Reaction to being addressed
Patient reacts appropriately to verbal commands
Somnolence, reaction to louder commands with additional tactile stimulation if necessary
Somnolence, hard to wake, purposeful response after repeated or painful stimulation
Patient cannot be woken, not even in response to pain stimuli
The ability to independently maintain ventilatory function may be impaired. Patients may require assistance in maintaining a patent airway. Spontaneous ventilation may be inadequate.
Inadequate, ITN or larynx mask necessary
Diseases of the cardiovascular and respiratory system,
Stridor, snoring, sleep apnea syndrome
Complications on previous occasions when sedatives/analgesics, regional and/or general anesthesia were administered
Drug allergies, current medication, and possible drug interactions
Most recent meal: when and what was eaten
Tobacco, alcohol, drug consumption
Also a physical examination should be performed including vital signs and auscultation of heart and lung to indent potential cardio-respiratory problems that might occur during the procedure. A generally related classification is represented by the so-called ASA classification  (Table 28.2). Patients in ASA-class III or higher are known to have an increase risk due to sedation for gastrointestinal procedures. In addition, anatomical features are taken into account. A restricted mouth opening (classified according to the Mallampati score) might complicate the management of respiratory complications [1–3]. Such high risk patients are not suitable for sedation by trained nurses. In this situation one should consider to consult an anesthesiologist [1–3]. It is obligatory to provide appropriate emergency medicines and equipment such as defibrillator, equipment for airway management (bag-mask ventilation, endotracheal intubation) etc. [1–3]. Of course, should the endoscopy team also be familiar with the technique of cardiopulmonary resuscitation, refreshing it regularly as part of structured simulator courses [1–3].
Mild disease, not limiting daily activities
Severe disease, limiting daily activities
Severe disease, life-threatening
Latest guidelines [1, 2] recommend a routine oxygen administration via a nasal cannula (for example with 2–3 l/min). This is based on the knowledge of the increased occurrence of hypoxemia, particularly at interventional or longer lasting procedures or in patients with high co-morbidity, pulmonary impairment or with circulatory depression (e.g., emergency cases). The administration of oxygen starting at least 2 min before the examination can significantly reduce the frequency of severe hypoxia during the endoscopic procedure . If there is a pronounced hypercapnia, such as COPD, the oxygen supply must also be individually adjusted in order not to reduce the respiratory drive (by excessive O2 supplementation) . The guideline of the American gastroenterologists  does not recommend routine prophylactic administration of oxygen. Reason is the feared delay the detection of hypoxia. However, the majority of anesthesiologists believe that the benefits of pre-oxygenation outweigh this disadvantage [1, 2].
Since the transitions between the various stages of sedation (Table 28.3) are fluid, an appropriate patient monitoring is required for all patients by an independent appropriately trained person not involved in the endoscopic procedure [1–3]. The person in charge of monitoring clinically checks breathing by observation, palpation of thorax and abdominal wall movement, and possibly palpation of expiratory airstream.
Guideline recommendations for sedation with propofol
Limitations for NAPS
Indication for MAC
ASA > III
Yes (monitored by the doctor)
ASA ≥ III, Emergency and complex procedures, in cases of airway difficulties
ASA > III, high-risk patients, complex procedures
ASA > II, complex procedures, in cases of airway difficulties
ASA ≥ III and complex procedures or cases of airway difficulties
ASA ≥ III, complex procedures, in cases of airway difficulties
ASA ≥ III and deep sedation. Expected difficult airway management
Standard – Monitoring recommended by different international societies includes continuous pulse oximetry and automated noninvasive blood pressure measurement (at baseline and then at 3–5-min intervals) during both NAAP and the recovery period; continuous electrocardiography is recommended in selected patients with a history of cardiac and/or pulmonary disease. Baseline, minimum and maximum heart rate/blood pressure, as well as baseline and minimum oxygen blood saturation should be recorded [1–3].
Principal Options for Sedation
Diazepam is nowadays used very rarely because of its long half-life of 25–30 h, according to a first survey in Germany its application was stated only by around 8 % of respondents . In contrast, about 80 % of respondents use midazolam . Its pharmacological advantages are a shorter half-life (1,5–3 h), a better retrograde amnesia and a higher water solubility. Compared to diazepam patient tolerance and sedation efficiency are consistently well . A combination of benzodiazepines and opioids (predominantly midazolam plus meperidine) was used in about one third of all gastroenterologist for colonoscopy . The use in diagnostic endoscopy of the upper digestive tract (e.g., diagnostic EUS), however, is considered obsolete . The advantage of a combination of benzodiazepines and opioids at endoscopy is highly controversial and can be seen rather negatively according to recent data [1, 2].
Propofol: The New Standard
With respect to the introduction of the short-acting propofol (plasma half-life of 7–8 min) legal and personnel requirements are still the center of discussion. Numerous guidelines for sedation in endoscopy [1–3, 9–16], were counted in the last years worldwide, their recommendations for the use of propofol are summarized in Table 28.3. All guidelines are uniform on the assumption that the endoscopist themselves can not perform the endoscopic procedure, patient monitoring and propofol administration at the same time. Demanded is therefore a further, independent assistant person not involved in the endoscopic procedure. This can be a qualified caregiver (so called NAPS, “nurse administered propofol sedation”) a second specialist in internal medicine or a gastroenterologist (usually called “ gastroenterologist -directed propofol sedation, G-DPS ”) or an anesthesia team (“monitored anesthesia care, MAC”). While in principle all guidelines advocate “MAC”, they differed with respect to the recommendation when the gastroenterologist should consider the use of anesthesia mandatory (Table 28.3). Provided however, is that the patient is monitored according to the rules of science and that for any incident the necessary personal and instrumental equipment is given [1–3]. The qualification of medical and non-medical personnel should be maintained by regular participation in structured training curricula as developed on national  or European basis  ensuring to comply with this legal requirement in different countries and again to meet the personal requirements postulated. This is of course not only in addition to the use of propofol, but also for the use of other substances for sedation or analgesia. While currently only isolated special training guidelines exist on premedication and management of emergency situations, it could have shown that specific training courses, such as those based on simulators, might improve physicians’ confidence in handling emergency situations .
Propofol has the distinct advantage of sedation compared to benzodiazepines, that the effect occurs much faster  and patients recover more rapidly [21–30]. This also applies to the regeneration of psychomotor functions, when propofol was compared with gastroscopy or colonoscopy with a combination of midazolam and meperidine by using a driving simulator . Similar results were published by a study from Japan comparing propofol with midazolam for EGG . The possible improvement of diagnostic accuracy in the EGD appears an additional advantage of propofol compared to midazolam in a randomized controlled trial by Meining et al. .
Regarding sedation with propofol the investigators evaluated the patients acceptability and tolerance for both the gastroscopy and colonoscopy, as well as for the ERCP in comparison to benzodiazepines as better [24, 25] or equally well [21, 33, 34]. In particular, for interventional examinations such as ERCP also a significantly better patient cooperation could have been shown [26, 27, 35]. Especially with the use of propofol for interventional studies one has to consider that this is not entirely without risk, as shown by data on a risk factor analysis . Of 9547 patients who received propofol sedation, during the interventional upper endoscopy (EGD, ERCP, EUS) over a period of 6 years, 3151 patients received propofol as mono-sedation and the remaining 6396 a combination of propofol and midazolam. There were a total of 135 serious complications, premature termination of the procedure had to be made in 1.4 %. In 40 patients (0.4 %) a short-term mask ventilation and in nine patients (0.09 %) endotracheal intubation was necessary, another eight patients (0.08 %) had to be monitored on the ICU. Four patients died (mortality rate 0.03 %), in three cases potentially sedation associated side effects must be considered. As independent risk factors for the occurrence of cardiorespiratory complications emergency examinations and a higher dose of propofol were identified .
Risk Patients: Propofol or Midazolam?
Both during the investigation and in the post-intervention phase under midazolam elderly patients are at increased risk of documented hypoxemia [37, 38]. In the elderly, it is therefore appropriate to reduce the dose of midazolam . This also suggests the modification of the recommendations of the American Society of Gastroenterology for older patients undergoing gastrointestinal endoscopy . In addition, substances with low cumulative dose [40, 41] should be preferred. The careful use of propofol due to its pharmacokinetic is even safe for high-risk patients aged over 85 years, as we could have shown in a randomized trial comparing propofol with a combination of midazolam and meperidine for ERCP . Similar findings were obtained in a study by Heuss et al. . Since cardio-respiratory events tend to occurred more frequently, there need to be increased care in these patients. Patients with liver cirrhosis are another risk group, where a hepatic encephalopathy may increase under midazolam [43–46]. This can lead to an unforeseen anesthetic stage during sedation, a prolonged wake up period with reduced psychomotor skills. In randomized controlled trial comparing midazolam with propofol for sedation in patients with liver cirrhosis undergoing interventional EGD the mentioned side effects did not occur when using the ultra-short acting propofol .
Propofol and Midazolam (So-Called Balanced Sedation)
The propofol dose required can significantly be reduced “co-induction” with small amounts of midazolam (usually 2–3 mg) [30, 47], what particularly in often prolonged interventional endoscopic procedures is possible and valid only for this. For short duration procedures, most of which are diagnostic, should be dispensed with a co-induction with midazolam, because the savings effect is only insignificantly. In addition, the advantage of rapid psychomotor recovery when using propofol as a single agent  and the associated possibility of faster release should not be forgiven (discharge from the recovery room to the ward or outpatient examinations) in these cases.
Propofol Plus Midazolam or Opiates
Cordruwisch et al.  performed sedation in 64 patients, who underwent two successive, prolonged (>30 min) endoscopic examinations following up each other. In the first procedure sedation was performed with propofol and in the subsequent examination with a combination of midazolam and propofol. The combination had the advantage of a considerable saving effect of 59 % propofol. However post-interventional wake up was twice as long as in the propofol mono-sedation group (8 min versus 4 min). Van Natta et al.  examined in another randomized study 200 patients who received sedation with propofol either alone, propofol plus fentanyl, propofol plus midazolam or midazolam plus fentanyl. By combining process thereby moderate sedation with a shorter recovery time was reached. On the other hand correspondingly higher doses were required with sole administration of propofol, which induced a higher sedation depth leading to a substantially longer recovery time.
Propofol and/or Opiates
Akcaboy et al.  studied in a randomized trial in 100 patients during a colonoscopy, the sole administration of the short-acting analgesic drug remifentanil compared to mono-sedation with propofol. It was shown that remifentanil achieved an adequate sedation, amnesia and compared to propofol better analgesia. An increased incidence of nausea and vomiting during the recovery reduced this advantage, however, significantly. Moermann et al.  investigated the additive dose of remifentanil for sedation with propofol in a randomized double-blind trail in 50 relatively healthy patients (ASA I and II) undergoing colonoscopy. The combination of remifentanil and propofol showed significantly more often a decrease in blood pressure and oxygen saturation. By administering remifentanil the dose of propofol required could have been reduced, however, the recovery time under propofol mono-sedation was significantly shorter (p <0.01) and patients significantly more satisfied (p <0.01).