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
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
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 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
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.
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 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
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.
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
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
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
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
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.
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.
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
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
Monitored anesthesia care (MAC) is a safe, effective, and appropriate form of anesthesia for many minor surgical procedures. The proliferation of outpatient procedures has heightened interest in MAC sedation agents. Among the most commonly used MAC sedation agents today are benzodiazepines, including midazolam, and propofol. Recently approved in the United States is fospropofol, a prodrug of propofol which hydrolyzes in the body by alkaline phosphatase to liberate propofol. Propofol liberated from fospropofol has unique pharmacological properties, but recently retracted pharmacokinetic (PK) and pharmacodynamic (PD) evaluations make it difficult to formulate clear conclusions with respect to fospropofol's PK/PD properties. In safety and efficacy clinical studies, fospropofol demonstrated dose-dependent sedation with good rates of success at doses of 6.5 mg/kg along with good levels of patient and physician acceptance. Fospropofol has been associated with less pain at injection site than propofol. The most commonly reported side effects with fospropofol are paresthesia and pruritus. Fospropofol is a promising new sedation agent that appears to be well suited for MAC sedation, but further studies are needed to better understand its PK/PD properties as well its appropriate clinical role in outpatient procedures.
Consideration of which pharmacologic agent to use when a patient requires sedation prior to an oral surgery procedure entails a number of factors, including past medical history, current medications and dose level, duration of administration, pharmacologic interactions, and the dental needs of the patient. The case described in this report illustrates the importance of consideration of these factors in a patient who required sedation prior to oral surgery while taking 800 mg chlorpromazine, 300 mg amantadine hydrochloride, and 900 mg of cimetidine daily. The possible pharmacologic interactions which could occur from concomitantly administering either diazepam or a narcotic in the presence of these agents are numerous and significant. The choice of sedative agent was further complicated by the fact that the patient was prescribed chlorpromazine and amantadine in doses which far exceeded the usual therapeutic levels and had been maintained for an extended period of time, over 8 months. Consequently, any adverse reactions that may have resulted when sedating a patient taking chlorapromazine and amantadine hydrochloride in lower doses for a shorter duration would be more likely to occur with greater speed and severity in a patient receiving such high-dose, long-term therapy. Also, unusual reactions which have not been reported with usual therapeutic dose levels might also occur since these high doses approach toxic levels for some patients. Additionally, a sedative agent had to be used which would not interfere with the antipsychotic effects of chlorpromazine since the patient's psychiatric condition required maintenance of these unusually high therapeutic levels. The following case report gives the rationale and outcome of utilizing nalbuphine for obtunding pain and producing sedation during an oral surgery procedure under such complex therapeutic conditions.
Objective: To review data on pharmacokinetic factors that influence the absorption and tissue distribution for individual antibiotic agents to better inform clinicians on rational dosing considerations of oral antibiotics for the treatment of acne vulgaris. The focus is placed on the most commonly prescribed oral antibiotics for acne vulgaris, the tetracyclines. Dose-response is also reviewed. Design and methods: This review describes factors affecting the absorption, distribution, and target tissue penetration of the most frequently prescribed oral antibiotics for the treatment of acne vulgaris, the tetracyclines. Articles cited were identified by a search of PubMed covering the period from January 1, 2000, to November 15, 2010. Reference lists in articles identified in this search were searched manually for additional references of interest. Results: Pharmacokinetic factors that may influence outcomes in antibiotic therapy for acne vulgaris include drug solubility, gastrointestinal permeability, systemic absorption, tissue distribution, and target tissue penetration. In particular, drugs that are highly soluble and highly permeable are well absorbed and widely distributed. Drugs that are more lipophilic are believed to penetrate better into the lipid-rich sebaceous follicular tissues, where the therapeutic target, Propionibacterium acnes, resides. Food intake and differences in patient body weight can also alter antibiotic absorption and distribution, potentially resulting in differences in efficacy and tolerability. Dose-response data with oral antibiotics, including the tetracyclines, is scant. Pharmacokinetic studies completed with extended-release minocycline have allowed for assessment of interindividual differences in drug absorption, a consideration that may influence therapeutic response and/or predilection for adverse effects. Dose-response pharmacokinetic data is not currently available with other tetracyclines. Conclusion: An understanding of the differences in absorption (with and without meals or other ingestants), distribution, and target tissue penetration among oral tetracyclines is valuable for clinicians, as such factors may influence outcomes in patients treated for acne vulgaris.
The use of dynamic electrocardiogram (ECG) monitoring is regarded as a standard of care during general anesthesia and is strongly encouraged when providing deep sedation. Although significant cardiovascular changes rarely if ever can be attributed to mild or moderate sedation techniques, the American Dental Association recommends ECG monitoring for patients with significant cardiovascular disease. The purpose of this continuing education article is to review basic principals of ECG monitoring and interpretation.
Electrocardiography; Patient monitoring; Continuing education
Sedation is often necessary to optimize care for critically ill children requiring mechanical ventilation. If too light or too deep, however, sedation can cause significant adverse reactions, making it important to assess the degree of sedation and maintain its optimal level. We evaluated the efficacy of the COMFORT scale in assessing optimal sedation in critically ill children requiring mechanical ventilation. We compared 12 month data in 21 patients (intervention group), for whom we used the pediatric intensive care unit (PICU) sedation protocol of Asan Medical Center (Seoul, Korea) and the COMFORT scale to maintain optimal sedation, with the data in 20 patients (control group) assessed before using the sedation protocol and the COMPORT scale. Compared with the control group, the intervention group showed significant decreases in the total usage of sedatives and analgesics, the duration of mechanical ventilation (11.0 days vs. 12.5 days) and PICU stay (15.0 days vs. 19.5 days), and the development of withdrawal symptoms (1 case vs. 7 cases). The total duration of sedation (8.0 days vs. 11.5 days) also tended to decrease. These findings suggest that application of protocol-based sedation with the COMPORT scale may benefit children requiring mechanical ventilation.
Sedation; Children; Mechanical Ventilation; Withdrawal; Critical Care
ERCP practically requires moderate to deep sedation controlled by a combination of benzodiazepine and opiod. Propofol as a sole agent may cause oversedation. A combination (cocktail) of infused propofol, meperidine, and midazolam can reduce the dosage of propofol and we hypothesized that it might decrease the risk of oversedation. We prospectively compare the efficacy, recovery time, patient satisfactory, and side effects between cocktail and conventional sedations in patients undergoing ERCP.
ERCP patients were randomized into 2 groups; the cocktail group (n = 103) and the controls (n = 102). For induction, a combination of 25 mg of meperidine and 2.5 mg of midazolam were administered in both groups. In the cocktail group, a bolus dose of propofol 1 mg/kg was administered and continuously infused. In the controls, 25 mg of meperidine or 2.5 mg/kg of midazolam were titrated to maintain the level of sedation.
In the cocktail group, the average administration rate of propofol was 6.2 mg/kg/hr. In the control group; average weight base dosage of meperidine and midazolam were 1.03 mg/kg and 0.12 mg/kg, respectively. Recovery times and patients’ satisfaction scores in the cocktail and control groups were 9.67 minutes and 12.89 minutes (P = 0.045), 93.1and 87.6 (P <0.001), respectively. Desaturation rates in the cocktail and conventional groups were 58.3% and 31.4% (P <0.001), respectively. All desaturations were corrected with temporary oxygen supplementation without the need for scope removal.
Cocktail sedation containing propofol provides faster recovery time and better patients’ satisfaction for patients undergoing ERCP. However, mild degree of desaturation may still develop.
Cocktail sedation containing propofol; Meperidine; Midazolam; ERCP