Moderate and deep sedation can be provided using several routes of drug administration including oral (PO), inhalation, and parental injection. The safety and efficacy of these various techniques is largely dependent on pharmacokinetic principles. This continuing education article will highlight essential principles of absorption, distribution, and elimination of commonly used sedative agents.
Pharmacokinetics; Drug administration; Sedation
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
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.
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.
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.
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 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
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.
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
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
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
Moderate to deep sedation is generally used for endoscopic retrograde cholangiopancreatography (ERCP). The depth of sedation is usually judged by clinical assessment and electroencephalography-guided monitoring. The aim of this study was to compare the clinical efficacy of clinical assessment and NarcotrendTM monitoring during deep-sedated ERCP.
One hundred patients who underwent ERCP in a single year were randomly assigned to either group C or group N. Patients in group C (52) were sedated using the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale. Patients in group N (48) were sedated using the NarcotrendTM system. The MOAA/S scale 1 or 2 and the NarcotrendTM index 47–56 to 57–64 were maintained during the procedure. The primary outcome variable of the study was the successful completion of the endoscopic procedure. The secondary outcome variables were the total dose of propofol used during the procedure, complications during and immediately after procedure, and recovery time.
All endoscopies were completed successfully. The mean total dose of propofol in group C was significantly lower than that in group N. However, the mean dose of propofol, expressed as dose/kg or dose/kg/h in both groups, was not significantly different (P = 0.497, 0.136). Recovery time, patient tolerance and satisfaction, and endoscopist satisfaction were comparable between the two groups. All sedation-related adverse events during and immediately after the procedure, such as hypotension, hypertension, tachycardia, bradycardia, transient hypoxia, and upper airway obstruction, in group C (62.2%) were significantly higher than in group N (37.5%) (P = 0.028).
Clinical assessment and NarcotrendTM-guided sedation using propofol for deep sedation demonstrated comparable propofol dose and recovery time. Both monitoring systems were equally safe and effective. However, the NarcotrendTM-guided sedation showed lower hemodynamic changes and fewer complications compared with the clinical assessment-guided sedation.
deep sedation; endoscopic retrograde cholangiopancreatography; clinical assessment; NarcotrendTM monitoring
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
A significant minority of dying people experience refractory symptoms or extreme distress unresponsive to conventional therapies. In such circumstances, sedation may be used to decrease or remove consciousness until death occurs. This practice is described in a variety of ways, including: 'palliative sedation', 'terminal sedation', 'continuous deep sedation until death', 'proportionate sedation' or 'palliative sedation to unconsciousness'. Surveys show large unexplained variation in incidence of sedation at the end of life across countries and care settings and there are ethical concerns about the use, intentions, risks and significance of the practice in palliative care. There are also questions about how to explain international variation in the use of the practice. This protocol relates to the UNBIASED study (UK Netherlands Belgium International Sedation Study), which comprises three linked studies with separate funding sources in the UK, Belgium and the Netherlands. The aims of the study are to explore decision-making surrounding the application of continuous sedation until death in contemporary clinical practice, and to understand the experiences of clinical staff and decedents' informal care-givers of the use of continuous sedation until death and their perceptions of its contribution to the dying process. The UNBIASED study is part of the European Association for Palliative Care Research Network.
To realize the study aims, a two-phase study has been designed. The study settings include: the domestic home, hospital and expert palliative care sites. Phase 1 consists of: a) focus groups with health care staff and bereaved informal care-givers; and b) a preliminary case notes review to study the range of sedation therapy provided at the end of life to cancer patients who died within a 12 week period. Phase 2 employs qualitative methods to develop 30 patient-centred case studies in each country. These involve interviews with staff and informal care-givers closely involved in the care of cancer patients who received continuous sedation until death.
To our knowledge, this is one of the few studies which seek to take a qualitative perspective on clinical decision making surrounding the use of continuous sedation until death and the only one which includes the perspectives of nurses, physicians, as well as bereaved informal care-givers. It has several potential strengths, weaknesses, opportunities and threats associated with the specific design of the study, as well as with the sensitive nature of the topic and the different frameworks for ethical review in the participating countries.
Analgesia and sedation has been widely used in intensive care units where iatrogenic discomfort often complicates patient management. In neurological patients maximal comfort without diminishing patient responsiveness is desirable. In these patients successful management of sedation and analgesia incorporates a patient based approach that includes detection and management of predisposing and causative factors, including delirium, monitoring using sedation scales, proper medication selection, emphasis on analgesia based drugs and incorporation of protocols or algorithms. So, to optimize care clinician should be familiar with the pharmacokinetic and pharmacodynamic variables that can affect the safety and efficacy of analgesics and sedatives.
Analgesia; neurocritical care; sedation
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
Allergic rhinitis (AR) is a prevalent disease with great morbidity and significant societal and economic burden. Intranasal corticosteroids are recommended as first-line therapy for patients with moderate-to-severe disease, especially when nasal congestion is a major component of symptoms. To compare the efficacy and safety profile of different available intranasal corticosteroids for the treatment of AR, it is important to understand their different structures and pharmacokinetic and pharmacodynamic properties. Knowledge of these drugs has increased tremendously over the last decade. Studies have elucidated mechanisms of action, pharmacologic properties, and the clinical impact of these drugs in allergic respiratory diseases. Although the existing intranasal corticosteroids are already highly efficient, the introduction of further improved formulations with a better efficacy/safety profile is always desired. Fluticasone furoate nasal spray is a new topical corticosteroid, with enhanced-affinity and a unique side-actuated delivery device. As it has high topical potency and low potential for systemic effects, it is a good candidate for rhinitis treatment.
fluticasone furoate; corticosteroids; rhinitis; efficacy; safety; ARIA
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
The aim of this paper is to critically discuss some of the ethically controversial issues regarding continuous deep palliative sedation at the end of life that are addressed in the EAPC recommended framework for the use of sedation in palliative care.
We argue that the EAPC framework would have benefited from taking a clearer stand on the ethically controversial issues regarding intolerable suffering and refractory symptoms and regarding the relation between continuous deep palliative sedation at the end of life and euthanasia. It is unclear what constitutes refractory symptoms and what the relationship is between refractory symptoms and intolerable suffering, which in turn makes it difficult to determine what are necessary and sufficient criteria for palliative sedation at the end of life, and why. As regards the difference between palliative sedation at the end of life and so-called slow euthanasia, the rationale behind stressing the difference is insufficiently demonstrated, e.g. due to an overlooked ambiguity in the concept of intention. It is therefore unclear when palliative sedation at the end of life amounts to abuse and why.
The EAPC framework would have benefited from taking a clearer stand on some ethically controversial issues regarding intolerable suffering and refractory symptoms and regarding the relation between continuous deep palliative sedation at the end of life and euthanasia. In this text, we identify and discuss these issues in the hope that an ensuing discussion will clarify the EAPC's standpoint.
The bispectral (BIS) index has been used to interpret partial EEG recordings to predict the level of sedation and loss of consciousness in patients undergoing general anesthesia. The author has evaluated BIS technology in determining the level of sedation in patients undergoing outpatient deep sedation. These experiences are outlined in this review article. Initially, the correlation of the BIS index with traditional subjective patient evaluation using the Observer's Assessment of Alertness and Sedation (OAA/S) scale was performed in 25 subjects. In a second study, the recovery profile of 39 patients where the BIS was used to monitor sedation was compared with a control group where the monitor was not used. A strong positive relationship between the BIS and OAA/S readings was found in the initial subjects. From the recovery study, it appears that use of the BIS monitor may help titrate the level of sedation so that less drugs are used to maintain the desired level of sedation. A trend to earlier return of motor function in BIS-monitored patients was also demonstrated. BIS technology offers an objective, ordinal means of assessing the depth of sedation. This can be invaluable in comparing studies of techniques. The BIS index provides additional information to standard monitoring techniques that helps guide the administration of sedative-hypnotic agents. The trend to earlier return of motor function in BIS-monitored patients warrants further investigation.
Endoscopic submucosal dissection (ESD) is accepted as a treatment for gastric neoplasms and usually requires deep sedation. The aim of this study was to evaluate the safety and efficacy profiles of deep sedation induced by continuous propofol infusion with or without midazolam during ESD.
A total of 135 patients scheduled for ESDs between December 2008 and June 2010 were included in this prospective study and were randomly assigned to one of two groups: the propofol group or the combination group (propofol plus midazolam).
The propofol group reported only one case of severe hypoxemia with no need of mask ventilation or intubation. Additionally, 18 cases of mild hypotension were observed in the propofol group, and 11 cases were observed in the combination group. The combination group had a lower mean total propofol dose (378 mg vs 466 mg, p<0.012), a longer mean recovery time (10.5 minutes vs 7.9 minutes, p=0.027), and a lower frequency of overall adverse events (32.8% vs 17.6%, p=0.042).
Deep sedation induced by continuous propofol infusion was shown to be safe during ESD. The combination of continuous propofol infusion and intermittent midazolam injection can decrease the total dose and infusion rate of propofol and the overall occurrence of adverse events.
Deep sedation; Propofol; Midazolam; Endoscopy; Gastrointestinal
Propofol and pentobarbital are commonly used to sedate children undergoing magnetic resonance imaging (MRI).
To compare the safety of three types of sedation: intravenous propofol (PROP), mixed pentobarbital/propofol (PENT), and mixed pentobarbital group requiring supplemental sedation (PENT SUPP) regimens in pediatric patients following deep sedation (DS) for noncardiac MRI.
Materials and Methods:
We conducted a case-control study matching 619 cases with complications with 619 controls using data from our institution's sedation database for children deeply sedated for noncardiac MRI. Cases were defined as patients with any complication and we characterized complications from cases, and used a conditional logistic regression model to assess the association between three DS methods and occurrence of complications after adjusting for confounding variables.
We found that complications occurred in association with 794 (10.1%) of the 7,839 DSs performed for MRI between 1998 and 2008. Of the 794 cases, 619 cases met inclusion criteria for the study. Among the 619 cases that met inclusion criteria, 24 (0.3% of 7,839 DSs total) were associated with major complications. Type of sedation was significantly associated with the occurrence of complications, and the PENT group was associated with decreased odds of complications when compared to the PROP regimen (OR 0.68; 95% CI 0.46, 0.98; P=0.040) and compared to the PENT SUPP group (OR 0.60; 95% CI 0.31, 0.89; P<0.0001).
DS with a pentobarbital technique was associated with decreased odds for complications when compared to a propofol-based technique or a pentobarbital technique requiring supplemental sedation.
MRI in infants and children; pediatric sedation; pentobarbital; propofol
The effect of the depth of sedation on the function of the autonomic nervous system is not well known.
To describe the effect of level of sedation on heart rate variability as a marker of the function of the autonomic nervous system in patients receiving mechanical ventilation.
This pilot study was part of a larger study in which sedation level was measured continuously for up to 24 hours. The sample consisted of 14 patients receiving mechanical ventilation. The R-R interval was measured continuously via electrocardiography. Sedation level was determined by using the Patient State Index and was categorized as deep (<60) or light (≥60). Continuous heart rate data of 5 to 10 minutes for each sedation level for each patient were analyzed.
Parasympathetic activity as indicated by root mean square of successive difference of the R-R interval, the high-frequency component, and the percentage of differences of successive N-N intervals (intervals due to normal sinus depolarization) that differed more than 50 milliseconds was significantly lower for deep sedation than for light sedation. The markers indicating sympathetic activity, including the low-frequency component and the ratio of the low-frequency component to the high-frequency component, did not differ significantly between the 2 levels of sedation. Most patients were receiving benzodiazepines.
Deep sedation may be associated with depression of parasympathetic function in patients receiving mechanical ventilation. Use of benzodiazepines most likely contributed to this finding.
Aims. (1) To assess the efficacy and safety of pediatric office-based sedation for ophthalmologic procedures using a pediatric sedation service model. (2) To assess the reduction in hospital charges of this model of care delivery compared to the operating room (OR) setting for similar procedures. Background. Sedation is used to facilitate pediatric procedures and to immobilize patients for imaging and examination. We believe that the pediatric sedation service model can be used to facilitate office-based deep sedation for brief ophthalmologic procedures and examinations. Methods. After IRB approval, all children who underwent office-based ophthalmologic procedures at our institution between January 1, 2000 and July 31, 2008 were identified using the sedation service database and the electronic health record. A comparison of hospital charges between similar procedures in the operating room was performed. Results. A total of 855 procedures were reviewed. Procedure completion rate was 100% (C.I. 99.62–100). There were no serious complications or unanticipated admissions. Our analysis showed a significant reduction in hospital charges (average of $1287 per patient) as a result of absent OR and recovery unit charges. Conclusions. Pediatric ophthalmologic minor procedures can be performed using a sedation service model with significant reductions in hospital charges.
To conduct a prospective survey in a teaching hospital emergency department to evaluate performance according to safe sedation principles, to establish the demographics of those sedated, and to review the drugs used and doses given to patients in the department. Any adverse events were reviewed for identification of preventable causes.
Pre‐sedation checklists, peri‐procedural observations, and patient notes were reviewed for 101 cases from 4 December 2004 to 3 September 2005. There are departmental guidelines outlining the principles of safe sedation.
Emergency department procedural sedation was performed for a variety of acute conditions in patients aged from 7 to 91 years old. A variety of sedation agents were administered, morphine and midazolam being used most frequently. Drug administration, maximum sedation level, and time to recovery and discharge were recorded. Four adverse events were reported, none of which were clinically significant. Departmental guidelines were followed.
Emergency department sedation is a safe and effective procedure if appropriately trained practitioners follow the principles of safe sedation.
emergency department; guidelines; sedation