Ludzkie koronawirusy - autor: Krzysztof Pyrć z Zakładu Mikrobiologii, Wydział Biochemii, Biofizyki i Biotechnologii, Uniwersytet Jagielloński, Kraków

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© Borgis - Nowa Medycyna 1/2017, s. 27-36
*Jacek Wadełek
Pharmacology of analgosedation in adult patient during colonoscopy
Farmakologia analgosedacji u dorosłego pacjenta do kolonoskopii
Anaesthesiology and Intensive Therapy Department, St. Anna Trauma Surgery Hospital, STOCER Mazovia Rehabilitation Center Sp. z o.o., Warsaw
Head of Department: Elżbieta Kurmin-Gryz MD
Streszczenie
Kolonoskopia jest często uważana przez pacjentów za inwazyjną procedurę, która wkracza w intymność pacjenta i powoduje dyskomfort, dolegliwości bólowe i obawę związaną z wynikiem badania. Zastosowanie analgosedacji do kolonoskopii nie tylko poprawia tolerancję i satysfakcję pacjenta, ale również wolę pacjentów poddania się powtarzanym badaniom. Jedne ośrodki endoskopowe preferują głęboką analgosedację do kolonoskopii, która powoduje całkowite zniesienie dyskomfortu kolonoskopii, ale i utratę kontaktu słownego. Inne ośrodki endoskopowe preferują lekką analgosedację, kiedy pacjent ma zachowane zdolności kontaktu logiczno-słownego i spełnia polecenia, zmieniając ułożenie ciała podczas badania. Szeroko stosowanym sposobem analgosedacji do kolonoskopii jest połączenie propofolu z opioidem. Takie połączenie leków zwiększa komfort pacjentów, ale synergistyczne działanie depresyjne na układ oddechowy i układ krążenia obu leków może powodować zagrażające życiu działania niepożądane. Głębszy stopień analgosedacji pozwala lekarzowi na dokładniejsze i kompletne badanie kolonoskopowe. Kwalifikacja pacjenta do kolonoskopii z zastosowaniem analgosedacji nie różni się od kwalifikacji rutynowo przeprowadzanej przed znieczuleniem ogólnym. Podstawowe znaczenie mają dokładnie zebrany wywiad chorobowy i badanie fizykalne. Przed rozpoczęciem analgosedacji niezbędne jest uzyskanie świadomej zgody pacjenta lub jego opiekuna, wyrażonej na piśmie.
Summary
Colonoscopy is often viewed by patients as an invasive procedure which enters the patient’s intimate zone, causes discomfort and concerns about potential findings. These concerns can lead to anxiety, which affects patient cooperation and satisfaction with the procedure. The use of analgosedation for colonoscopy not only enhances patient tolerance and satisfaction, but also increases the willingness of patients to return for repeated examination. Deep sedation for colonoscopy, in which the colonoscopy-related discomfort is eliminated, but the verbal contact is lost, may be routinely practised in some countries and centres as opposed to conscious sedation, when the verbal contact is maintained and the patient responds to instructions, e.g. by changing body position during the examination. A combination of propofol with an opioid is widely used in analgosedation during colonoscopy. Although this combination increases patient comfort, the synergistic respiratory and circulatory depressant effects of both these agents may induce life-threatening adverse effects. This level of sedation may allow the colonoscopist to dedicate more time and attention to examining the colon during colonoscopy. It has been found that with the use of deep rather than conscious sedation, more advanced lesions may be found and more patients are likely to undergo complete colonoscopies. Qualification for colonoscopy with analgosedation does not differ from routinely used qualification before general anaesthesia. Most important are: detailed anamnesis and physical examination. Before starting anagosedation it is imperative to obtain informed consent from a patient or his/her legal guardian, expressed in writing.
Introduction
A screening colonoscopy is a validated tool for early diagnosis of colorectal cancer. This is an important reason why colonoscopy belongs to the most common endoscopic gastrointestinal examinations. However, motivating patients to participate in colonoscopy screening continues to be a challenge. The lack of knowledge about the procedure may be a significant barrier preventing patients from undergoing screening. Patients complain about disruption of normal daily activities by bowel preparation for colonoscopy, prolonged analgosedation after colonoscopy, as well as the need to be accompanied when returning home. There is an ongoing discussion on sedation-free colonoscopy, and there is no consensus in this regard. While in some countries it is a common practice to perform colonoscopy without sedation, this type of management is considered unfeasible and is not recommended in other countries. In countries where colonoscopy is performed under analgesia, a trend towards deeper levels of sedation may be observed (1). Sedation in colonoscopy increases the costs of examination. Also, the costs associated with absenteeism, additional personnel, the use of equipment for analgosedation and general anaesthesia as well as monitoring and surveillance of patients after colonoscopy under analgosedation should be considered. Additionally, patients complain about the need to be accompanied when returning home, about limited physical activity as well as the risk of anaesthesia-related complications. Analgosedation in colonoscopy should be considered for at least two reasons: 1) the patient may be anxious and afraid of violation of their physical intimacy, 2) due to colonoscopy-related pain. Each of these reasons requires the use of two different agents, with benzodiazepines being an appropriate choice for patients with fear and anxiety associated with intimacy, and opioids recommended for pain. Deep sedation using propofol or even general anaesthesia is another method used in some countries. Colonoscopy may be well-tolerated by some patients, with high levels of satisfaction and only minor or no pain, whereas in other cases the procedure may require deep sedation. The underlying causes are multifactorial and include such elements as previous abdominal surgeries and the resulting adhesions, individual anatomy of each patient, the skillfulness of an endoscopist, patient expectations, local traditions, endoscopic insertion technique and the type of endoscopic equipment.
Pain and discomfort during colonoscopy
Pain during colonoscopy is considered to be visceral, resulting from the activation of sensory afferent nerves that innervate the intestines. The main triggering factors include stretching of the sigmoid wall and mesenteric attachments due to excessive intestinal distension and colonoscope looping (2). Visceral pain often triggers autonomous reflexes, such as perspiration, bradycardia, vertigo, hypotension and nausea. Although pain is a physiological response to tissue damage, it also includes emotional and behavioural responses depending on the individual experiences and cultural background, which are often resistant to analgesic treatment. Young women with low body mass index (BMI) show lower pain tolerance as opposed to older patients. It is difficult to predict pain intensity in each patient.
Pain management and sedation for colonoscopy
Analgosedation for colonoscopy is currently a widely discussed issue. Sedation in colonoscopy is a standard management in the USA, with different studies recommending either moderate or deep sedation. Other parts of the world argue for medication-free colonoscopy (3). Eckardt et al. showed in their study including 2,500 patients that analgosedation-free colonoscopy was possible in 95% of patients if performed by an experienced endoscopist using optimal equipment. However, no reports on patient satisfaction with the performed endoscopic procedure were presented (4). Nowadays, the use of colonoscopes employing the water method, and experienced endoscopists make colonoscopy without sedation possible for a motivated group of patients (5-7). Success rates depend on appropriate patient selection. Male gender, higher levels of education, low preprocedural anxiety, and patient’s preference for procedures without sedation are predictors of a successful sedation-free procedure. However, unpredictable individual anatomical differences can lead to unacceptable discomfort for the patient and poor procedural conditions for analgosedation-free colonoscopy.
Methods of analgosedation
Levels of sedation, ranging from moderate to deep, are defined in sedation guidelines. Deep sedation is usually achieved using intravenous propofol, which has a rapid onset and short duration of action, allowing for a reduced recovery time. Therefore, there is an increasing interest in propofol-based sedation among gastroenterologists. It should be noted, however, that propofol has a relatively narrow therapeutic range, which increases the risk of sedation-related adverse effects. Most states in the United States do not allow the use of propofol by non-anaesthesiologists. In Poland, this anaesthetic is also used only by anaesthesiologists (8-12). The European guidelines allow for the administration of propofol by trained nurses or endoscopists who do not perform colonoscopy at the same time (13). However, this permission only concerns moderate, and not deep sedation. Deep sedation requires specialist equipment and training, and it may be performed only by trained personnel and under appropriate monitoring (14). The rates of colonoscopies performed by specialised anaesthetic teams increased from 23.9% in 2007 to 53.4% in 2015, respectively, and are still rising (15). Deep sedation may cause spontaneous ventilation failure, which may require assistance to maintain patent airways. An analysis of aesthetic-related adverse events registry demonstrated that serious adverse events can occur during deep sedation, even when performed by properly trained personnel (16). The most common adverse effects include respiratory depression, cardiovascular events, delayed recovery of consciousness, and prolonged time between analgosedation and hospital discharge. Deeply sedated patients are not able to change their body position during examination, which makes it difficult to maneuver the patient. Moderate sedation is defined as a drug-induced depression of consciousness. Moderately sedated patients are able to purposefully respond to verbal commands. Spontaneous ventilation is adequate, and there is no the risk of airway obstruction. Agents that are most commonly used for moderate sedation include midazolam and other benzodiazepines or midazolam combined with an opioid. Although combination of a sedative and an opioid is excellent for colonoscopy, it increases the risk of unintentional deep sedation and more common respiratory depression. The duration of analgosedatives may be longer than the duration of the procedure, resulting in prolonged recovery with a delay in hospital discharge, increased costs, and disruption of daily activities of the patients.
The ideal analgosedative agent
An ideal agent used to induce analgosedation should be efficacious at the used dose, which has minimum effects on the vital parameters, has a rapid offset and is associated with a low rate of adverse reactions. Desirable properties of an ideal analgesic for colonoscopy will ensure comfort to a conscious patient, which will allow for a dynamic change of patients in the endoscopic laboratory. Such an agent should have a rapid onset and short duration, exhibit analgesic and anxiolytic action, ease of titration to a desired level, rapid recovery, and an excellent safety profile with the existence of a specific, rapidly acting antagonist – all this without the need for additional personnel. Drugs used in analgosedation for colonoscopy can be classified into several groups: benzodiazepines, α2-agonists, opioids, intravenous anaesthetics and inhaled anaesthetics.
Benzodiazepines
Benzodiazepines are commonly used for sedation and induction of memory loss or as adjunct agents for general anaesthesia. They also act as anticonvulsants and muscle relaxants. Benzodiazepines enhance the inhibitory effects of GABA receptors. Their pharmacological characteristics is varied, e.g. some of them show potent sedative effects, while other have stronger anxiolytic activity.
Diazepam
Diazepam was the only agent in this group used in the early period of endoscopy and it is still used for colonoscopy worldwide. The popularity of diazepam is due to its relatively long half-life compared to newer benzodiazepines, such as midazolam. Respiratory depression is the main adverse effect of diazepam. The drug can also cause injection-site phlebitis. It is used at a single intravenous dose of 5-10 mg (17).
Midazolam
Midazolam is a short acting benzodiazepine, which is still the most commonly used sedative in colonoscopy. It is 1.5-3.5-times more potent than diazepam. The duration of action onset is 1-3 minutes, the peak effect begins after 3-4 minutes, the duration of action following a single dose is 15-80 minutes, depending on factors such as obesity, advanced age, liver and kidney diseases. Midazolam administration may occasionally induce paradoxical reactions, such as aggressive behaviour or agitation. It is usually given in a single dose of 30-50 μg/kg body weight for colonoscopy, followed by intravenous titration to reach the desired level of sedation. Dosage reduction is recommended in patients over 60 years of age (18).
Flumazenil

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Piśmiennictwo
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otrzymano: 2017-02-02
zaakceptowano do druku: 2017-02-21

Adres do korespondencji:
*Jacek Wadełek
Oddział Anestezjologii i Intensywnej Terapii Szpital Chirurgii Urazowej św. Anny w Warszawie Mazowieckie Centrum Rehabilitacji „STOCER” Sp. z o.o.
ul. Barska 16/20, 02-315 Warszawa
tel.: +48 (22) 579-52-58
WAD_jack@poczta.fm

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