Moderate and deep sedation can be provided using various classes of drugs, each having unique mechanisms of action. While drugs within a given classification share similar mechanisms and effects, certain classes demonstrate superior efficacy but added concern regarding safety. This continuing education article will highlight essential principles of pharmacodynamics and apply these to drugs commonly used to produce moderate and deep sedation.
Pharmacodynamics; Drug actions; Drug mechanisms; Sedation
The use of sedatives has established efficacy and safety for managing anxiety regarding dental treatment. This article will provide essential information regarding the pharmacology and therapeutic principles that govern the appropriate use of orally administered sedatives to provide mild sedation (anxiolysis). Dosages and protocols are intended for this purpose, not for providing moderate or deeper sedation levels.
Sedation; Anxiolysis; Oral sedation; Minimal sedation; Hypnotics; Sedatives
Nitrous oxide is the most commonly used inhalation anesthetic in dentistry and is commonly used in emergency centers and ambulatory surgery centers as well. When used alone, it is incapable of producing general anesthesia reliably, but it may be combined with other inhalation and/or intravenous agents in deep sedative/general anesthestic techniques. However, as a single agent, it has impressive safety and is excellent for providing minimal and moderate sedation for apprehensive dental patients. To gain a full appreciation of the pharmacology, physiologic influences, and proper use of nitrous oxide, one must compare it with other inhalation anesthetics. The purpose of this CE article is to provide an overview of inhalation anesthetics in general and to address nitrous oxide more specifically in comparison.
General anesthesia; Inhalation anesthetics; Nitrous oxide; Conscious sedation; Moderate sedation
Sedation and analgesia comprise an important element of unpleasant and often prolonged endoscopic retrograde cholangiopacreatography (ERCP), contributing, however, to better patient tolerance and compliance and to the reduction of injuries during the procedure due to inappropriate co-operation. Although most of the studies used a moderate level of sedation, the literature has revealed the superiority of deep sedation and general anesthesia in performing ERCP. The anesthesiologist’s presence is mandatory in these cases. A moderate sedation level for ERCP seems to be adequate for octogenarians. The sedative agent of choice for sedation in ERCP seems to be propofol due to its fast distribution and fast elimination time without a cumulative effect after infusion, resulting in shorter recovery time. Its therapeutic spectrum, however, is much narrower and therefore careful monitoring is much more demanding in order to differentiate between moderate, deep sedation and general anesthesia. Apart from conventional monitoring, capnography and Bispectral index or Narcotrend monitoring of the level of sedation seem to be useful in titrating sedatives in ERCP.
Deep sedation; Endoscopic retrograde cholangiopacreatography; Monitoring; Sedatives
Sedation plays a central role in making colonoscopy tolerable for patients and feasible for the endoscopist to perform. The array of agents used for endoscopic sedation continues to evolve. Fospropofol (FP), a prodrug of propofol with a slower pharmacokinetic profile, is currently under evaluation for use during endoscopic procedures. Preliminary data suggests that FP dosed at 6.5 mg/kg is well tolerated by most patients with perineal paresthesias being the most commonly experienced adverse effect. This article will examine the current literature on the use of FP for the sedation of patients undergoing colonoscopy, highlighting the pharmacokinetics, pharmacodynamics, risks, and common adverse events associated with the novel sedative/hypnotic.
fospropofol; Aquavan; propofol; sedation; colonoscopy
Sedation practices for gastrointestinal endoscopic (GIE) procedures vary widely in different countries depending on health system regulations and local circumstances. The goal of procedural sedation is the safe and effective control of pain and anxiety, as well as to provide an appropriate degree of memory loss or decreased awareness. Sedation-related complications in gastrointestinal endoscopy, once occurred, can lead to significant morbidity and occasional mortality in patients. The risk factors of these complications include the type, dose and mode of administration of sedative agents, as well as the patient’s age and underlying medical diseases. Complications attributed to moderate and deep sedation levels are more often associated with cardiovascular and respiratory systems. However, sedation-related complications during GIE procedures are commonly transient and of a mild degree. The risk for these complications while providing any level of sedation is greatest when caring for patients already medically compromised. Significant unwanted complications can generally be prevented by careful pre-procedure assessment and preparation, appropriate monitoring and support, as well as post-procedure management. Additionally, physicians must be prepared to manage these complications. This article will review sedation-related complications during moderate and deep sedation for GIE procedures and also address their appropriate management.
Sedation; Complication; Gastrointestinal; Endoscopy
The relative efficacy and safety of drugs and combinations used clinically in dentistry as premedicants to alleviate patient apprehension are largely unsubstantiated. To evaluate the efficacy and safety of agents used for parenteral sedation through controlled clinical trials, it is first necessary to identify which drugs, doses, and routes of administration are actually used in practice. A survey instrument was developed to characterize the drugs used clinically for anesthesia and sedation by dentists with advanced training in pain control. A random sample of 500 dentists who frequently use anesthesia and sedation in practice was selected from the Fellows of the American Dental Society of Anesthesiology. The first mailing was followed by a second mailing to nonrespondents after 30 days. The respondents report a variety of parenteral sedation techniques in combination with local anesthesia (the response categories are not mutually exclusive): nitrous oxide (64%), intravenous conscious sedation (59%), intravenous “deep” sedation (47%), and outpatient general anesthesia (27%). Drugs most commonly reported for intravenous sedation include diazepam, methohexital, midazolam, and combinations of these drugs with narcotics. A total of 82 distinct drugs and combinations was reported for intravenous sedation and anesthesia. Oral premedication and intramuscular sedation are rarely used by this group. Most general anesthesia reported is done on an outpatient basis in private practice. These results indicate that a wide variety of drugs is employed for parenteral sedation in dental practice, but the most common practice among dentists with advanced training in anesthesia is local anesthesia supplemented with intravenous sedation consisting of a benzodiazepine and an opioid or a barbiturate.
Moderate intravenous (IV) sedation combined with local anesthesia is common for outpatient oral surgery procedures. An ideal sedative agent must be safe and well tolerated by patients and practitioners. This study evaluated fospropofol, a relatively new sedative/hypnotic, in comparison to midazolam, a commonly used benzodiazepine, for IV moderate sedation during oral and maxillofacial surgery. Sixty patients were randomly assigned to either the fospropofol or the midazolam group. Each participant received 1 μg/kg of fentanyl prior to administration of the selected sedative. Those in the fospropofol group received an initial dose of 6.5 mg/kg, with 1.6 mg/kg supplemental doses as needed. Those in the midazolam group received initial doses of 0.05 mg/kg, followed by 0.02 mg/kg supplemental doses. The quality of sedation in each patient was evaluated with regard to (a) onset of sedation, maintenance, and recovery profile; (b) patient and surgeon satisfaction; and (c) hemodynamic stability and adverse effects. The fospropofol group demonstrated shorter physical recovery times than midazolam patients, taking a mean of 11.6 minutes versus 18.4 minutes for physical recovery (P = .007). Cognitive recovery comparison did not find any difference with a mean of 7.5 minutes versus 8.8 minutes between the 2 drug groups (P = .123). The fospropofol group had a higher rate of local anesthetic injection recall (90.5 vs 44.4%, P = .004). Other parameters of recall were comparable. Two adverse effects demonstrated significance, with more patients in the midazolam group experiencing tachycardia (48.2 vs 9.4%, P = .001), and more patients in the fospropofol group experiencing perineal discomfort (40.6 vs 0, P < .001). No significant difference was found in any other measures of sedation safety, maintenance, or satisfaction. Fospropofol, when administered intravenously by a dentist anesthesiologist at the indicated dose in this study, appears to be a safe, well-tolerated alternative to midazolam for intravenous moderate sedation during minor oral surgery procedures.
Fospropofol; Midazolam; Moderate sedation; Outpatient surgery; IV conscious sedation; Benzodiazepine; Propofol
The fundamental principles that govern drug therapy are often overlooked by the busy clinician. This disregard frequently results in the use of particular drugs and regimens that may be less ideal for the clinical situation being managed. By convention, these principles are categorized as pharmacokinetic and pharmacodynamic. Pharmacokinetic processes include drug absorption, distribution, biotransformation (metabolism), and elimination—essentially reflecting the influence of the body on the drug administered. These principles were addressed in the preceding issue of this journal. Pharmacodynamics deals with the actual mechanisms of action and effects a drug produces on the patient and is the topic for this continuing education article.
Drug therapy; Pharmacodynamics; Dental pharmacology
Although guidelines advise titration of palliative sedation at the end of life, in practice the depth of sedation can range from mild to deep. We investigated physicians’ considerations about the depth of continuous sedation.
We performed a qualitative study in which 54 physicians underwent semistructured interviewing about the last patient for whom they had been responsible for providing continuous palliative sedation. We also asked about their practices and general attitudes toward sedation.
We found two approaches toward the depth of continuous sedation: starting with mild sedation and only increasing the depth if necessary, and deep sedation right from the start. Physicians described similar determinants for both approaches, including titration of sedatives to the relief of refractory symptoms, patient preferences, wishes of relatives, expert advice and esthetic consequences of the sedation. However, physicians who preferred starting with mild sedation emphasized being guided by the patient’s condition and response, and physicians who preferred starting with deep sedation emphasized ensuring that relief of suffering would be maintained. Physicians who preferred each approach also expressed different perspectives about whether patient communication was important and whether waking up after sedation is started was problematic.
Physicians who choose either mild or deep sedation appear to be guided by the same objective of delivering sedation in proportion to the relief of refractory symptoms, as well as other needs of patients and their families. This suggests that proportionality should be seen as a multidimensional notion that can result in different approaches toward the depth of sedation.
The fundamental principles that govern drug therapy are often overlooked by the busy clinician. This disregard frequently results in the use of particular drugs and regimens that may be less than ideal for the clinical situation being managed. By convention, these principles are categorized as pharmacokinetic and pharmacodynamic. Pharmacokinetic processes include drug absorption, distribution, biotransformation (metabolism), and elimination, essentially reflecting the influence of the body on the drug administered. Pharmacodynamics deals with the actual mechanisms of action and the effects a drug produces on the patient. This latter topic will be addressed in a future continuing education article.
Drug therapy; Pharmacokinetics; Dental pharmacology
There is very little information about the practice of sedation in Japan. Despite the remarkable advances in dentistry, fear and anxiety continue to be significant deterrents for seeking dental services. Most dental procedures can fortunately be undertaken with the aid of sedation. A comprehensive survey of all the dental schools in Japan was carried out to determine what sedation practices were used in Japan. All 29 dental schools in Japan possessed a dedicated department of anesthesiology at the time of this survey. The survey attempted to determine the specific sedation methods (techniques, routes of administration, and agents used in sedation) as well as practices (monitoring, fasting, location, education, and fees involved in sedation). The results indicate that there was a broad range in sedation practices. The Japanese Dental Society of Anesthesiology may wish to examine the findings of this study and may wish to formulate guidelines appropriate for the practice of sedation in Japan. Others may also wish to compare their own practices with those of Japan.
This study attempted to determine if sevoflurane in oxygen inhaled via a nasal hood as a sole sedative agent would provide an appropriate level of deep sedation for outpatient third molar surgery. Twenty-four patients scheduled for third molar removal were randomly assigned to receive either nasal hood inhalation sevoflurane or an intravenous deep sedation using midazolam and fentanyl followed by a propofol infusion. In addition to measuring patient, surgeon, and dentist anesthesiologist subjective satisfaction with the technique, physiological parameters, amnesia, and psychomotor recovery were also assessed. No statistically significant difference was found between the sevoflurane and midazolam-fentanyl-propofol sedative groups in physiological parameters, degree of amnesia, reported quality of sedation, or patient willingness to again undergo a similar deep sedation. A trend toward earlier recovery in the sevoflurane group was identified. Sevoflurane can be successfully employed as a deep sedative rather than a general anesthetic for extraction of third molars in healthy subjects.
The safe sedation of patients for diagnostic or therapeutic procedures requires a combination of properly trained physicians and suitable facilities. Additionally, appropriate selection and preparation of patients, suitable sedative technique, application of drugs, adequate monitoring, and proper recovery of patients is essential. The goal of procedural sedation is the safe and effective control of pain and anxiety as well as to provide an appropriate degree of memory loss or decreased awareness. Sedation practices for gastrointestinal endoscopy (GIE) vary widely. The majority of GIE patients are ambulatory cases. Most of this procedure requires a short time. So, short acting, rapid onset drugs with little adverse effects and improved safety profiles are commonly used. The present review focuses on commonly used regimens and monitoring practices in GIE sedation. This article is to discuss the decision making process used to determine appropriate pre-sedation assessment, monitoring, drug selection, dose of sedative agents, sedation endpoint and post-sedation care. It also reviews the current status of sedation and monitoring for GIE procedures in Thailand.
Sedation; Monitoring; Gastrointestinal endoscopy; Sedatives; Analgesics
Sedation allows patients to tolerate unpleasant endoscopic procedures by relieving anxiety, discomfort, or pain. It also reduces a patient's risk of physical injury during endoscopic procedures, while providing the endoscopist with an adequate setting for a detailed examination. Sedation is therefore considered by many endoscopists to be an essential component of gastrointestinal endoscopy. Endoscopic sedation by nonanesthesiologists is a worldwide practice and has been proven effective and safe. Moderate sedation/analgesia is generally accepted as an appropriate target for sedation by nonanesthesiologists. This focused review describes the general principles of endoscopic sedation, the detailed pharmacology of sedatives and analgesics (focused on midazolam, propofol, meperidine, and fentanyl), and the multiple regimens available for use in actual practice.
Sedation; Endoscopy; Analgesia; Endoscopic sedation
Procedural sedation and analgesia (PSA) is an evolving field in pediatric emergency medicine. As new drugs breach the boundaries of anesthesia in the Pediatric Emergency Department, parents, patients, and physicians are finding new and more satisfactory methods of sedation. Short acting, rapid onset agents with little or no lingering effects and improved safety profiles are replacing archaic regimens. This article discusses the warning signs and areas of a patient's medical history that are particularly pertinent to procedural sedation and the drugs used. The necessary equipment is detailed to provide the groundwork for implementing safe sedation in children. It is important for practitioners to familiarize themselves with a select few of the PSA drugs, rather than the entire list of sedatives. Those agents most relevant to PSA in the pediatric emergency department are presented.
Analgesia; pediatric; sedation
Trichloroethylene (TCE) pharmacokinetics have been studied in experimental animals and humans for over 30 years. Compartmental and physiologically based pharmacokinetic (PBPK) models have been developed for the uptake, distribution, and metabolism of TCE and the production, distribution, metabolism, and elimination of P450-mediated metabolites of TCE. TCE is readily taken up into systemic circulation by oral and inhalation routes of exposure and is rapidly metabolized by the hepatic P450 system and to a much lesser degree, by direct conjugation with glutathione. Recent PBPK models for TCE and its metabolites have focused on the major metabolic pathway for metabolism of TCE (P450-mediated metabolic pathway). This article briefly reviews selected published compartmental and PBPK models for TCE. Trichloroacetic acid (TCA) is considered a principle metabolite responsible for TCE-induced liver cancer in mice. Liver cancer in mice was considered a critical effect by the U.S. Environmental Protection Agency for deriving the current maximum contaminant level for TCE in water. In the literature both whole blood and plasma measurements of TCA are reported in mice and humans. To reduce confusion about disparately measured and model-predicted levels of TCA in plasma and whole blood, model-predicted outcomes are compared for first-generation (plasma) and second-generation (whole blood) PBPK models published by Fisher and colleagues. Qualitatively, animals and humans metabolize TCE in a similar fashion, producing the same metabolites. Quantitatively, PBPK models for TCE and its metabolites are important tools for providing dosimetry comparisons between experimental animals and humans. TCE PBPK models can be used today to aid in crafting scientifically sound public health decisions for TCE.
Various types of sedation and analgesia technique have been used during gastrointestinal endoscopy procedures. The best methods for analgesia and sedation during gastrointestinal endoscopy are still debated. Providing an adequate regimen of sedation/analgesia might be considered an art, influencing several aspects of endoscopic procedures: the quality of the examination, the patient’s cooperation and the patient’s and physician’s satisfaction with the sedation. The properties of a model sedative agent for endoscopy would include rapid onset and offset of action, analgesic and anxiolytic effects, ease of titration to desired level of sedation, rapid recovery and an excellent safety profile. Therefore there is an impulse for development of new approaches to endoscopic sedation. This article provides an update on the methods of sedation today available and future directions in endoscopic sedation.
Gastrointestinal endoscopy; Analgesia; Sedation; Propofol
Background. Voiding cystourethrograms are distressing for children and parents. Nonpharmacological methods reduce distress. Pharmacological interventions for VCUG focus on sedation as well as analgesia, anxiolysis, and amnesia. Sedation has cost, time, and safety issues. Which agents and route should we use? Are we sure that sedation does not influence the ability to diagnose vesicoureteric reflux? Methods. Literature search of Medline, EMBASE, and the Cochrane Database. Review of
comparative studies found. Results. Seven comparative studies including two randomised controlled trials were reviewed. Midazolam given orally (0.5-0.6 mg/kg) or intranasally (0.2 mg/kg) is effective with no apparent effect on voiding dynamics. Insufficient evidence to recommend other sedating agents was found. Deeper sedating agents may interfere with voiding dynamics. Conclusion. Midazolam reduces the VCUG distress, causes amnesia, and does not appear to interfere with voiding dynamics. Midazolam combined with simple analgesia is an effective method to reduce distress to children undergoing VCUG.
We evaluated the safety and efficacy of long-term administration of dexmedetomidine in patients in the intensive care unit (ICU). Primary endpoint was the incidence of hypotension, hypertension, and bradycardia. Secondary endpoints were withdrawal symptoms, rebound effects, the duration of sedation with Richmond Agitation-Sedation Scale (RASS) ≤ 0 relative to the total infusion time of dexmedetomidine, and the dose of additional sedatives or analgesics.
Dexmedetomidine 0.2–0.7 μg/kg/h was continuously infused for maintaining RASS ≤ 0 in patients requiring sedation in the ICU. Safety and efficacy of short-term (≤24 h) and long-term (>24 h) dexmedetomidine administration were compared.
Seventy-five surgical and medical ICU patients were administered dexmedetomidine. The incidence of hypotension, hypertension, and bradycardia that occurred after 24 h (long-term) was not significantly different from that occurring within 24 h (short-term) (P = 0.546, 0.513, and 0.486, respectively). Regarding withdrawal symptoms, one event each of hypertension and headache occurred after the end of infusion, but both were mild in severity. Increases of mean arterial blood pressure and heart rate after terminating the infusion of dexmedetomidine were not associated with the increasing duration of its infusion. The ratio of duration with RASS ≤ 0 was ≥ 85 % until day 20, except day 9 (70 %) and day 10 (75 %). There was no increase in the dose of additional sedatives or analgesics after the first 24-h treatment period.
Long-term safety of dexmedetomidine compared to its use for 24 h was confirmed. Dexmedetomidine was useful to maintain an adequate sedation level (RASS ≤ 0) during long-term infusion.
Dexmedetomidine; Long term; Sedation; Intensive care unit; Withdrawal
Throughout the world there is considerable variation in the techniques used to manage anxious dental patients requiring treatment. Traditionally anxious or phobic dental patients may have been sent for general anaesthesia to allow dental treatment be undertaken. While this is still the case for the more invasive oral surgical procedures, such as wisdom teeth extraction, sedation in general dentistry is becoming more popular.
Various sedation techniques using many different anaesthetic agents have gained considerable popularity over the past 30 years. While the practice of sedating patients for dental procedures is invaluable in the management of suitably assessed patients, patient safety must always be the primary concern. Medical, dental and psychosocial considerations must be taken into account when evaluating the patient need and the patient suitability for sedation or general anaesthesia.
The regulations that govern the practice of dental sedation vary throughout the world, in particular regarding the techniques used and the training necessary for dental practitioners to sedate patients. It is necessary for medical and dental practitioners to be up to date on current practice to ensure standards of practice, competence and safety throughout our profession.
This article, the first in a two-part series, will provide information to practitioners on the practice of sedation in dentistry, the circumstances where it may be appropriate instead of general anaesthesia and the risks involved with sedation. It will also discuss the specific training and qualifications required for dental practitioners to provide sedation. The second article in this series will outline the different techniques used to administer inhalation, oral and intravenous sedation in dentistry and will focus on specific methods that are practiced.
Conscious sedation; sedation; dentistry; anaesthetic agents; fear; dental phobia; anxiolysis; access to treatment
Propofol sedation for endoscopic retrograde cholangiopancreatography (ERCP) procedures is a popular current technique that has generated controversy in the medical field. Worldwide, both anesthetic and nonanesthetic personnel administer this form of sedation. Although the American and Canadian societies of gastroenterologists have endorsed the administration of propofol by nonanesthesia personnel, the US Food and Drug Administration (FDA) has not licensed its use in this manner. There is some evidence for the safe use of propofol by nonanesthetic personnel in patients undergoing endoscopy procedures, but there are few randomized trials addressing the safety and efficacy of propofol in patients undergoing ERCP procedures. A serious possible consequence of propofol sedation in patients is that it may result in rapid and unpredictable progression from deep sedation to general anesthesia, and skilled airway support may be required as a rescue measure. Potential complications following deep propofol sedation include hypoxemia and hypotension. Propofol sedation for ERCP procedures is an area of clinical practice where discussion and mutual cooperation between anesthesia and nonanesthesia personnel may enhance patient safety.
This case involves a possible complication of excessive bleeding or rupture of hemangiomas. Problems and anesthetic management of the patient are discussed. A 35-year-old man with Sturge-Weber syndrome was to undergo teeth extraction and gingivectomy. Hemangiomas covered his face and the inside of the oral cavity. We used intravenous conscious sedation with propofol and N2O-O2 to reduce the patient's emotional stress. It was previously determined that stress caused marked expansion of this patient's hemangiomas. Periodontal ligament injection was chosen as the local anesthesia technique. Teeth were extracted without excessive bleeding or rupture of hemangiomas, but the planned gingivectomies were cancelled. Deep sedation requiring airway manipulation should be avoided because there are possible difficulties in airway maintenance. Because this was an outpatient procedure, propofol was selected as the sedative agent primarily because of its rapid onset and equally rapid recovery. Periodontal ligament injection with 2% lidocaine containing 1 : 80,000 epinephrine was chosen for local anesthesia. Gingivectomy was cancelled because hemostasis was challenging. As part of preoperative preparation, equipment for prompt intubation was available in case of rupture of the hemangiomas. The typically seen elevation of blood pressure was suppressed under propofol sedation so that expansion of the hemangiomas and significant intraoperative bleeding was prevented. Periodontal ligament injection as a local anesthetic also prevented bleeding from the injection site.
Sturge-Weber syndrome; Hemangioma; Mental retardation; Anesthetic management; Oral surgery
In adult patients who are critically ill and mechanically ventilated, daily interruption of sedation (DSI) is an effective method of improving sedation management, resulting in a decrease of the duration of mechanical ventilation, the length of stay in the intensive care unit (ICU) and the length of stay in the hospital. It is a safe and effective approach and is common practice in adult ICUs. For critically ill children it is unknown if DSI is effective and feasible. The aim of this multicenter randomized controlled trial is to evaluate the safety and efficacy of daily sedation interruption in critically ill children.
Children between 0 and 18 years of age who require mechanical ventilation, with an expected duration of at least 48 h and need for sedative infusion, will be included. After enrollment patients will be randomly assigned to DSI in combination with protocolized sedation (intervention group) or protocolized continuous sedation (control group). A sedation protocol that contains an algorithm for increasing and weaning of sedatives and analgesics will be used. The sedative infusion will be restarted if the patient becomes uncomfortable or agitated according to the sedation protocol. The primary endpoint is the number of ventilator-free days at 28 days.
Pediatrics; Critical illness; Sedation; Daily sedation interruption
Complex medical procedures requiring the administration of sedation and analgesia are frequently performed in sites outside the operating room. In particular, interventional radiologists must understand basic principles of sedation and analgesia to direct nurses or nurse practitioners to provide adequate conscious sedation. The purpose of this article is to review basic principles of sedation, pharmacologic agents used for sedation and analgesia, practice guidelines, monitoring, and management of common hemodynamic problems encountered during sedation.
Sedation; analgesia; practice guidelines; nonanesthesiologist