Intravenous Anesthesia and Sedation Outside the Operating Room

Acknowledgment

Anil Gupta would like to thank the Department of Anaesthetics, Gisborne Hospital, Gisborne, New Zealand, for the time he was given during the nonclinical sessions, which gave him the opportunity to complete this chapter.

The operating room is considered to be the most expensive part of the hospital, and therefore only procedures that require specific surgical care of the patient or dedicated anesthesia resources and postoperative care should be performed in this environment. Business managers in particular are not keen on using expensive operating room resources when a procedure can be performed under local anesthesia or during sedation and analgesia without the need for anesthesiologists. Such procedures should, whenever possible, be performed outside the operating room environment. Over the years, a disparity has existed between resources available and production targets, and demands to increase theater efficiency have therefore increased. Patient demands to provide good sedation and analgesia have simultaneously increased. As doctors, we are forced to meet the requests made by patients while ensuring safety and providing high-quality care at lower costs. These factors have created the need for providing competent anesthesia care outside the operating room at virtually no increased total costs to the health care provider. Thus the environment is ripe for creating optimal patient management systems in a non–operating room anesthesia (NORA) environment at similar or reduced costs and providing safe care with increased patient satisfaction. No business environment within the health care sector has faced so many conflicting challenges, all at the same time, in the last decade.

Coupled with the issues around safe management at reduced costs outside the operating room is the challenge to provide satisfactory conditions for surgeons, physicians, and radiologists to be able to perform the procedure in a satisfactory way and subsequently discharge the patient home as soon as possible, preferably without using postanesthesia care unit (PACU) resources. Additionally, not only do patients want to be discharged home safely but they also want participate in decision-making, drive without being injured or injuring others, take care of their children at home, and often go back to work later the same day. Although many of these demands cannot always be fulfilled, careful planning and availability of short-acting intravenous drugs with minimal side effects has made the impossible now seem achievable. To contain costs, however, several facilities have resorted to using the services of non–anesthesia-trained personnel to achieve the goal of providing sedation or analgesia in a safe way. Under these circumstances, and with the added complexity of multiple comorbidities in an increasingly aged population, supervision by a trained anesthesiologist has become increasingly important when performing procedures outside the operating room environment. Clinical practices that best achieve the goals of safety, ease of management, and safe discharge after sedation and analgesia have become a hot topic for regular discussions in corridors and conference among doctors, nurses, and health care managers, as well as the subject of increasing scientific publications in peer-reviewed journals throughout the world.

From an anesthesiology perspective, it is essential that the care given to patients undergoing procedures outside the operating room under sedation is, above all, safe. Compromising safety above costs is not acceptable practice for doctors or nurses. A team of competent and trained staff is thus needed to offer safe care at affordable costs and with full patient satisfaction. In hospitals, most guidelines on sedation and analgesia outside the operating room are today made keeping in mind the availability of competent, informed, and educated personnel. However, it is impossible to extend the use the guidelines published in one country or hospital to other countries, because of differences in the availability of drugs, monitoring standards, staff education and competence, and restriction on administration of drugs, among other factors. Therefore local practices and personnel competence should be considered when making recommendations for safe practice in sedation or analgesia techniques within each country and hospital. For instance, whereas only anesthesiologists in Australia and New Zealand can administer propofol, in Scandinavia, anesthesia nurses may administer propofol under the supervision of anesthesiologists but not surgeons. Thus it is important to take into consideration local governance, practices, and recommendations pertaining to the use of drugs by competent persons trained in the safe use of these drugs.

This chapter aims to provide alternatives for the practice of safe sedation and anesthesia outside the operating room. The focus is on total intravenous anesthesia (TIVA) as the method of choice, the drugs commonly used, and their pharmacology and side effects, but brief summary of an inhalational anesthetic as an alternative has been mentioned. Furthermore, the monitoring standards that should be used during TIVA are discussed, as well as specific patient scenarios. Details on procedure-related issues are adequately and more extensively covered in other chapters. This chapter focuses on the essentials of TIVA instead of details in the management of patients with coexisting morbidities in complex environments. The reader is referred to further reading in other chapters in this book and more specialized textbooks when dealing with patients with comorbidities.

Although anesthesia can probably be achieved equally well outside the operating room environment using inhalational anesthetics, this may not be appropriate for several reasons. For instance, procedural sedation has been described using nitrous oxide in children. However, the use of inhalational or gaseous anesthetics requires a dedicated anesthesia machine and scavenging systems, which not only add significantly to the hospital costs but may also be detrimental to the non–operating room environment. Additionally, to achieve adequate sedation using inhalation agents, personnel within the room would certainly be exposed to the potential harmful effect of these agents unless an endotracheal tube or laryngeal mask airway (LMA) device is used. These require a significantly deeper level of sedation anesthesia, with its attendant problems. A major feature and benefit of intravenous sedation and analgesia technique is the elegant and comfortable option (for both patient and anesthetist) in the smooth transition from being fully awake to anxiolysis through light sedation, deep sedation, and, if needed, general anesthesia. Another major feature with total intravenous techniques is the concept of separating the different components of sedation and anesthesia and analgesia in a tailored and independent manner. To handle such smooth transitions of the level of sedation and anesthesia while providing excellent quality for patients and with maximal safety, qualified anesthesia personnel are often needed. Compromised airway, apnea, or cardiovascular problems may occur unpredictably and must be dealt with immediately and adequately by competent personnel.

Sedation, Sedation and Analgesia, and Anesthesia

A clear difference needs to be made at the outset between the different levels of sedation (effect of drug dose) and the different quality of sedation (effect of drug choice) that should be achieved in the individual case and for a specific procedure. The level of sedation may be differentiated into light sedation, moderate sedation, and deep sedation ( Table 7-1 ), and the quality of sedation may be differentiated into anxiolysis, hypnosis (from sleepy to unconscious), and amnesia. To each of these components, analgesia may be added during painful procedures. Several scores for the assessment of the level of sedation have been described, but the ones commonly used include the Ramsay Sedation Scale ( Table 7-2 ) and the Modified Observer’s Assessment of Alertness/Sedation Scale ( Table 7-3 ). The choice of scale that should be used depends on local education, trends, and practices, but it is important to regularly and routinely register the level of sedation. It is usually helpful to make a plan together with the operator before starting the procedure as to what levels and qualities of sedation are needed and expected for a particular patient and the specific procedure. The plan may subsequently need to be adjusted during the procedure, depending on the patient’s actual response, the course of the planned intervention, and the side effects of the drugs used. Many procedures require anxiolytic and/or hypnotic effect alone because no associated pain occurs, whereas others require predominantly analgesia, with the procedure being painful but not necessarily perceived as uncomfortable or frightening to the patient. However, most procedures require a combination of anxiolysis, hypnosis, and analgesia, and the spectrum of effects ranges from predominant anxiolysis or sleep to predominant analgesia. Individual patient-, operator-, and procedure-related needs may differ; therefore it is important to inform the patient before the procedure what should be expected. Thus a radiological investigation such as magnetic resonance imaging often requires only anxiolysis or minimal sedation but no analgesia while extracorporeal shock wave lithotripsy requires predominantly analgesia with anxiolysis or minimal sedation. Gastroscopy requires predominantly sedation and anxiolysis but not pain relief, because the procedure is uncomfortable but usually not painful, whereas colonoscopy may require a combination of good analgesia, anxiolysis, and minimal sedation. Although it may be easier to provide only sedation or analgesia, the combination of both sedation (adequate and individually tailored) and analgesia (optimal, without respiratory depression) is challenging because it requires a balance between adequate (not deep) sedation and optimal (not excessive) analgesia. sedation that is too deep may result in loss of free airway and protective reflexes, and the excessive use of opioid analgesics may lead to respiratory depression. Therefore incorrect use of either of these may sometimes have major adverse effects, especially when combined and given in excessive doses. The need to maintain a free airway and assisted ventilation is unpredictable and can sometimes lead to a disaster when performed by personnel without anesthetic training and in an unfriendly and remote environment. In addition to the problems of maintaining adequate and optimal sedation and analgesia, the remote, sometimes dark working environment is also conducive to injury. Competent help is not immediately available in these circumstances, and instruments, drugs, and devices are not always readily accessible, which delays quick and adequate management and thereby compromises patient safety.

Table 7-1

American Society of Anesthesiologists Definitions of General Anesthesia and Levels of Sedation and Analgesia

From American Society of Anesthesiologists. ASA standards, guidelines and statements, October 2007. http://www.asahq.org/publications/p-106-asa-standards-guidelines-and-statements.aspx .

Evaluation Factors	Minimal Sedation (Anxiolysis)	Moderate Sedation/Analgesia (“Conscious Sedation”)	Deep Sedation/Analgesia
Responsiveness	Normal response to verbal stimulation	Purposeful ^∗ response to verbal or tactile stimulation	Purposeful response ^∗ following repeated or painful stimulation
Airway	Unaffected	No intervention required	Intervention may be required
Spontaneous ventilation	Unaffected	Adequate	May be inadequate
Cardiovascular function	Unaffected	Usually maintained	Usually maintained

∗ Reflex withdrawal from a painful stimulus is not considered a purposeful response.

Table 7-2

Ramsay Sedation Scale

From Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxalone-alphadolone. Br Med J. 1974;2(5920):656-659.

Score	Response
1	Anxious, restless, or both
2	Cooperative, oriented, and tranquil
3	Responding to commands
4	Brisk response to light glabellar tap or loud auditory stimulus
5	Sluggish response to light glabellar tap or loud auditory stimulus
6	No response to stimulus

Table 7-3

Modified Observer’s Assessment of Alertness/Sedation Scale

From Cohen LB, DeLegge MH, Aisenberg J, et al. AGA Institute review of endoscopic sedation. Gastroenterology. 2007;133(2):675-701.

Responsiveness	Score
Agitated	6
Responds readily to name spoken in normal tone (alert)	5
Lethargic response to name spoken in normal tone	4
Responds only after name is called loudly and/or repeatedly	3
Responds only after mild prodding or shaking	2
Does not respond to mild prodding or shaking	1

Finally, the correct balance between sedation and analgesia is not only a science but also an art, requiring good education and judgment combined with many years of training and experience, to achieve the correct drug dosing for individual patient needs. Sedation and analgesia are more than a cookbook recipe that can be applied to all patients in all circumstances. They require education, training, regular auditing of practice, and continuous quality improvement.

Drugs Used for Sedation and Anesthesia

This section is not expected to replace a thorough, systematic knowledge of indications, contraindications, and dosing of drugs, which can be obtained from a manual or textbook on pharmacology and anesthesia.

Inhalational Agents

Although inhalation anesthesia is used frequently for induction and maintenance of general anesthesia, it is rarely used today for sedation outside the operating room, except possibly during procedural sedation using nitrous oxide in children and laboring women. Inhalational agents should be used only in places where an appropriate scavenging system is present. However, they may occasionally be used for a short period in a well-ventilated room without a scavenging system with an appropriate indication, such as a child not accepting intravenous induction or for treating uncontrolled bronchospasm. When using inhalation agents, end-tidal gas monitoring is mandatory if low-flow systems are used but may not be necessary for occasional use of inhalational agents in high-flow systems. Sevoflurane is today recommended as the routine inhalation agent because of its low risk for airway irritation and minimal pungency. Nitrous oxide is less potent and possibly also associated with nausea and vomiting, similar to other inhalational agents. It has some advantages, including a rapid on-off effect, minimal effect on ventilation and circulation, and a reduction in the consumption of other drugs by 20% to 40% percent. It is often used for procedural sedation in children. Desflurane may be useful for maintenance of anesthesia because of its lower tissue solubility and consequently more rapid recovery in prolonged cases and in the obese, in contrast to sevoflurane. Other inhalation agents are seldom used today.

Clinical Pharmacology of Intravenous Anesthetics and Analgesics

Intravenous Hypnotics

The barbiturates (thiopentone and methohexitone) are rarely used in modern ambulatory anesthesia, but they are a low-cost alternative to propofol.

Thiopentone should be used only for induction of anesthesia or if the procedure is of very short duration, because its elimination half-life is very long. Some anesthetists and psychiatrists prefer this drug or its short-acting counterpart, methohexitone, for electroconvulsive therapy (ECT) because the seizures seen (intermittent myotonic contractions) are more evident than with propofol. Others argue that the routine use of electroencephalography to monitor seizures is the key to a successful ECT rather than the muscle contractions.

Methohexitone is fairly rapidly cleared and eliminated and also has been used during TIVA by intermittent injection, but after the introduction of propofol, it is not commonly used today, except during ECT. One disadvantage of methohexital is that many patients may have involuntary movements and hiccups during induction.

The benzodiazepines that have been commonly used for sedation and anxiolysis during ambulatory procedures include diazepam and midazolam.

Diazepam has a long elimination half-life and active metabolites, and it appears to be less hypnotic and possibly more anxiolytic than midazolam. It is a good choice for premedication, when given orally, especially if the patient needs an anxiolytic for some time before the procedure. It is seldom used today for sedation by anesthesiologists but is popular among some surgeons.

Midazolam is a hypnotic, anxiolytic, and amnesic. It is a short-acting benzodiazepine with no active metabolites. When it is given in low doses, most patients are fully awake and amnesic for a period of 30 minutes to 2 hours. It is often used as a sedative and anxiolytic by surgeons during procedures not associated with pain or in combination with analgesics when pain is anticipated. When midazolam is used in low doses, patients usually can maintain a free airway with adequate ventilation during short procedures. It is sometimes used for coinduction as part of the intravenous induction of anesthesia, but a small dose of propofol will have a similar effect without the risk for a longer recovery time.

Propofol is the gold standard hypnotic anesthetic for ambulatory surgery. In low doses it has anxiolytic, amnesic, and antiemetic properties and is also the drug of choice for sedation. Propofol is rapidly metabolized and has a high clearance, which is associated with rapid recovery. However, emergence from anesthesia after propofol infusion may be delayed unless the dose is carefully reduced toward the end of anesthesia. Recovery from propofol sedation and anesthesia is seen to be pleasant, with many patients being slightly euphoric. The antiemetic effect is an advantage, and the incidence of shivering is low. Propofol has the disadvantage that mild pain may occur when it is injected into thin veins. This can be reduced by using propofol with medium-chain triglyceride solute, using a 5-mg/mL solution instead of the 10 mg/mL, injecting 2 to 3 mL of lidocaine (10 mg/mL) or opioid before induction of sedation or anesthesia with propofol, or by mixing lidocaine 10 mg/mL, 1 mL into each 10 mL of propofol shortly before injection. It has also been shown that using a local anesthesia pad (e.g., lidocaine and prilocaine [EMLA]) may further reduce the incidence of pain from propofol injection.

Dexmedetomidine is a highly selective alpha-2 adrenoreceptor agonist with both sedative and analgesic effect and only minor respiratory depression. The sleep induced by dexmedetomidine is more like physiologic sleep (deep non-REM sleep) in that patients may be very clearheaded soon after emergence. It also has the advantage of some analgesic effect, and, unless it is used in high doses, patients can maintain a clear airway without significant respiratory depression. It has been used successfully for premedication in children and during management of patients in the intensive care unit. Several studies have been published recently in which dexmedetomidine has been used for sedation during ambulatory surgery, but its role needs to be better elucidated before it can be recommended for routine use. Although attractive as an alternative to propofol, it seems to have a slower onset and offset, which may not be ideal in the ambulatory setting.

Ketamine is an N -methyl- d -aspartate (NMDA) receptor blocker with dose-dependent analgesic, hypnotic, and some muscle relaxation effects in high doses, with retained spontaneous respiration. In contrast to other general anesthetics, ketamine stimulates the sympathetic nervous system and thus blood pressure is maintained and heart rate increased during anesthesia. One major problem with ketamine is the high incidence of nightmares and hallucinations during emergence, which may be partly counteracted by a concomitant benzodiazepine administration. Because of the side effects experienced by patients, its use in ambulatory surgery is limited in most places. Although ketamine is associated with slower emergence and some incidence of unpleasant nightmares, Friedberg reported a high success rate for sedation during plastic surgery under local anesthesia. In these studies, propofol, when supplemented by ketamine during sedation, caused no hallucinations and virtually no postoperative nausea and vomiting (PONV) despite retaining spontaneous ventilation. Although some studies in the ambulatory setting support this conclusion, Aouad et al reported a greater incidence of agitation, Goel et al reported delayed recovery, and a review by Slavik et al concluded this technique had no specific benefits. Thus ketamine, in a dose of 5 to 20 mcg/kg/min, may be a promising alternative to low-dose opioids as an adjunct to propofol sedation with safe, spontaneous ventilation in the patient with unstable cardiovascular disease, but with some side effects that limit its routine use.

Opioids

Fentanyl is a short-acting analgesic with an onset time of 2 to 4 minutes and effect duration of less than 45 minutes. It is usually administered in incremental doses of 1 to 2 mcg/kg. When used in higher doses, it may result in prolonged emergence and thus more PONV. It is useful for ambulatory procedures of short to intermediate duration if the total dose is kept low. With a single dose of fentanyl 0.05 to 0.1 mg alone (without any sedatives) in the adult patient, spontaneous ventilation is usually maintained, but respiratory frequency could be reduced. Fentanyl may be used for postprocedural pain in the ambulatory surgical patient.

Alfentanil is an alternative to fentanyl for short cases and for managing intense, short-duration nociceptive stimuli. Alfentanil has a peak effect after 2 to 3 minutes, which declines after 10 to 15 minutes. Incremental doses of 0.25 to 0.5 mg in adults (10 to 20 mcg/kg in children) are effective for short procedures. Alfentanil has a rapid onset of action; therefore it may cause chest rigidity in higher doses, specifically when hypnotics are not given first.

Remifentanil is in many ways the ideal opioid for ambulatory surgery, with a rapid peak effect within 1 to 2 minutes, and 50% recovery occurs within 3 to 4 minutes after termination of infusion. Similar to the case with alfentanil, the anesthetist should be aware of the risk for chest wall rigidity with any dose exceeding 1 mcg/kg given rapidly, with the elderly being more prone to this complication. In addition, concern exists about postoperative hyperalgesia when using remifentanil during surgery, specifically when used in higher doses. It is therefore important to ensure adequate analgesia from nonopioids and, if needed, a small dose of longer acting opioids (e.g., fentanyl 1 mcg/kg) when a remifentanil infusion is terminated.

Sufentanil is fairly similar to fentanyl during ambulatory care, but has a slightly slower onset of action and no specific advantages over other short-acting opioids for use in this setting.

Oxycodone is the opioid with the highest and most predictable bioavailability (70% to 80%) after oral dosing. Oxycodone also may be used intravenously and is probably slightly more potent (25% to 50%) than morphine. Some studies suggest that oxycodone has a lower sedative effect than morphine and is possibly better for management of visceral pain because of its greater effect on kappa receptors.

Nonopioid analgesics may be valuable when given before or at the start of anesthesia or sedation to reduce the need for stronger analgesics perioperatively, specifically in the ambulatory setting. This may in turn reduce the incidence of the PONV that is common after administration of opioids. The cornerstones of nonopioid pain therapy include paracetamol, nonsteroidal antiinflammatory drugs (NSAIDs) or coxibs, and glucocorticoid, as well as local anesthetics injected into the wounds. For further discussion, the reader is referred to specialized textbooks for the management of postoperative pain.

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