**10.2 Benzodiazepines**

#### **10.2.1 Midazolam**

50 Gastrointestinal Endoscopy

are avoidable. Children below one year are at the highest risk and need special attention. Desaturation and apnea are the most frequently encountered adverse effects which can be quickly reversed with administration of 02/ increasing flow. Uniform guidelines for both in hospital and out of hospital sedation must include appropriate personnel skilled in airway management and resuscitation. Health care personnel who sedate children for procedures

Table 3. Incidence of various adverse events observed over a period of two and a half years following endoscopies at the pediatric gastroenterology division of All India Institute of

The main classes of drugs used for sedation analgesia for diagnostic and therapeutic procedures are narcotics, benzodiazepines, systemic anesthetics and reversal agents. They

Fentanyl is a fat-soluble drug that rapidly enters the blood–brain barrier. It is more potent and fast acting than both morphine and meperidine. Fentanyl should be administered to children as a slow IV push since rapid administration has been associated with chest wall and glottic rigidity. Fentanyl's onset of action is approximately 30 seconds, and its opioid effects last approximately 30 to 45 minutes. Fentanyl should be administered in small doses to slowly titrate to effect, with several minutes allowed between each dose. Because its termination of action occurs with redistribution rather than from metabolism, the

Until recently, meperidine was a favorite in longer procedures since its clinical duration of action is 2–4 hours. It may be given intravenously in dosage of 0.5–1.0 mg/kg, with maximum being 4 mg/kg. The time of peak effect for meperidine is 1–3 minutes after intravenous administration. In addition to respiratory depression, the active metabolite meperidine (nor-meperidine) may cause seizures. Meperidine should not be used long-term or in patients with poor renal clearance. Special consideration includes avoidance in patients taking monoamine oxidase inhibitors and in patients with cardiovascular instability. The other adverse reactions following meperidine include delirium, nausea, vomiting, urinary retention, pruritis, smooth muscle spasm, and hypotension. Central nervous system toxicity may occur in patients taking tricyclic antidepressants and phenothiazines. Meperidine in the past was commonly used as a cocktail mixed with promethazine and chlorpromazine. The cocktail is still, on occasion, used by some but it has very long sedation duration, anywhere

must have advanced airway and resuscitation skills.

Medical Sciences, New Delhi, India

**10. Pharmacological options** 

**10.1 Narcotics 10.1.1 Fentanyl** 

are described briefly in the following paragraphs.

**10.1.2 Meperidine and the lytic cocktail** 

respiratory depressive effects of fentanyl outlast its analgesic effects.

**Adverse event N=4874**  Ineffective sedation 351 (7.2%) Respiratory depression (Hypoxemia) 975 (20%) Bronchospasm/ laryngospasm 101 (0.21%) Combativeness/delirium 238 (0.49%) Allergic reaction to drugs 118 (0.24%) Midazolam has now become the preferred drug in many pediatric endoscopy suites. It is a benzodiazepine with three to six times greater potency than diazepam. It is given in the dose of 0.1-0.3 mg/kg/dose intravenously. Midazolam provides three advantages over diazepam. It provides patients better anterograde and retrograde amnesia for the procedure. It has a shorter half life and there appears to be no resedation as seen with diazepam. The onset of action for a dose of midazolam is within 1 to 5 minutes, and it achieves its peak effect in approximately 30 minutes to 1 hour. Unlike other benzodiazepines, the clearance of midazolam is dose related (i.e., increased clearance with increased dosage).

#### **10.3 Systemic anesthetics**

#### **10.3.1 Ketamine**

Ketamine in low doses can cause intense analgesia with minimal respiratory and cardiovascular depression. Typical doses are 1–2 mg/kg intravenous. The onset occurs in less than 1 minute, with a peak effect in several minutes and duration of action in approximately 15 minutes. Higher doses (2mg/kg) or supplementation with other sedatives or narcotics may produce deep sedation or general anesthesia. Ketamine should always be administered with an atropine (0.1 mg/kg) or glycopyrrolate (0.01 mg/kg) since profuse secretions from ketamine alone may induce laryngospasm.

Cardiovascular stability and blood pressure are usually maintained. Typically, ketamine has been associated with hallucinations during emergence in up to 12% of patients. It may be reduced by administration of benzodiazepam. It is contraindicated in patients with head injury, open globe injury, hypertension, and psychosis. It is recognized that ketamine can induce apnea in neonates as well as a decrease response to hypocarbia, laryngospasm, and coughing. There is no antagonist available.

#### **10.3.2 Propofol**

Propofol is a short-acting sedative hypnotic. It is available in an Intralipid formulation. It has no analgesic properties, but it does have antiemetic and antipruritic properties. Although small doses of propofol (25–50 μg/(kg min) can provide "conscious sedation'' in adults with deep sedation, airway obstruction quickly occurs in pediatric patients. It is titrated with an infusion pump and should be administered by individuals with advanced airway skills. There has been a lot of enthusiasm in using this agent in pediatric intensive care units and in Endoscopy suites. Cases of fatal metabolic acidosis, mild cardiac failure, and lipemic serum have been reported in children which limits its use for prolonged periods of time. Short-term sedation with propofol has been associated with no such problems. Propofol should be administered in large veins since it can cause pain on injection. Respiratory depression/apnea and hypotension are related to the dose, rate and coadminstration with other CNS depressants. Hypotension occurs from using the medication, especially when it is given rapidly. Anaphylactic reactions and bacterial contaminations have been described and have been attributed to the lipid formulation in which it is dispensed. Strict aseptic technique must be used when one uses propofol because it may

**5** 

**Intravenous Sedation for** 

**Pediatric Gastrointestinal** 

*Siriraj Hospital, Mahidol University, Bangkok,* 

Somchai Amornyotin

*Thailand* 

**Endoscopy in a Developing Country** 

*Department of Anesthesiology and Siriraj GI Endoscopy Center, Faculty of Medicine,* 

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

*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.

*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

**1. Introduction** 

procedures.

commands.

maintained.

area of pediatric intravenous sedation.

The guideline defines terms throughout and in particular:

Cardiovascular function is usually maintained.

a patent airway. Cardiovascular function may be impaired.

support the growth of microorganisms. The dosage of this drug should be lowered if the patients are hemodynamically unstable. There is no antagonist available for this drug.

#### **10.4 Antagonists/reversal agents**

Flumazenil is a specific benzodiazepam antagonist and will rapidly reverse the sedative and respiratory effects of benzodiazepines. In patients who are taking benzodiazepines for seizures or drug dependency, seizures may recur if flumazenil is given. The recommended dose of flumazenil is 10 μg/kg up to 1 mg intravenously. Antagonism begins within 1–2 minutes and lasts approximately 1 hour. Since resedation after 1 hour is known to occur with diazepam, the patient must be carefully monitored for at least 2 hours. Flumazenil should not be administered for the routine reversal of the sedative effects of benzodiazepam, but reserved for reversal of respiratory depression only.

Naloxone reversal of meperidine due to respiratory depression may precipitate seizures caused by normeperidine. The initial dose for respiratory depression is 1–2 μg/kg titrated to affect every 2–3 minutes. A dose of 10–100 μg/kg up to 2 mg may be required for respiratory arrest.

#### **11. Conclusions**

Sedation for pediatric endoscopy is generally given to have a smooth and comfortable procedure. With proper safety precautions and adopting uniform guidelines, adverse events can be reduced to very low levels. However, pediatric endoscopy team must always be prepared for severe respiratory adverse events.

#### **12. References**

