Anesthesia for Bedside Procedures

Mark Dershwitz

When a patient in an intensive care unit (ICU) requires a bedside procedure, it is usually the attending intensivist, as opposed to a consultant anesthesiologist, who directs the administration of the necessary hypnotic, analgesic, and/or paralytic drugs. Furthermore, unlike in the operating room, the ICU usually has no equipment for the administration of gaseous (e.g., nitrous oxide) or volatile (e.g., isoflurane) anesthetics. Anesthesia for bedside procedures in the ICU is thus accomplished via a technique involving total intravenous anesthesia (TIVA).

Common Pain Management Problems in ICU Patients

Dosing of Agent

Selecting the proper dose of an analgesic to administer is problematic for several reasons, including difficulty in assessing the effectiveness of pain relief, pharmacokinetic (PK) differences
between the critically ill and other patients, and normal physiologic changes associated with aging.

Assessing the Effectiveness of Pain Relief

Critically ill patients are often incapable of communicating their feelings because of delirium, obtundation, or endotracheal intubation. This makes psychologic evaluation quite difficult because surrogate markers of pain intensity (e.g., tachycardia, hypertension, and diaphoresis) are inherent in the host response to critical illness.

Pharmacokinetic Considerations

Most of the pressors and vasodilators administered in the ICU by continuous intravenous (IV) infusion have a relatively straightforward PK behavior: they are water-soluble molecules that are bound very little to plasma proteins. In contrast, the hypnotics and opioids used in TIVA have high lipid solubility and most are extensively bound to plasma proteins, causing their PK behavior to be far more complex. Figure 20.1 shows the disappearance curves of fentanyl and nitroprusside after bolus injection. The fentanyl curve has three phases: (i) a very rapid phase (with a half-life of 0.82 minutes) lasting about 10 minutes, during which the plasma concentration decreases more than 90% from its peak value; (ii) an intermediate phase (with a half-life of 17 minutes) lasting from about 10 minutes to an hour; and (iii) finally a terminal, very slow phase (with a half-life of 465 minutes) beginning about an hour after bolus injection. After a single bolus injection of fentanyl, the terminal phase occurs at plasma concentrations below which there is a pharmacologic effect. However, after multiple bolus injections or a continuous infusion, this latter phase occurs at therapeutic plasma concentrations. Thus, fentanyl behaves as a short-acting drug after a single bolus injection, but as a very long-lasting drug after a continuous infusion of more than an hour in duration (i.e., fentanyl accumulates). Thus, it is inappropriate to speak of the half-life of fentanyl.

The disappearance curve of nitroprusside has two phases: (i) a very rapid phase (with a half-life of 0.89 minute) lasting about 10 minutes, during which the plasma concentration decreases more than 85% from its peak value, and (ii) a terminal phase (with a half-life of 14 minutes). It may be slightly slower in offset as compared with fentanyl during the initial 10 minutes after a bolus injection, but it does not accumulate at all even after a prolonged infusion.

The PK behavior of the lipid-soluble hypnotics and analgesics given by infusion may be described by their context-sensitive half-times (CSHTs). This concept may be defined as follows: when a drug is given as an IV bolus followed by an IV infusion designed to maintain a constant plasma drug concentration, the time required for the plasma concentration to fall by 50% after termination of the infusion is the CSHT [3]. Figure 20.2 depicts the CSHT curves for the medications most likely to be used for TIVA in ICU patients.

Figure 20.1. The time courses, on a semilogarithmic scale, of the plasma concentrations of fentanyl [1] and nitroprusside [2] following a bolus injection. Each concentration is expressed as the percentage of the peak plasma concentration. The fentanyl curve has three phases with half-lives of 0.82, 17, and 465 minutes. The nitroprusside curve has two phases with half-lives of 0.89 and 14 minutes.

Figure 20.2. The context-sensitive half-times for propofol [4], midazolam [5], sufentanil [6], and remifentanil [7] as a function of infusion duration.

PK behavior in critically ill patients is unlike that in normal subjects for several reasons. Because ICU patients frequently have renal and/or hepatic dysfunction, drug excretion is significantly impaired. Hypoalbuminemia, common in critical illness, decreases protein binding and increases free drug concentration [8]. Because free drug is the only moiety available to tissue receptors, decreased protein binding increases the pharmacologic effect for a given plasma concentration. It is therefore more important in ICU patients that the doses of medications used for TIVA are individualized for a particular patient.

Physiologic Changes Associated with Aging

People 65 years of age and older comprise the fastest growing segment of the population and constitute the majority of patients in many ICUs. Aging leads to (a) a decrease in total body water and lean body mass; (b) an increase in body fat and, hence, an increase in the volume of distribution of lipid-soluble drugs; and (c) a decrease in drug clearance rates, due to reductions in liver mass, hepatic enzyme activity, liver blood flow, and renal excretory function. There is a progressive, age-dependent increase in pain relief and electroencephalographic suppression among elderly patients receiving the same dose of opioid as younger patients. There is also an increase in central nervous system (CNS) depression in elderly patients following administration of identical doses of benzodiazepines.

Selection of Agent

Procedures performed in ICUs today (Table 20.1) span a spectrum that extends from those associated with mild discomfort (e.g., esophagogastroscopy) to those that are quite painful (e.g., orthopedic manipulations, wound debridement, and tracheostomy). Depending on their technical difficulty, these procedures can last from minutes to hours. To provide a proper anesthetic, medications should be selected according to the nature of the procedure and titrated according to the patient’s response to surgical stimulus. In addition, specific disease states should be considered in order to maximize safety and effectiveness.

Table 20.1 Bedside Procedures and Associated Levels of Discomfort

Mildly to moderately uncomfortable
   Transesophageal echocardiography^a
   Transtracheal aspiration
   Thoracentesis^a
   Paracentesis^a
Moderately to severely uncomfortable
   Endotracheal intubation^a
   Flexible bronchoscopy^a
   Thoracostomy^a
   Bone marrow biopsy
   Colonoscopy
   Peritoneal dialysis catheter insertion^a
   Peritoneal lavage^a
   Percutaneous gastrostomy^a
   Percutaneous intra-aortic balloon insertion^a
Extremely painful
   Rigid bronchoscopy
   Debridement of open wounds
   Dressing changes
   Orthopedic manipulations
   Tracheostomy^a
   Pericardiocentesis/pericardial window^a
   Open lung biopsy
   Ventriculostomy^a

^aProcedures in which the level of discomfort may be significantly mitigated by the use of local anesthesia.

Head Trauma

Head-injured patients require a technique that provides effective, yet brief, anesthesia so that the capacity to assess neurologic status is not lost for extended periods of time. In addition, the technique must not adversely affect cerebral perfusion pressure. If the effects of the anesthetics dissipate too rapidly, episodes of agitation and increased intracranial pressure (ICP) may occur that jeopardize cerebral perfusion. In contrast, if the medications last too long, there may be difficulty in making an adequate neurologic assessment following the procedure.

Coronary Artery Disease

Postoperative myocardial ischemia following cardiac and noncardiac surgery strongly predicts adverse outcome [9]. Accordingly, sufficient analgesia should be provided during and after invasive procedures to reduce plasma catecholamine and stress hormone levels.

Table 20.2 Characteristics of Intravenous Hypnotic Agents^a

	Propofol	Etomidate	Ketamine	Midazolam	Fospropofol
Onset	Fast	Fast	Fast	Intermediate	Intermediate
Duration	Short	Short	Intermediate	Intermediate	Short
Cardiovascular effects	↓	None	↑	Minimal	↓
Respiratory effects	↓	↓	Minimal	↓	↓
Analgesia	None	None	Profound	None	None
Amnesia	Mild	Mild	Profound	Profound	Mild
^aThe listed doses should be reduced 50% in elderly patients. Entries in bold type indicate noteworthy differences among the drugs.

Renal and/or Hepatic Failure

Risk of an adverse drug reaction is at least three times higher in patients with azotemia than in those with normal renal function. This risk is magnified by excessive unbound drug or drug metabolite(s) in the circulation and changes in the target tissue(s) induced by the uremic state.

Liver failure alters many drug volumes of distribution by impairing synthesis of the two major plasma-binding proteins: albumin and α₁-acid glycoprotein. In addition, reductions in hepatic blood flow and hepatic enzymatic activity decrease drug clearance rates.

Characteristics of Specific Agents Used for Bedside Procedures

Hypnotics

The characteristics of the hypnotics are provided in Table 20.2, whereas their recommended doses are provided in Table 20.3. When rapid awakening is desired, propofol and etomidate are the hypnotic agents of choice. Ketamine may be useful when a longer duration of anesthesia is needed. Midazolam is rarely used alone as a hypnotic; however, its profound anxiolytic and amnestic effects render it useful in combination with other agents.

Propofol

Description

Propofol is a hypnotic agent associated with pleasant emergence and little hangover. It has essentially replaced thiopental for induction of anesthesia, especially in outpatients. It is extremely popular because it is readily titratable and has more rapid onset and offset kinetics than midazolam. Thus, patients emerge from anesthesia more rapidly after propofol than after midazolam, a factor that may make propofol the preferred agent for sedation and hypnosis in general and for patients with altered level of consciousness in particular.

The CSHT for propofol is about 10 minutes following a 1-hour infusion, and the CSHT increases about 5 minutes for each additional hour of infusion for the first several hours, as shown in Figure 20.2. Thus, the CSHT is about 20 minutes after a 3-hour infusion. The CSHT rises much more slowly for infusions longer than a day; a patient who is sedated (but not rendered unconscious) with propofol for 2 weeks recovers in approximately 3 hours [10]. This rapid recovery of neurologic status makes propofol a good sedative in ICU patients,
especially those with head trauma, who may not tolerate mechanical ventilation without pharmacologic sedation.

Table 20.3 Usual Doses of Intravenous Anesthetic Agents Given by Continuous Infusion^a

	Propofol	Etomidate	Ketamine	Midazolam	Sufentanil	Remifentanil
Bolus dose (mg/kg)	1–2	0.2–0.3	1–2	0.05–0.15	0.5–1.5	0.5–1.5
Infusion rate (μg/kg/min)	100–200	NR^b	25–100	0.25–1.5	0.01–0.03	0.05–0.5
^aThe “usual doses” are for patients without preexisting tolerance and significant cardiovascular disease. The required doses will be higher in patients with tolerance, and should be reduced in elderly patients and in patients with decreased cardiovascular function. In all cases, the medications should be titrated to specific endpoints as described in the text. ^bNot recommended due to the possibility of prolonged adrenal suppression.