Intravenous Sedation for
Endoscopy in a Developing Country
Department of Anesthesiology and Siriraj GI Endoscopy Center, Faculty of Medicine,
Siriraj Hospital, Mahidol University, Bangkok,
The field of pediatric sedation and analgesia has evolved over the past two decades. The
growing number of pediatric gastrointestinal endoscopy procedures requiring sedation and
analgesia are recognized even in developing countries. It is well accepted that children
undergoing diagnostic and therapeutic gastrointestinal endoscopic procedures should receive
sedation and/or anesthesia. Nevertheless, considerable practice variation prevails. The
ability to provide safe and effective sedation and analgesia is an important skill for physicians
involved in pediatric patients. Children are more prone to anxiety in the acute setting.
Procedural sedation and analgesia is the use of sedative, analgesic and dissociate drugs to
provide anxiolysis, analgesia, sedation and motor control during painful and unpleasant
Intravenous sedation for pediatric gastrointestinal endoscopic procedure is ubiquitous in
any hospital that cares for children and depending on the institution and country. The
developing countries have no their practice guidelines. The guidelines established by the
American Academy of Pediatrics (AAP) (Cote et al., 2006), the American Society of
Anesthesiologists (ASA, 2002) and the Joint Commission on Accreditation of Healthcare
Organizations (JCAHO) serve as the standard for institutional policy development in the
area of pediatric intravenous sedation.
The guideline defines terms throughout and in particular:
Minimal sedation: a drug-induced state which patients respond normally to verbal
Moderate sedation (conscious sedation): a drug-induced depression of consciousness which
patients respond purposefully to verbal commands. Spontaneous ventilation is adequate.
Cardiovascular function is usually maintained.
Deep sedation: a drug-induced depression of consciousness which patients can not be
easily aroused but respond purposefully after repeated verbal or painful stimulation.
Spontaneous ventilation may be inadequate. Cardiovascular function is usually
General anesthesia: a drug-induced loss of consciousness which patients are not
arousable, even by painful stimulation. Patients often require assistance in maintaining
a patent airway. Cardiovascular function may be impaired.
In this report, the author will seek to examine the role of anesthesiologists in determining
the field of pediatric intravenous sedation, and the current status of intravenous sedation for
pediatric gastrointestinal endoscopic procedures in Siriraj GI Endoscopy Center, Siriraj
Hospital, Thailand. Additionally, this review is divided into three parts: 1. the pre-pediatric
gastrointestinal endoscopic assessment period, 2. the intra-pediatric gastrointestinal
endoscopic management period, and 3. the post-pediatric gastrointestinal endoscopy period.
2. Pre-pediatric gastrointestinal endoscopic assessment period
The general health status of each patient undergoing pediatric procedural intravenous
sedation must be evaluated. A physical examination should focus primarily on the upper
airway, lungs, cardiovascular system, and baseline neurological status. To aid in assessment
risk, the American Society of Anesthesiologists (ASA) has developed a classification system
for patients, which categorizes individuals on a general health basis. Several studies have
documented the fact that sedation risk in children rises with increasing ASA physical status
(Cote et al., 2006; Krauss & Green, 2006; Vespasiano et al., 2007). ASA physical status 1 and 2
are considered low risk patient populations. ASA physical status 3 and 4 are high risk
patient populations. The specific high risk patient populations in which anesthesia
consultation may be warranted including known respiratory or hemodynamic instability,
obstructive sleep apnea, high risk airway management, ASA physical status ≥4, infants born
<37 weeks and <60 weeks post conception, history of sedation related adverse events, and
patients with neuromuscular disease affecting respiratory or brain stem function.
In this pre-assessment period, there are no differences in a routine practice between the
developed countries and the developing countries. Additionally, the majority of intravenous
sedation practices for pediatric gastrointestinal endoscopic procedures in the developing
countries were sedated by anesthesiologists and/or anesthetic personnel in the operating
3. Intra-pediatric gastrointestinal endoscopic management period
Any time sedative and analgesic medications are to be given to a pediatric patient, a clearly
worded informed consent should be obtained. This consent should include a listing of the
possible consequences of adverse drug reactions, allergic reactions and airway difficulties.
Prior to undertaking intravenous sedation, there are some key pieces of equipment that
must be in place. These equipments that should be in place before starting a sedation are
suction, oxygen, airway, pharmacy, monitors, and extra equipment such as defibrillator
(SOAPME) (Cote et al., 2006). In general, intravenous sedation for pediatric gastrointestinal
endoscopic procedures is done by anesthesiologists or anesthetic personnel directly
supervised by the anesthesiologist or anesthetic personnel.
In a developing country where pediatric endoscopy is performed at increasing rates, the
majority of cases (as noted by anecdotal observation) are treated under general anesthesia in
the operating room. At Siriraj Hospital, there is a dedicated endoscopy unit with dedicated
anesthesia service. Over the last four years, 2006–2010, we performed most pediatric
gastrointestinal endoscopic procedures with intravenous sedation technique. We followed
the guidelines provided by the American Academy of Pediatrics (Cote et al., 2006) and
American Society of Anesthesiologists standards (ASA, 2002). Our review of intravenous
sedation practice in pediatric population showed that intravenous sedation can be done
Intravenous Sedation for Pediatric Gastrointestinal Endoscopy in a Developing Country
safely with various sedative combinations with proper monitoring and anesthesiology
Patient monitoring during the procedure should be included continuous monitoring of heart
rate and oxygen saturation, and intermittent recording of respiratory rate and blood
pressure. Additionally, capnography detects increasing levels of carbon dioxide before
desaturation occurs and can detect early inadequately ventilation (Krauss & Green, 2000).
However, the cost of capnometer is relatively high. The developing countries like Thailand
have none or few capnometers, though this monitor is not routinely used. A sedative drug
can only be considered safe after experience in hundreds or thousands of cases. Good
protocols are important for the safety and success of the intravenous sedation technique.
Depending on the procedure, pediatric intravenous sedation can involve monotherapy or
combination therapy. Each regimen and administration of intravenous sedation must be
carefully personalized for each patient. When administered, the drugs should be given as an
appropriate initial dose with subsequent doses until titrated to effect. However, the most
important factor is the judgement of the physician (ASA, 2002; Sury, 2004; Cote et al., 2006;
Krauss & Green, 2006; Vespasiano et al., 2007; Meredith et al., 2008).
Common drug-receptor systems used by anesthesiologists in Thailand include the following:
Opioid receptors: fentanyl, meperidine
Gamma-aminobytyric acid (GABA) receptors: propofol
Benzodiazepine receptors: midazolam
N-methyl-D-aspartate (NMDA) receptors: ketamine
Sedation should be administered based on the patient’s weight and titrated by response.
Dosing requirements for individual patients may vary significantly based on the patient’s
psychosocial development and attention to the surrounding environment by the endoscopy
team. Adequate time should be allowed between doses to assess sedation effects and
determine the need for additional medication. For example, midazolam should be titrated to
the effect with at least three minutes between doses, while fentanyl should have five
minutes between doses. Higher doses of sedative/analgesic agents are frequently needed in
preschool, school aged and preteen patients compared with those used in teenage children.
The most common intravenous sedation regimen for pediatric gastrointestinal endoscopic
procedure is the use of an opioid and a benzodiazepine combination to achieve analgesia
and amnesia (Dar & Shah, 2010). Many safe regimens were reported. Consequently,
anesthesiologist or the anesthetic personnel must exercise extreme caution while administering
the intravenous sedation for pediatric gastrointestinal endoscopic procedure. The use of
intravenous sedation drugs is reliability, efficacy and easy titration to achieve the end point.
However, monitoring during the procedure is essential.
3.1 Analgesic drugs
Fentanyl is a potent synthetic opioid with no intrinsic anxiolytic or amnestic properties. It
has high lipid solubility allows for quick penetration of the blood-brain barrier, resulting in
a very rapid onset of action (<1 minute) and short duration of action (30-45 minutes)
(Nowicki & Vaughn, 2002; Dar & Shah, 2010). Fentanyl lacks of direct of myocardial
depressant effects, and absence of histamine release, making it an excellent choice for
intravenous sedation. Intravenous fentanyl can be easily and rapidly titrated for painful
procedures (Kennedy et al., 1998; Pitetti et al., 2003). The combination of fentanyl and
midazolam is a popular intravenous sedation regimen, with a safety profile when both
drugs are carefully titrated (Kennedy et al., 1998; Pena & Krauss, 1999; Pitetti et al., 2003).
Fentanyl can cause respiratory depression and apnea, especially when combined with other
sedatives or in infants less than 3 months of age (C.L. Algren & C.T. Algren, 1997). Fentanyl-
induced bradycardia may need treatment with a vagolytic drug such as atropine. Chest wall
and glottic rigidity has been observed with rapid administration of fentanyl. Safe
intravenous administration therefore requires slow titration of 0.5-1.0 mcg/kg boluses, and
may repeat every 3 minutes, but the maximum cumulative dose is 4 to 5 mcg/kg in one
hour (Tolia et al., 2000).
3.1.2 Meperidine (Pethidine)
Meperidine is a synthetic opioid and has grown out of favor in past years. The metabolites
of meperidine are toxic to the central nervous system at high doses and in patients with
renal impairment. Meperidine has a long and favorable experience in intravenous sedation
for pediatric gastrointestinal endoscopic procedure (Bahal-O’Mara et al., 1993). Meperidine
0.5-1.0 mg/kg i.v. combined with midazolam 0.05-0.1 mg/kg i.v. provides effective sedation
for gastrointestinal endoscopy. However, meperidine is not recommended for intravenous
sedation in the emergency department (Lewis & Stanley, 1999; Mace, 2004). Side effects of
meperidine are respiratory depression, nausea, vomiting, and dysphoria (Goad & Webster,
1997). It causes less histamine release and urticaria than morphine (C.L. Algren & C.T. Algren,
1997). Fatal reactions have also occurred in patients taking monoamine oxidase inhibitors.
3.2 Sedative drugs
Propofol is a phenol derivative with sedative, hypnotic and anesthetic properties. It has a
rapid onset (< 1 minute), shorter duration of action, and rapid recovery. Its clinical effects
are dose dependent. Propofol has antiemetic, anxiolytic, hypnotic, amnestic and anesthetic
properties. However, it does not have analgesic effects. Propofol can be given to children in
the settings of gastroenterology (Barbi et al., 2003; Amornyotin et al., 2009, 2010), emergency
department (Bassett et al., 2003; Green & Krauss, 2003), and critical care series (Lowrie et al.,
1998) with good efficacy, rapid recovery, and apparent safety. The most serious adverse
effect of propofol is potent respiratory depression and apnea can occur suddenly. The
respiratory depression rates vary extensively by the study (Green & Krauss, 2003). Propofol
can also produce hypotension, although this effect is typically transient and of little clinical
importance in healthy patients (Green & Krauss, 2003). Propofol is well known to be painful
upon injection, the addition of lidocaine has been shown to decrease the incidence of pain
during injection (Bassett et al., 2003).
Currently, most centers utilize an anesthesiologist or nurse anesthetist to administer
propofol (Sury & Smith, 2008), although recently nurse administered and patient controlled
dosing has been reported in adult patients. In our endoscopy center, propofol is also
administered by an anesthesiologist or nurse anesthetist. Propofol provides equal or better
control and more rapid recovery when compared with midazolam for sedation (O’Hare et
al., 2001). Initial intravenous bolus dose of propofol is 1.0 mg/kg and is followed by 0.5
mg/kg, and the repeated dose is needed. In my experience, I use the initial bolus dose of
propofol and follow by the continuous intravenous technique. The continuous intravenous
infusion of propofol dose is 100-150 mcg/kg/min. Majority of our patients received
propofol in combination with other sedatives. Over the last decade, the use of propofol for
endoscopic sedation has increased. It has gained wide acceptance among adult
Intravenous Sedation for Pediatric Gastrointestinal Endoscopy in a Developing Country
gastroenterologist. The use of propofol in pediatric population has been shown to be safe,
effective, and reliable (Balsells et al., 1997; Kaddu et al., 2002). The drug, now commonly
used outside the operating room, has demonstrated an excellent safety profile, despite a
narrow therapeutic window. Desirable properties of propofol for endoscopic procedures
include ease of use, quick onset of action, and rapid metabolization leading to shorter
recovery time (Aouad M.T. et al., 2008).
Midazolam is the drug most commonly used for sedation in children during procedures
(Kennedy et al., 1998; Pena & Krauss, 1999). It is a shorting, water soluble benzodiazepine
with anxiolytic, amnestic, sedative, muscle relaxant, and anticonvulsant properties. It is very
widely used because of its more rapid onset of action and shorter duration of effect
compared with diazepam (Tolia et al., 2000). Disadvantages of midazolam include transient
hypotension and vomiting. Midazolam is approved for many routes, including intravenous,
oral and nasal and is most useful for intravenous sedation. Because of greater clearance of
midazolam in children, larger weight-adjusted dosages may be required in pediatric
patients than in adult to achieve similar levels and duration of sedation (Gilger, 1993 & Tolia
et al., 2000). The shorter clinical half-life of the drug necessitates additional boluses for
longer or complicated procedures. Less midazolam is needed when fentanyl is administered
than when meperidine is given with midazolam. Initial intravenous dose of midazolam is
0.025-0.1 mg/kg and may repeat another dose, but the maximum recommended dose is 0.4-
0.6 mg/kg. In our endoscopy center, we commonly use midazolam combined with low dose
propofol and/or low dose fentanyl.
Ketamine is a phencyclidine derivative with dissociative sedative, analgesic and amnestic
properties (Green & Krauss, 2000). It is one of the most sedative-analgesic agents and results
in a number of desired clinical effects that are dose dependent (Krystal et al., 1994). Typically
spontaneous respiration and airway reflexes are maintained although may not be totally
normal. Neuropsychiatric effects of ketamine include visual hallucinations that may be
accompanied by emergence phenomena and agitation. Ketamine generally causes an increase
in heart rate, blood pressure, cardiac output, intracranial pressure, and intraocular pressure.
Ketamine can induce salivation, and cholinergics have traditionally been coadministered.
The single most severe adverse effect with ketamine sedation is laryngospasm. Ketamine is
clinically effective by a number of different routes. Intravenous dose of ketamine is 1-1.5
mg/kg, and may repeat dose every 10 minutes as needed. In Thailand, we commonly used
low dose of ketamine, and combined with low dose of midazolam, opioid drug, and/or low
dose of propofol (Amornyotin et al., 2009). This combination technique produces stable
hemodynamic effects, and can reduce the sedation related adverse effects.
The ideal combination of sedative drugs for intravenous sedation in pediatric patients
undergoing gastrointestinal endoscopic procedure is unknown. The drug combination
provides synergistic action while lowering the doses of each agent. The combination
regimen may be a superior sedation technique (Cohen et al., 2004; Van Natta & Rex, 2006).
Our practice reflects this technique where many different combination regimens were used.
Midazolam and fentanyl are the most common agents used in combination with propofol in
this study. The next most common combination includes midazolam, fentanyl, ketamine,
Cardiopulmonary complications account for more than half of the major complications
during endoscopy (Lamireau et al., 1998) and are often related to hypoxia, especially in
children less than 1-year old (Lamireau et al., 1998 & Lightdale et al., 2008). In a study by
Barbi et al., using propofol in 811 children undergoing upper endoscopy, desaturation on
supplemental oxygen is 3%, and major desaturation was noted in 0.7% of all the children.
Additionally, a study by Yldzdas et al. demonstrated that the use propofol and midazolam⁄
fentanyl in 126 children who were randomly assigned to different sedation regimens had a
16.6% incidence of respiratory depression as shown by high end-tidal carbon dioxide (>50
mmHg). The higher incidence of respiratory depression reflected the better detection of
respiratory depression by the use of end-tidal carbon dioxide. The adverse events in our
clinical practice are comparable to those in the studies that did not use end-tidal carbon
dioxide monitoring (Balsells et al., 1997; Malviya et al., 1997 & Barbi et al., 2006).
4. Post-pediatric gastrointestinal endoscopic period (Recovery and
Following sedation it is important that patient monitoring continue until the children are
fully awake and ready for discharge. The recovery area should be equipped with oxygen,
suction, and equipment for tracheal intubation. Monitoring equipment including non-invasive
blood pressure, pulse oximetry, electrocardiography, and ventilation monitoring should be
available as well. Patients should be discharged only when they have met specific criteria.
The criteria for discharge should include:
stable vital signs
a return to the level of consciousness that is similar to the baseline for that patient
pain under control
adequate muscle strength to maintain a patent airway
speech and ambulation appropriate for age should return to pre-sedation level
nausea and/or vomiting should be controlled.
Patients who received reversal drugs such as naloxone or flumazenil may require longer
periods of observation, because the half-life of the offending agent may exceed that of the
reversal medication and lead to resedation. At the time of discharge, specific written and
verbal instruction and information as well as the status of the child should be given to a
parent, legal guardian or other responsible adult. Specific instructions should be given to the
child’s family instructing them what to do if the child should appear sedated or have any
other medical problems. In the western countries, most of GIE procedures for children can
be safely done with ambulatory setting. However, the majority of pediatric GIE procedures
in eastern countries like Thailand are done with inpatient setting.
In summary, no method of intravenous sedation can be universally applied to all children
requiring gastrointestinal endoscopic procedures. However, in a tertiary care teaching hospital
in a developing country, intravenous sedation for pediatric gastrointestinal endoscopic
procedures can be safely and effectively performed outside the operating room with a multi-
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