**3. Current approaches to sedation for GI endoscopy**

### **3.1 Unsedated endoscopy**

32 Gastrointestinal Endoscopy

In conclusion, propofol is a more "powerful" drug than midazolam in producing sedation, which makes it very useful in gastrointestinal endoscopic sedation, but requires a higher

Fospropofol is a pro-drug used for sedation in a variety of endoscopic procedures including colonoscopy (Fechner *et al*, 2004; Gibiansky *et al*, 2005). It is converted to propofol in a few minutes after intravenous injection and inactive metabolites: phosphate and formaldehyde (rapidly converted to formate). Therefore, the time for maximum plasma concentration is higher than for propofol and the elimination period is slower.This effect facilitates the administration, because for short-term endoscopic procedures such as upper endoscopy or

To improve pain control and to facilitate moderate sedation control, fospropofol is coadministered with a narcotic, typically fentanyl. Fospropofol is associated with slight increases in phosphorus serum levels after intravenous administration, but no significant clinical adverse effects are present as a result of these elevated levels of phosphorus (Fechner *et al*, 2004; Gibiansky *et al*, 2005). These apparent disadvantages were considered by the U.S. Food and Drug Administration (FDA) as "benefits" of this drug, and therefore recently approved (2008) for moderate sedation in gastroscopy. Any other requests for drugs approval to be used for deep sedation in gastroscopy were refused. FDA requires that fospropofol be used only by persons trained in general anesthesia (only anesthesist) and that all patients should be monitored continuously by the medical staff not involved itself in the

Fospropofol does not cause pain at the injection site and is soluble in water. However, it has some side effects that are not described in propofol - particularly perineal pain or paresthesia (Fechner at al., 2004). Despite this, a preliminary report of a clinical trial

Droperidol is a neuroleptic butyrophenone used for conscious sedation in gastroscopy especially in the USA (Horn&Nesbit, 2004). It also has antiemetic action at low doses, explained by it occupying a GABA receptor. If it is used in the precursory period of endoscopic procedures, it can cause dysphoria, characterized by an apparent state of calm that masks in fact the anxiety generated by the endoscopic act. As a dopamine antagonist, droperidol may cause extrapyramidal side effects that can be countered by combination with promethazine or difenilhidramine. Droperidol determines cerebral vasoconstriction, but does not reduce cerebral metabolic rate, which may be detrimental to patients with cerebrovascular disease undergoing GI endoscopy. It does not produce amnesia and does not have anticonvulsant properties. Due to a weak alpha blocking action, may reduce blood pressure, significant effect in hypovolemic patients and Parkinson's disease. It protects the heart of the anti-arrhythmic effects of catecholamine release. One of the advantages of droperidol is that the response to the CO2 does not change, moreover, given intravenously, stimulates the respiratory response to hypoxemia, which is recommended for patients with COPD premedication. Neuroleptanalgesia produced by droperidol is characterized by a similar trance state in which the patient is immobile and unresponsive to external stimuli. Analgesia is strong, allowing the endoscopic procedure. Combined with fentanyl it does not

Promethazine is a powerful H1 antihistamine with antiemetic, anticholinergic, hypnotic, sedative/tranquilizing, analgesic and local anesthetic properties. It is used as an adjunct to

level of monitoring of vital functions.

endoscopic procedure.

colonoscopy, patients may require only one dose of fospropofol.

indicates that patient satisfaction is very good (Pruitet al, 2005).

provide stronger analgesia, but extends its duration (Ionescu, 2005).

endoscopic sedation and sedative in pediatrics.

Trials have shown that a substantial proportion of the patients from Asia, Europe and Canada are subjected to digestive endoscopic exploration without any sedation (Wang&Lin, 1999). This practice is not common in the United States of America and Australia. There is evidence that the low prevalence of endoscopy without sedation is due more to patient reserves, rather than physician preference (Faulx *et al*, 2005).

In terms of patient tolerance, a Finn double-blind trial compared intravenous midazolam alone with each of three other groups: one group without any sedation, a group that used a local pharynx anesthetic and a third control group (Ristikankare *et al*, 2004). Patients in the Midazolam group could not remember the procedure and reported desire to return to repeat the procedure. The effects were more pronounced in younger patients. Regarding the assessment of the endoscopist, patients in the Midazolam group were assessed as being easier to intubate by the endoscopist compared with placebo group, but there was no difference between Midazolam group and pharyngeal anesthesia group or control group. Interestingly, Midazolam group had a higher difficulty rating at endoscopy and retching during the procedure, compared with the pharyngeal anesthesia group.

Another trial showed that performing endoscopy without sedation was moderately less well tolerated by patients but did not require a long time for the procedure, the risks were not higher and the patients' reserves to undergo a subsequent procedure did not increase (Bonta *et al*, 2003). In this study, however, there was no control group, only blinded (both patients and endoscopists), sedation and placebo groups. More recently, it was found that male patients, patients with previous bowel resection, those with a high body mass index (BMI) and those without gynecological surgery didn't need sedation to complete colonoscopy (Tsai *et al*, 2008).

Hypnosis has also been used to facilitate endoscopy (Conlong *et al*, 1999). Compared with intravenous Midazolam, its use was associated with greater patient discomfort (assessment made by the patient), and the lack of amnesia for the procedure. A higher technical difficulty of the endoscopist was also reported. However, using hypnosis led to less patient agitation, according to assessments made by independent observers compared with patients receiving throat spray and no intravenous sedation and those receiving midazolam.

### **3.2 Topical anesthesia**

The use of throat sprays with various local anesthetics (lidocaine, tetracaine and benzocaine) as preparation for endoscopy is widespread, although few studies have evaluated their effectiveness.

A recent meta-analysis (Evans *et al*, 2006) of five randomized controlled trials on 500 patients showed that the use of local anesthetic sprays reduced throat discomfort and technical difficulties evaluated by the endoscopist. The main adverse effects are inhibition of gag reflex and the risk of pulmonary aspiration. There have also been reported systemic adverse effects such as arrhythmias and convulsions due to absorption of topical pharmacological agent, however extremely rare.

Sedation Related to Gastrointestinal Endoscopy 35

For this reason, the determination of any pharmacological schemes for moderate endoscopic sedation should include an observation period supervised by an anesthesiologist, followed by a supervised drug administration period in which the anesthesiologist selects and

**Reversal agents Initial IV dose Onset of action Duration of action** 

Another important principle for moderate sedation in endoscopy is that combinations of drugs from different classes have synergistic effects, without being additive. Thus, even a small amount of narcotic can substantially reduce the required amount of benzodiazepines (Arrowsmith *et al*, 1991, Bailey *et al*, 1990) or propofol (Clarke *et al*, 2001, Cohen *et al*, 2004, Kern *et al*, 2004, Roseveare *et al*, 1998, Rudner *et al*, 1998) necessary to perform the endoscopy. Similarly, benzodiazepines have a synergistic effect with narcotics (Arrowsmith *et al*, 1991, Bailey *et al*, 1990) and propofol (Clarke *et al*, 2001, Cohen *et al*, 2004; Paspatis *et al*, 2002; Seifert *et al*, 2000, Reimann *et al*2000). The understanding and knowledge of the clinical impact of synergistic effects determine the appropriate selection of drug doses needed to

A final general principle for endoscopic moderate sedation is that each sedative agent has unique properties in terms of time period between intravenous injection and onset of sedative action and maximum drug effect (Huang&Eisen, 2004, Horn&Nesbit, 2004). If additional drug boluses are administered before reaching previous boluses plasmatic peak, the sedative effects may rapidly accumulate and may cause unwanted deeper levels of sedation. Therefore, for each pharmacological agent used, the clinician must wait an appropriate time to reach its maximum effect before injecting additional boluses of medication during the initial titration and during the maintenance phase of sedation. For example, midazolam has a longer period for achieving the maximum effect (8-12min) than diazepam (2-5 min) (Buhren *et al*, 1995). Propofol has a very short time to onset of action (45- 60 seconds) and undergoes a rapid metabolism. These features have led to the necessity of quite frequent propofol administration (especially when it is used as single agent) to maintain sedation levels. For this reason, propofol administration requires more specialized attention and supervision compared to narcotics and benzodiazepines. There is the possibility that non-anesthesiologists to administer propofol for endoscopy, but the pharmacological properties of the drug are quite different from those of currently used narcotics and benzodiazepines and therefore higher risks. The use of narcotics and benzodiazepines to produce moderate sedation is already familiar to most of the

Key points and practical issues concerning the use of pharmacological agents for sedation

• Endoscopy with intravenous sedation is a routine practice in many countries and therefore is very important that the selection of sedative drugs to be made for a maximum patient and endoscopist comfort and with minimal side effects. One option is

and analgesia in GI endoscopy (Thomson *et al*, 2010):

(for opioids) 0.2–0.4·mg (also IM) 1–2·min 45·min

(for benzodiazepines) 0.1–0.2·mg 30–60·s 30–60·min

distribute that medicine (Rex, 2006).

Table 4. Commonly used reversal agents

achieve moderate sedation.

endoscopists.

Naloxone

Flumazenil

There is a small risk of methaemoglobinemia (Kane *et al*, 2007) especially for benzocaine, and some evidence that aspiration may occur after local anesthetic with throat spray (Ertekin *et al*, 2000).

### **3.3 Sedation and analgesia agent used for endoscopy**

A key principle of medical sedation in GI endoscopy, especially in ambulatory units where narcotic and benzodiazepines administration have a long tradition, is that drugs should be administered in incremental dosages in order to achieve the desired sedative effect. Although certain patient characteristics (such as patient age, comorbidities, body mass, race, previous responses to sedation and routine use of oral narcotics or benzodiazepines) may help pre-establish the drug dose required to achieve adequate sedation, the exact dose that will be needed for a particular patient is impossible to be accurately predicted. This is because the pharmacological response of the patient is variable and individual to specific sedative agents. Therefore, the anesthesiologist is trying to achieve moderate sedation by administering an initial bolus selected through a process of clinical estimation and then to titrate the increased doses to achieve the desired sedative effect. The general principle is to start with a low dose, followed by an assessment of patient responsiveness, sedation lever and ventilatory and cardiovascular function and status, and then gradually continue with increasing doses. The knowledge of the pharmacokinetic properties of pharmacological agents used is critical. However, it is possible that a variable number of individual responses might exist for any sedative or analgesic used (Gourlay, 1988; Levy, 1989; Wood, 1989).


Table 3. Pharmacological properties of sedative agents for endoscopy (Roseveare *et al*, 1998; Rudner *et al*, 2003)

There is a small risk of methaemoglobinemia (Kane *et al*, 2007) especially for benzocaine, and some evidence that aspiration may occur after local anesthetic with throat spray

A key principle of medical sedation in GI endoscopy, especially in ambulatory units where narcotic and benzodiazepines administration have a long tradition, is that drugs should be administered in incremental dosages in order to achieve the desired sedative effect. Although certain patient characteristics (such as patient age, comorbidities, body mass, race, previous responses to sedation and routine use of oral narcotics or benzodiazepines) may help pre-establish the drug dose required to achieve adequate sedation, the exact dose that will be needed for a particular patient is impossible to be accurately predicted. This is because the pharmacological response of the patient is variable and individual to specific sedative agents. Therefore, the anesthesiologist is trying to achieve moderate sedation by administering an initial bolus selected through a process of clinical estimation and then to titrate the increased doses to achieve the desired sedative effect. The general principle is to start with a low dose, followed by an assessment of patient responsiveness, sedation lever and ventilatory and cardiovascular function and status, and then gradually continue with increasing doses. The knowledge of the pharmacokinetic properties of pharmacological agents used is critical. However, it is possible that a variable number of individual responses might exist for any sedative or analgesic used (Gourlay, 1988; Levy, 1989; Wood, 1989).

> **Duration of action**

Table 3. Pharmacological properties of sedative agents for endoscopy (Roseveare *et al*, 1998;

**Elimination half-life** 

Triphasic: 2.2 min, 20 min,

8 h

**Excretion metabolism** 

Hepatic; excreted in urine

Hepatic; Excreted in urine

Hepatic; excreted in urine

Hepatic; excreted in urine

Hepatic; excreted in urine

Hepatic and intestinal; excreted in urine

**3.3 Sedation and analgesia agent used for endoscopy** 

**Pharmacokinetics** 

Meperidine 5 2–4 h 2–7 h

Midazolam 1.0–2.5 2–6 h 1.8–6.4 h

Droperidol 5-10 2-4 h 2.3 h

Fentanyl ≤1.5 1–2 h 2–7 h

Diphenhydramine 1-10 2-6 h 2.4-9.3 h

Propofol <1 3–10 min

Rudner *et al*, 2003)

**action (min)** 

**Sedation agent Onset of** 

(Ertekin *et al*, 2000).

For this reason, the determination of any pharmacological schemes for moderate endoscopic sedation should include an observation period supervised by an anesthesiologist, followed by a supervised drug administration period in which the anesthesiologist selects and distribute that medicine (Rex, 2006).


Table 4. Commonly used reversal agents

Another important principle for moderate sedation in endoscopy is that combinations of drugs from different classes have synergistic effects, without being additive. Thus, even a small amount of narcotic can substantially reduce the required amount of benzodiazepines (Arrowsmith *et al*, 1991, Bailey *et al*, 1990) or propofol (Clarke *et al*, 2001, Cohen *et al*, 2004, Kern *et al*, 2004, Roseveare *et al*, 1998, Rudner *et al*, 1998) necessary to perform the endoscopy. Similarly, benzodiazepines have a synergistic effect with narcotics (Arrowsmith *et al*, 1991, Bailey *et al*, 1990) and propofol (Clarke *et al*, 2001, Cohen *et al*, 2004; Paspatis *et al*, 2002; Seifert *et al*, 2000, Reimann *et al*2000). The understanding and knowledge of the clinical impact of synergistic effects determine the appropriate selection of drug doses needed to achieve moderate sedation.

A final general principle for endoscopic moderate sedation is that each sedative agent has unique properties in terms of time period between intravenous injection and onset of sedative action and maximum drug effect (Huang&Eisen, 2004, Horn&Nesbit, 2004). If additional drug boluses are administered before reaching previous boluses plasmatic peak, the sedative effects may rapidly accumulate and may cause unwanted deeper levels of sedation. Therefore, for each pharmacological agent used, the clinician must wait an appropriate time to reach its maximum effect before injecting additional boluses of medication during the initial titration and during the maintenance phase of sedation. For example, midazolam has a longer period for achieving the maximum effect (8-12min) than diazepam (2-5 min) (Buhren *et al*, 1995). Propofol has a very short time to onset of action (45- 60 seconds) and undergoes a rapid metabolism. These features have led to the necessity of quite frequent propofol administration (especially when it is used as single agent) to maintain sedation levels. For this reason, propofol administration requires more specialized attention and supervision compared to narcotics and benzodiazepines. There is the possibility that non-anesthesiologists to administer propofol for endoscopy, but the pharmacological properties of the drug are quite different from those of currently used narcotics and benzodiazepines and therefore higher risks. The use of narcotics and benzodiazepines to produce moderate sedation is already familiar to most of the endoscopists.

Key points and practical issues concerning the use of pharmacological agents for sedation and analgesia in GI endoscopy (Thomson *et al*, 2010):

• Endoscopy with intravenous sedation is a routine practice in many countries and therefore is very important that the selection of sedative drugs to be made for a maximum patient and endoscopist comfort and with minimal side effects. One option is

Sedation Related to Gastrointestinal Endoscopy 37

respect. Conscious sedation can be used successfully in cooperating children, using combinations of opioids with benzodiazepines or nitrous oxide alone (Michaud, 2005;

Minimum anesthesia for upper endoscopy in children does not require tracheal intubation as diagnostic procedures may take no longer than 10 minutes and cause no significant unpleasant effects afterwards. Two key points for the safety of the procedure should be highlighted: the endoscope can compress and obstruct the trachea (especially in infants) (Barbi *et al*, 2006; Casfeel *et al*, 1992) and achalasia is very dangerous (esophageal residue should be drained before any sedation or anesthesia in children). Tracheal intubation is much safer in these two situations. The anesthesia for endoscopy lasting 15-30 min, can be more easily done with a device for airway intubation, such as masks (Rauch&Brener, 2003)

Minimum anesthesia with an initial bolus of propofol (2-3 mg/kg) will suppress the gag reflex enough to allow easy introduction of the endoscope, and smaller doses as boluses or continuous infusion are also effective later on (Barbi *et al*, 2006; Khoshoo *et al*, 2003; Kaddu *et al*, 2002, Walker *et al*, 2003, Perera *et al*, 2006). Usually, no additional opioids are

In children sedated endoscopy, two aspects are important: the safety of a technique in which gastric contents are not aspirated and the endoscopist's training and skill in using propofol. Barbi *et al* reported their experience in propofol use in a study involving 811 children who received upper endoscopies (Barbi *et al*, 2006). Desaturation (SpO2 <90%) occurred in 16% of cases, but this was reduced to only 3% when supplemental oxygen was administered. Major desaturation occurred in six cases, three of them being infants (12% of all children). They required assisted ventilation by face mask and endoscopy was abandoned in three cases. None of them aspirated the gastric content in their lungs and did not require tracheal intubation. The anesthesia was made by non- anesthetists in all cases. In a study with a smaller group of 57 children, Perera *et al* (pediatric anesthesiologists) have successfully used Propofol, only a child was given suxamethonium to remove the occurring laryngospasm

Some small retrospective trials regarding intravenous sedation during upper and lower gastrointestinal endoscopy in pregnant women showed that there were no maternal or fetal adverse effects, nor did it associate congenital malformations (Capella *et al*, 1996a, 1996b). Notwithstanding this goal, endoscopy should be avoided during pregnancy, and if possible, especially during the first trimester of pregnancy to avoid potential teratogenic effects during embryogenesis. However there should be some therapeutic safety guidelines or protocols which include a minimum set of safety procedures in case of use of anesthetic care especially in emergency situations. In pregnant patients with higher gestational age, a lying position should be avoided because the uterus could compress the aorta and inferior vena

Frequently administered benzodiazepines (midazolam and diazepam), fentanyl and propofol are all classified by the Australian Drug Evaluation Committee (Australian Drug Evaluation Committees [ADECE], 1999) as part of category "C", as their pharmaceutical effects may cause potential harmful effects on the human fetus or neonate without causing

or laryngeal mask with a special port for the endoscope (Lopez-Gil *et al*, 2006).

(Perera *et al*, 2006). Tracheal intubation was not necessary.

**3.5 Anesthesia and sedation in pregnant and lactating women** 

Annequin *et al*, 2000).

needed.

cava.

malformations.

to spray the throat with local anesthetic that could be associated with soothing music, reducing the necessary amounts of intravenous sedative drugs.


#### **3.4 Anesthesia and sedation in pediatric gastrointestinal procedures**

In children there are some particular morphological characteristics: the tongue fills the upper airways more than in adults, while the tonsils and adenoids may compromise the airway freedom. In addition, relatively high oxygen consumption in children and larger surface may lead to clinically significant hypoxemia, dehydration and hypothermia if not provided adequate strategies to prevent them. Endoscopy performed especially in children under 10 years of age almost always requires deep sedation with endotracheal intubation. In order to reduce the anxiety caused by the separation from parents and to improve the implementing of an intravenous catheter the physician can orally administer low doses of midazolam (0.5 mg/kg) (Liacouras *et al* 1998) before the procedure, together with special counseling for children (Mahajan *et al* 1998).

In performing GI endoscopy in children, two types of sedation are being used: minimal sedation and deep anesthesia. In deep sedation, combinations of midazolam, fentanyl and ketamine are useful; however they must be used with caution (Balsells *et al*, 1997; Bahal-O'Mara *et al*, 1994; Bouchut *et al*, 1997, Green *et al*, 2001). Even with the extensive experience of the anesthetist, there is a risk of laryngo-spasm (Green *et al*, 2001) and hypoxia (Cote *et al*, 2000). Usually the recovery is prolonged and Naloxone and Flumazenil antagonists are often required (Balsells *et al*, 1997; Lamireau *et al*, 1998). General anesthesia performed by an anesthesiologist offers safe conditions to perform endoscopic procedures in children, however, is perceived by the endoscopists as being expensive and requiring specialized personnel. However, short-term action of certain drugs such as propofol (Khoshoo *et al*, 2003) and sevoflurane (Montes & Bohn, 2000) can reduce costs because the post-anesthesia recovery time is shorter. Colonoscopy performed in pediatric patients causes pain due to bowel distension, which may alert the endoscopist about a possible perforation of the colon. General anesthesia reduces colonic tone and, therefore, deep sedation may be safer in this

• The pre-procedural assessment of patients undergoing sedation endoscopy is very important. Cardiovascular, respiratory and neurological comorbidities should be rigorously evaluated. Allergies and adverse reactions to sedative drugs, smoking, alcohol consumption, routinely sedatives use should also be known. The person who used pharmacological agents and monitors the effects of sedative should evaluate the nature of the proposed procedure, its likely duration and the potential for

• Intravenous sedation for GI endoscopy should be administered only if there is sufficient space to allow easy personnel movement and require specialized monitoring equipment readily available: oximeter, frequent measurement of blood pressure, the

• Propofol and its pro-drug, fospropofol can be safely administered in quality moderate sedation without patient safety compromising with low doses of narcotics and/or

• Due to their pharmacological profiles, Midazolam, Fentanyl, Propofol and newer Fospropofol remain the most commonly used drugs for intravenous sedation in GI endoscopy. If sedatives are administered by the endoscopist, total dose of Midazolam

In children there are some particular morphological characteristics: the tongue fills the upper airways more than in adults, while the tonsils and adenoids may compromise the airway freedom. In addition, relatively high oxygen consumption in children and larger surface may lead to clinically significant hypoxemia, dehydration and hypothermia if not provided adequate strategies to prevent them. Endoscopy performed especially in children under 10 years of age almost always requires deep sedation with endotracheal intubation. In order to reduce the anxiety caused by the separation from parents and to improve the implementing of an intravenous catheter the physician can orally administer low doses of midazolam (0.5 mg/kg) (Liacouras *et al* 1998) before the procedure, together with special

In performing GI endoscopy in children, two types of sedation are being used: minimal sedation and deep anesthesia. In deep sedation, combinations of midazolam, fentanyl and ketamine are useful; however they must be used with caution (Balsells *et al*, 1997; Bahal-O'Mara *et al*, 1994; Bouchut *et al*, 1997, Green *et al*, 2001). Even with the extensive experience of the anesthetist, there is a risk of laryngo-spasm (Green *et al*, 2001) and hypoxia (Cote *et al*, 2000). Usually the recovery is prolonged and Naloxone and Flumazenil antagonists are often required (Balsells *et al*, 1997; Lamireau *et al*, 1998). General anesthesia performed by an anesthesiologist offers safe conditions to perform endoscopic procedures in children, however, is perceived by the endoscopists as being expensive and requiring specialized personnel. However, short-term action of certain drugs such as propofol (Khoshoo *et al*, 2003) and sevoflurane (Montes & Bohn, 2000) can reduce costs because the post-anesthesia recovery time is shorter. Colonoscopy performed in pediatric patients causes pain due to bowel distension, which may alert the endoscopist about a possible perforation of the colon. General anesthesia reduces colonic tone and, therefore, deep sedation may be safer in this

complications. This person should ideally be a physician anesthesiologist.

and Fentanyl should not exceed 5 mg and 100 micrograms, respectively.

**3.4 Anesthesia and sedation in pediatric gastrointestinal procedures** 

counseling for children (Mahajan *et al* 1998).

reducing the necessary amounts of intravenous sedative drugs.

insertion of intravenous cannula for the fluids administration.

benzodiazepines and ideally by a physician anesthesiologist.

to spray the throat with local anesthetic that could be associated with soothing music,

respect. Conscious sedation can be used successfully in cooperating children, using combinations of opioids with benzodiazepines or nitrous oxide alone (Michaud, 2005; Annequin *et al*, 2000).

Minimum anesthesia for upper endoscopy in children does not require tracheal intubation as diagnostic procedures may take no longer than 10 minutes and cause no significant unpleasant effects afterwards. Two key points for the safety of the procedure should be highlighted: the endoscope can compress and obstruct the trachea (especially in infants) (Barbi *et al*, 2006; Casfeel *et al*, 1992) and achalasia is very dangerous (esophageal residue should be drained before any sedation or anesthesia in children). Tracheal intubation is much safer in these two situations. The anesthesia for endoscopy lasting 15-30 min, can be more easily done with a device for airway intubation, such as masks (Rauch&Brener, 2003) or laryngeal mask with a special port for the endoscope (Lopez-Gil *et al*, 2006).

Minimum anesthesia with an initial bolus of propofol (2-3 mg/kg) will suppress the gag reflex enough to allow easy introduction of the endoscope, and smaller doses as boluses or continuous infusion are also effective later on (Barbi *et al*, 2006; Khoshoo *et al*, 2003; Kaddu *et al*, 2002, Walker *et al*, 2003, Perera *et al*, 2006). Usually, no additional opioids are needed.

In children sedated endoscopy, two aspects are important: the safety of a technique in which gastric contents are not aspirated and the endoscopist's training and skill in using propofol. Barbi *et al* reported their experience in propofol use in a study involving 811 children who received upper endoscopies (Barbi *et al*, 2006). Desaturation (SpO2 <90%) occurred in 16% of cases, but this was reduced to only 3% when supplemental oxygen was administered. Major desaturation occurred in six cases, three of them being infants (12% of all children). They required assisted ventilation by face mask and endoscopy was abandoned in three cases. None of them aspirated the gastric content in their lungs and did not require tracheal intubation. The anesthesia was made by non- anesthetists in all cases. In a study with a smaller group of 57 children, Perera *et al* (pediatric anesthesiologists) have successfully used Propofol, only a child was given suxamethonium to remove the occurring laryngospasm (Perera *et al*, 2006). Tracheal intubation was not necessary.

#### **3.5 Anesthesia and sedation in pregnant and lactating women**

Some small retrospective trials regarding intravenous sedation during upper and lower gastrointestinal endoscopy in pregnant women showed that there were no maternal or fetal adverse effects, nor did it associate congenital malformations (Capella *et al*, 1996a, 1996b). Notwithstanding this goal, endoscopy should be avoided during pregnancy, and if possible, especially during the first trimester of pregnancy to avoid potential teratogenic effects during embryogenesis. However there should be some therapeutic safety guidelines or protocols which include a minimum set of safety procedures in case of use of anesthetic care especially in emergency situations. In pregnant patients with higher gestational age, a lying position should be avoided because the uterus could compress the aorta and inferior vena cava.

Frequently administered benzodiazepines (midazolam and diazepam), fentanyl and propofol are all classified by the Australian Drug Evaluation Committee (Australian Drug Evaluation Committees [ADECE], 1999) as part of category "C", as their pharmaceutical effects may cause potential harmful effects on the human fetus or neonate without causing malformations.

Sedation Related to Gastrointestinal Endoscopy 39

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safety and clinical efficacy of esophagogastroduodenoscopy in 83 pregnant females with follow-up of fetal outcome with comparison control groups. The American

and children during upper gastrointestinal endoscopy. Gastrointestinal Endoscopy,

In regard to women who are breastfeeding and want sedation for endoscopic procedures, data are limited. It is recommended that patients who received Midazolam should not breastfeed for at least 4 hours after its administration. Breastfeeding restriction time after propofol administration is not well documented, although it is likely to be higher because the maximum concentration in breast milk occurs in 4 to 5 hours after administration. Hence, it is indicated to collect breast milk in a container and subsequently throw it a few hours before resuming breastfeeding. Fentanyl administration is not considered a contraindication for breastfeeding (Qureshi *et al*, 2005).
