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2.00\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Other}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.50 {[}0.30-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.50 {[}0.30-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.85 {[}0.50-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.85 {[}0.50-1.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.90 {[}0.50-1.75{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.90 {[}0.50-1.75{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
{[}0.78-2.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
{[}0.78-2.00{]}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Min - max\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.10\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.20\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
5.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.10\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
2.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
0.60\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
3.00\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Median {[}IQR{]} and minimum and maximum (min -- max) dosage
administered.

Lowest and highest reported doses for bolus and continuous infusion of
dexmedetomidine.

All settings, except for premedication, was mainly administered
intravenously.

Table 3. Responses of respondents who use dexmedetomidine\selectlanguage{english}
\begin{longtable}[]{@{}lllllllllll@{}}
\toprule
& \textbf{Total} & \textbf{Total} & \textbf{ESPA} & \textbf{ESPA} &
\textbf{SPANZA} & \textbf{SPANZA} & \textbf{APAGBI} & \textbf{APAGBI} &
\textbf{SPA} & \textbf{SPA}\tabularnewline
\midrule
\endhead
& \textbf{552} & \textbf{552} & \textbf{121} & \textbf{121} &
\textbf{77} & \textbf{77} & \textbf{44} & \textbf{44} & \textbf{310} &
\textbf{310}\tabularnewline
\textbf{Is there a protocol available in your centre?} & \textbf{Is
there a protocol available in your centre?} & \textbf{Is there a
protocol available in your centre?} & \textbf{Is there a protocol
available in your centre?} & \textbf{Is there a protocol available in
your centre?} & \textbf{Is there a protocol available in your centre?} &
\textbf{Is there a protocol available in your centre?} & \textbf{Is
there a protocol available in your centre?} & \textbf{Is there a
protocol available in your centre?} & \textbf{Is there a protocol
available in your centre?} & \textbf{Is there a protocol available in
your centre?}\tabularnewline
Yes. a protocol is available & 402 & 72.8\% & 57 & 47.1\% & 33 & 42.9\%
& 27 & 61.4\% & 285 & 91.9\%\tabularnewline
No. no protocol is available & 102 & 18.5\% & 47 & 38.8\% & 37 & 48.1\%
& 11 & 25.0\% & 7 & 2.3\%\tabularnewline
Missing & 48 & 8.7\% & 17 & 14.0\% & 7 & 9.1\% & 6 & 13.6\% & 18 &
5.8\%\tabularnewline
Total & 552 & 100.0\% & 121 & 100.0\% & 77 & 100.0\% & 44 & 100.0\% &
310 & 100.0\%\tabularnewline
\textbf{In what age categories do you use dexmedetomidine?*} &
\textbf{In what age categories do you use dexmedetomidine?*} &
\textbf{In what age categories do you use dexmedetomidine?*} &
\textbf{In what age categories do you use dexmedetomidine?*} &
\textbf{In what age categories do you use dexmedetomidine?*} &
\textbf{In what age categories do you use dexmedetomidine?*} &
\textbf{In what age categories do you use dexmedetomidine?*} &
\textbf{In what age categories do you use dexmedetomidine?*} &
\textbf{In what age categories do you use dexmedetomidine?*} &
\textbf{In what age categories do you use dexmedetomidine?*} &
\textbf{In what age categories do you use
dexmedetomidine?*}\tabularnewline
- 0-3 months old & 363 & 65.8\% & 50 & 41.3\% & 23 & 29.9\% & 6 & 13.6\%
& 284 & 91.6\%\tabularnewline
- 3 months to 1 year & 404 & 73.2\% & 76 & 62.8\% & 37 & 48.1\% & 17 &
38.6\% & 274 & 88.4\%\tabularnewline
- 1 to 4 years & 330 & 59.8\% & 100 & 82.6\% & 63 & 81.8\% & 34 & 77.3\%
& 133 & 42.9\%\tabularnewline
- 4 to 6 years & 291 & 52.7\% & 102 & 84.3\% & 73 & 94.8\% & 38 & 86.4\%
& 78 & 25.2\%\tabularnewline
- 6 to 12 years & 388 & 70.3\% & 87 & 71.9\% & 70 & 90.9\% & 35 & 79.5\%
& 196 & 63.2\%\tabularnewline
- older than 12 years & 256 & 46.4\% & 75 & 62.0\% & 63 & 81.8\% & 33 &
75.0\% & 85 & 27.4\%\tabularnewline
\textbf{For what purposes do you use dexmedetomidine?*} & \textbf{For
what purposes do you use dexmedetomidine?*} & \textbf{For what purposes
do you use dexmedetomidine?*} & \textbf{For what purposes do you use
dexmedetomidine?*} & \textbf{For what purposes do you use
dexmedetomidine?*} & \textbf{For what purposes do you use
dexmedetomidine?*} & \textbf{For what purposes do you use
dexmedetomidine?*} & \textbf{For what purposes do you use
dexmedetomidine?*} & \textbf{For what purposes do you use
dexmedetomidine?*} & \textbf{For what purposes do you use
dexmedetomidine?*} & \textbf{For what purposes do you use
dexmedetomidine?*}\tabularnewline
For premedication & 255 & 46.2\% & 57 & 47.1\% & 62 & 80.5\% & 30 &
68.2\% & 106 & 34.2\%\tabularnewline
For procedural sedation & 375 & 67.9\% & 78 & 64.5\% & 34 & 44.2\% & 10
& 22.7\% & 253 & 81.6\%\tabularnewline
For IC sedation & 251 & 45.5\% & 65 & 53.7\% & 17 & 22.1\% & 10 & 22.7\%
& 159 & 51.3\%\tabularnewline
For anaesthesia & 93 & 16.8\% & 31 & 25.6\% & 40 & 51.9\% & 13 & 29.5\%
& 9 & 2.9\%\tabularnewline
For postoperative analgesia & 178 & 32.2\% & 27 & 22.3\% & 11 & 14.3\% &
6 & 13.6\% & 134 & 43.2\%\tabularnewline
\textbf{What adverse drug reactions have you
experienced?\textsuperscript{a}} & \textbf{What adverse drug reactions
have you experienced?\textsuperscript{a}} & \textbf{What adverse drug
reactions have you experienced?\textsuperscript{a}} & \textbf{What
adverse drug reactions have you experienced?\textsuperscript{a}} &
\textbf{What adverse drug reactions have you
experienced?\textsuperscript{a}} & \textbf{What adverse drug reactions
have you experienced?\textsuperscript{a}} & \textbf{What adverse drug
reactions have you experienced?\textsuperscript{a}} & \textbf{What
adverse drug reactions have you experienced?\textsuperscript{a}} &
\textbf{What adverse drug reactions have you
experienced?\textsuperscript{a}} & \textbf{What adverse drug reactions
have you experienced?\textsuperscript{a}} & \textbf{What adverse drug
reactions have you experienced?\textsuperscript{a}}\tabularnewline
Hypotension & 78 & 14.1\% & 46 & 38.0\% & 19 & 24.7\% & 6 & 13.6\% & 7 &
2.3\%\tabularnewline
Hypertension & 20 & 3.6\% & 16 & 13.2\% & 1 & 1.3\% & 1 & 2.3\% & 2 &
0.6\%\tabularnewline
Bradycardia & 129 & 23.4\% & 74 & 61.2\% & 29 & 37.7\% & 11 & 25.0\% &
15 & 4.8\%\tabularnewline
Hypoxia & 55 & 10.0\% & 2 & 1.7\% & 0 & 0.0\% & 0 & 0.0\% & 53 &
17.1\%\tabularnewline
Apnoea & 9 & 1.6\% & 6 & 5.0\% & 1 & 1.3\% & 1 & 2.3\% & 1 &
0.3\%\tabularnewline
Nausea & 99 & 17.9\% & 0 & 0.0\% & 0 & 0.0\% & 0 & 0.0\% & 99 &
31.9\%\tabularnewline
Emergence delirium & 16 & 2.9\% & 13 & 10.7\% & 3 & 3.9\% & 0 & 0.0\% &
0 & 0.0\%\tabularnewline
None & 275 & 49.8\% & 27 & 22.3\% & 36 & 46.8\% & 22 & 50.0\% & 190 &
61.3\%\tabularnewline
\textbf{Are you familiar with any contraindications for the use of
dexmedetomidine?} & \textbf{Are you familiar with any contraindications
for the use of dexmedetomidine?} & \textbf{Are you familiar with any
contraindications for the use of dexmedetomidine?} & \textbf{Are you
familiar with any contraindications for the use of dexmedetomidine?} &
\textbf{Are you familiar with any contraindications for the use of
dexmedetomidine?} & \textbf{Are you familiar with any contraindications
for the use of dexmedetomidine?} & \textbf{Are you familiar with any
contraindications for the use of dexmedetomidine?} & \textbf{Are you
familiar with any contraindications for the use of dexmedetomidine?} &
\textbf{Are you familiar with any contraindications for the use of
dexmedetomidine?} & \textbf{Are you familiar with any contraindications
for the use of dexmedetomidine?} & \textbf{Are you familiar with any
contraindications for the use of dexmedetomidine?}\tabularnewline
Yes. I am familiar with contraindications & 170 & 30.8\% & 88 & 72.7\% &
52 & 67.5\% & 23 & 52.3\% & 7 & 2.3\%\tabularnewline
No. I am not familiar with contraindications & 350 & 63.4\% & 25 &
20.7\% & 22 & 28.6\% & 17 & 38.6\% & 286 & 92.3\%\tabularnewline
Missing & 32 & 5.8\% & 8 & 6.6\% & 3 & 3.9\% & 4 & 9.1\% & 17 &
5.5\%\tabularnewline
Total & 552 & 100.0\% & 33 & 100.0\% & 25 & 100.0\% & 21 & 100.0\% & 303
& 100.0\%\tabularnewline
\textbf{How would you rate your experience with dexmedetomidine? Median
{[}IQR{]}} & \textbf{How would you rate your experience with
dexmedetomidine? Median {[}IQR{]}} & \textbf{How would you rate your
experience with dexmedetomidine? Median {[}IQR{]}} & \textbf{How would
you rate your experience with dexmedetomidine? Median {[}IQR{]}} &
\textbf{How would you rate your experience with dexmedetomidine? Median
{[}IQR{]}} & \textbf{How would you rate your experience with
dexmedetomidine? Median {[}IQR{]}} & \textbf{How would you rate your
experience with dexmedetomidine? Median {[}IQR{]}} & \textbf{How would
you rate your experience with dexmedetomidine? Median {[}IQR{]}} &
\textbf{How would you rate your experience with dexmedetomidine? Median
{[}IQR{]}} & \textbf{How would you rate your experience with
dexmedetomidine? Median {[}IQR{]}} & \textbf{How would you rate your
experience with dexmedetomidine? Median {[}IQR{]}}\tabularnewline
& & & 8 {[}7-9{]} & 8 {[}7-9{]} & 8 {[}7-8{]} & 8 {[}7-8{]} & 8
{[}7-8{]} & 8 {[}7-8{]} & 10 {[}9-10{]} & 10 {[}9-10{]}\tabularnewline
\bottomrule
\end{longtable}

\textsuperscript{a}multiple answers possible

Table 4. Responses of respondents who do not use dexmedetomidine\selectlanguage{english}
\begin{longtable}[]{@{}lllllllllll@{}}
\toprule
& \textbf{Total 206} & \textbf{Total 206} & \textbf{ESPA 90} &
\textbf{ESPA 90} & \textbf{SPANZA 32} & \textbf{SPANZA 32} &
\textbf{APAGBI 80} & \textbf{APAGBI 80} & \textbf{SPA 4} & \textbf{SPA
4}\tabularnewline
\midrule
\endhead
\textbf{Are you trained in the use of dexmedetomidine?} & \textbf{Are
you trained in the use of dexmedetomidine?} & \textbf{Are you trained in
the use of dexmedetomidine?} & \textbf{Are you trained in the use of
dexmedetomidine?} & \textbf{Are you trained in the use of
dexmedetomidine?} & \textbf{Are you trained in the use of
dexmedetomidine?} & \textbf{Are you trained in the use of
dexmedetomidine?} & \textbf{Are you trained in the use of
dexmedetomidine?} & \textbf{Are you trained in the use of
dexmedetomidine?} & \textbf{Are you trained in the use of
dexmedetomidine?} & \textbf{Are you trained in the use of
dexmedetomidine?}\tabularnewline
Yes & 23 & 11.2\% & 8 & 8.9\% & 4 & 12.5\% & 9 & 11.3\% & 2 &
50.0\%\tabularnewline
No & 182 & 88.3\% & 81 & 90.0\% & 28 & 87.5\% & 71 & 88.8\% & 2 &
50.0\%\tabularnewline
Missing & 1 & 0.5\% & 1 & 1.1\% & 0 & 0.0\% & 0 & 0.0\% & 0 &
0.0\%\tabularnewline
Total & 206 & 100.0\% & 90 & 100.0\% & 32 & 100.0\% & 80 & 100.0\% & 4 &
100.0\%\tabularnewline
\textbf{Are you familiar with dexmedetomidine?} & \textbf{Are you
familiar with dexmedetomidine?} & \textbf{Are you familiar with
dexmedetomidine?} & \textbf{Are you familiar with dexmedetomidine?} &
\textbf{Are you familiar with dexmedetomidine?} & \textbf{Are you
familiar with dexmedetomidine?} & \textbf{Are you familiar with
dexmedetomidine?} & \textbf{Are you familiar with dexmedetomidine?} &
\textbf{Are you familiar with dexmedetomidine?} & \textbf{Are you
familiar with dexmedetomidine?} & \textbf{Are you familiar with
dexmedetomidine?}\tabularnewline
Yes & 89 & 48.9\% & 43 & 53.1\% & 18 & 64.3\% & 26 & 36.6\% & 2 &
100.0\%\tabularnewline
No & 90 & 49.5\% & 37 & 45.7\% & 10 & 35.7\% & 43 & 60.6\% & 0 &
0.0\%\tabularnewline
Missing & 3 & 1.6\% & 1 & 1.2\% & 0 & 0.0\% & 2 & 2.8\% & 0 &
0.0\%\tabularnewline
Total & 182 & 100.0\% & 81 & 100.0\% & 28 & 100.0\% & 71 & 100.0\% & 2 &
100.0\%\tabularnewline
\textbf{Are you willing to start using
dexmedetomidine?\textsuperscript{a}} & \textbf{Are you willing to start
using dexmedetomidine?\textsuperscript{a}} & \textbf{Are you willing to
start using dexmedetomidine?\textsuperscript{a}} & \textbf{Are you
willing to start using dexmedetomidine?\textsuperscript{a}} &
\textbf{Are you willing to start using
dexmedetomidine?\textsuperscript{a}} & \textbf{Are you willing to start
using dexmedetomidine?\textsuperscript{a}} & \textbf{Are you willing to
start using dexmedetomidine?\textsuperscript{a}} & \textbf{Are you
willing to start using dexmedetomidine?\textsuperscript{a}} &
\textbf{Are you willing to start using
dexmedetomidine?\textsuperscript{a}} & \textbf{Are you willing to start
using dexmedetomidine?\textsuperscript{a}} & \textbf{Are you willing to
start using dexmedetomidine?\textsuperscript{a}}\tabularnewline
Yes. I am willing to start using & 174 & 84.5\% & 77 & 85.6\% & 29 &
90.6\% & 66 & 82.5\% & 2 & 50.0\%\tabularnewline
Yes: good alternative & 38 & 21.8\% & 14 & 15.6\% & 8 & 25.0\% & 16 &
20.0\% & 0 & 0.0\%\tabularnewline
Yes: benefits of the drug & 82 & 47.1\% & 31 & 34.4\% & 13 & 40.6\% & 36
& 45.0\% & 2 & 50.0\%\tabularnewline
Yes: literature information & 4 & 2.3\% & 3 & 3.3\% & 0 & 0.0\% & 1 &
1.3\% & 0 & 0.0\%\tabularnewline
Yes: if recommended & 3 & 1.7\% & 2 & 2.2\% & 0 & 0.0\% & 1 & 1.3\% & 0
& 0.0\%\tabularnewline
Yes: if more information is available & 7 & 4.0\% & 3 & 3.3\% & 1 &
3.1\% & 3 & 3.8\% & 0 & 0.0\%\tabularnewline
Yes: other & 40 & 23.0\% & 24 & 26.7\% & 7 & 21.9\% & 9 & 11.3\% & 0 &
0.0\%\tabularnewline
Total & 174 & & 77 & & 29 & & 66 & & 2 & 50.0\%\tabularnewline
No. I am not willing to start using & 29 & 14.1\% & 12 & 13.3\% & 3 &
9.4\% & 12 & 15.0\% & 2 & 50.0\%\tabularnewline
No: better alternative & 7 & 24.1\% & 5 & 5.6\% & 0 & 0.0\% & 1 & 1.3\%
& 1 & 25.0\%\tabularnewline
No: not registrated in country & 4 & 13.8\% & 1 & 1.1\% & 1 & 3.1\% & 2
& 2.5\% & 0 & 0.0\%\tabularnewline
No: no protocols & 0 & 0.0\% & 0 & 0.0\% & 0 & 0.0\% & 0 & 0.0\% & 0 &
0.0\%\tabularnewline
No: no need & 9 & 31.0\% & 3 & 3.3\% & 2 & 6.3\% & 3 & 3.8\% & 1 &
25.0\%\tabularnewline
No: price & 1 & 3.4\% & 1 & 1.1\% & 0 & 0.0\% & 0 & 0.0\% & 0 &
0.0\%\tabularnewline
No: more experience needed & 7 & 24.1\% & 2 & 2.2\% & 0 & 0.0\% & 5 &
6.3\% & 0 & 0.0\%\tabularnewline
No: other & 1 & 3.4\% & 0 & 0.0\% & 0 & 0.0\% & 1 & 1.3\% & 0 &
0.0\%\tabularnewline
Total & 29 & 100.0\% & 12 & 98.9\% & 3 & 100.0\% & 12 & 97.5\% & 10 &
100.0\%\tabularnewline
\textbf{For what purposes would you use
dexmedetomidine?\textsuperscript{a}} & \textbf{For what purposes would
you use dexmedetomidine?\textsuperscript{a}} & \textbf{For what purposes
would you use dexmedetomidine?\textsuperscript{a}} & \textbf{For what
purposes would you use dexmedetomidine?\textsuperscript{a}} &
\textbf{For what purposes would you use
dexmedetomidine?\textsuperscript{a}} & \textbf{For what purposes would
you use dexmedetomidine?\textsuperscript{a}} & \textbf{For what purposes
would you use dexmedetomidine?\textsuperscript{a}} & \textbf{For what
purposes would you use dexmedetomidine?\textsuperscript{a}} &
\textbf{For what purposes would you use
dexmedetomidine?\textsuperscript{a}} & \textbf{For what purposes would
you use dexmedetomidine?\textsuperscript{a}} & \textbf{For what purposes
would you use dexmedetomidine?\textsuperscript{a}}\tabularnewline
For premedication & 126 & 72.4\% & 42 & 54.5\% & 26 & 89.7\% & 58 &
87.9\% & 0 & 0.0\%\tabularnewline
For procedural sedation & 133 & 76.4\% & 65 & 84.4\% & 20 & 69.0\% & 48
& 72.7\% & 0 & 0.0\%\tabularnewline
For IC sedation & 58 & 33.3\% & 34 & 44.2\% & 7 & 24.1\% & 17 & 25.8\% &
0 & 0.0\%\tabularnewline
For anaesthesia & 75 & 43.1\% & 27 & 35.1\% & 11 & 37.9\% & 37 & 56.1\%
& 0 & 0.0\%\tabularnewline
For postoperative analgesia & 48 & 27.6\% & 18 & 23.4\% & 8 & 27.6\% &
22 & 33.3\% & 0 & 0.0\%\tabularnewline
Missing & 1 & 0.6\% & 0 & 0.0\% & 0 & 0.0\% & 0 & 0.0\% & 1 &
50.0\%\tabularnewline
Other & 8 & 4.6\% & 4 & 5.2\% & 2 & 6.9\% & 1 & 1.5\% & 1 &
50.0\%\tabularnewline
\bottomrule
\end{longtable}

\textsuperscript{a}multiple answers possible

\section*{Figure legends}

{\label{figure-legends}}

Figure 1. Distribution and response diagram of the survey

Figure 2. Reasons why respondents started using dexmedetomidine

Multiple answers possible

Figure 3. Reasons why respondents do not use dexmedetomidine

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