The concept of preprocedural verification using a verbal “time-out” was originally developed as a patient-safety measure to prevent wrong-site surgery; however, it has evolved to become standard protocol before any medical procedure and should be performed before every procedure in the cardiac catheterization lab. The purpose of the time-out immediately before starting the procedure is to conduct a final assessment that the correct patient, site, positioning, and procedure are identified and that all relevant documents, related information, and necessary equipment are available. Each catheterization lab should have a standardized time-out protocol. The time-out should be performed prior to the introduction of local anesthesia and sedation, should be initiated by a physician operator, and all staff participating in the case (nurses, technicians, etc.) should be involved. It should involve interactive verbal communication between all team members, and any team member should be able to express concerns about the procedure verification. During the time-out, other activities are suspended, to the extent possible without compromising patient safety, so that all relevant members of the team are focused on the active confirmation of the correct patient, procedure, site, and other critical elements. All time-outs should address the topics listed in Table 2-1.

Preprocedural Sedation: In nonemergent situations, a detailed discussion with the patient and family explaining the cardiac catheterization procedure, potential complications, and alternative diagnostic options helps to alleviate any anxiety prior to the procedure. Prior to administration of preprocedural sedation, the operator should ascertain that informed consent has been obtained and that all of the patient’s questions have been answered.

The objective of preprocedural sedation is to maximize procedure safety by making the patient cooperative, calm, and relaxed. The goal should be to achieve conscious sedation: a state where the patient has a depressed level of consciousness but still maintains the independent ability to preserve a patent airway and respond appropriately and quickly to verbal and/or physical stimuli. Prior to administration of preprocedural sedation, the operator should examine the patient with special attention to the airway to identify patients who may require additional caution with the use of sedative agents (e.g., sleep apnea, laryngeal mass, intrinsic pulmonary disease).

Factors that may influence the selection and dose of sedative include the patient’s age and weight, anticipated procedure length, comorbid medical illnesses, level of anxiety, pain threshold, drug allergies, and potential drug interactions. If preprocedural sedation is initiated with oral medications, they should be administered at least 1 hour prior to the patient arriving at the catheterization laboratory. Table 2-2 lists commonly used medications for preprocedural sedation and their antagonists. A benzodiazepine is usually the initial drug of choice since it is not only a sedative and anxiolytic, but also achieves a limited degree of retrograde amnesia. Midazolam (Versed) is often the preferred choice because of its rapid onset of action and relative short duration of effect. Initial doses range from 0.5 to 1 mg IV, which may be repeated every few minutes until desired sedation is achieved. If further sedation is needed, administering a
short-acting opioid such as fentanyl (25-50 μg) often results in adequate patient comfort.

Overview of Available Contrast Agents: Iodinated contrast media are the most frequently used intravascular pharmacologic agents in the world. More than 70 million injections are administered worldwide
each year. All intravascular contrast agents contain iodine, which absorbs x-rays to a greater degree than surrounding tissue and allows for intravascular opacification. Iodine atoms are bound to carbon-based molecules, making the agent water soluble. Contrast agents are classified based on their osmolality (high, low, or iso-osmolal). High-osmolar contrast media (HOCM) were the first intravascular contrast agents developed in the 1950s. They have an osmolality five to eight times greater than that of plasma (approximately 2,000 mOsm/kg). In the 1980s, low osmolar contrast media (LOCM) were created, having an osmolality of two to three times that of plasma (600-800 mOsm/kg). Then, in the 1990s, the first iso-osmolar contrast media (IOCM), iodixanol, was developed, with an osmolality of 290 mOsm/kg. Given the substantially higher rates of adverse effects with use of HOCM, these agents are effectively obsolete and are no longer used clinically. Thus, all currently available contrast media are either LOCM or IOCM. Table 2-3 lists examples of the commonly used contrast agents used in coronary angiography.

Adverse Effects: Many of the studies that have attempted to differentiate the various adverse effects of specific LOCM have been contradictory, making it difficult to make firm recommendations for use of a particular agent. Selection of a particular LOCM varies among institutions and operators and is often made based on personal experience and preference. Some basic guidelines regarding the choice of agent will be presented in the following sections.

Effect on Myocardial Function: The degree of myocardial depression, peripheral vasodilation, and elevation of left ventricular filling pressures seen with contrast agents is more marked with agents that have higher osmolality. This is even more apparent when larger boluses of contrast agents are used during ventriculography or aortography. When HOCM
were used routinely, it was not uncommon to have peripheral vasodilation with a transient reduction in systolic blood pressure of 20 to 50 mm Hg and corresponding compensatory increase in heart rate with the use of high osmotic agents. These hemodynamic perturbations could be particularly catastrophic in patients with relatively low cardiac reserve such as left main coronary artery disease, severe aortic stenosis, or severe left ventricular dysfunction (see Chapter 7). In contrast, the LOCM used today typically only cause a reduction in systolic blood pressure of 5 to 15 mm Hg with no change in heart rate during ventriculography or aortography. Despite the more minor hemodynamic effects, caution must still be used when performing these procedures in potentially unstable patients.

Electrophysiologic Effects: Injection of contrast media into the coronary arteries can rarely cause ventricular fibrillation or sinus bradycardia, occasionally leading to transient sinus arrest. The incidence of these events is low. Series with nonionic LOCM found an incidence of 0.1% for ventricular fibrillation and 0.2% for bradycardia.

Effect on Renal Function: Contrast-induced acute kidney injury (AKI) is the most common and most serious adverse effect of intravascular contrast administration. Contrast-induced AKI is typically defined as an increase in serum creatinine of at least 0.5 mg/dL or 25% increase above baseline that occurs within the first 24 hours after contrast administration and peaks within the first 5 days. It is estimated that approximately 7% of patients receiving intravascular contrast will suffer AKI. It has been shown that these patients have up to a fivefold increase in the risk of in-hospital death over matched controls who did not develop contrast-induced AKI. Overall, less than 1% of patients who suffer contrast-induced nephropathy ultimately require chronic dialysis. Various factors (Table 2-4) may predispose a patient to deterioration in renal function after the use of contrast agents. Of these, chronic kidney disease (CKD) with reduction in estimated glomerular filtration rate (GFR)
below 60 mL/min/m² is the most significant. Patients with CKD have a reduced number of nephrons. The remaining healthy nephrons are susceptible to damage by iodinated contrast, leading to contrast-induced AKI. After intravascular administration of contrast material, the kidney responds by releasing potent renal vasoconstrictors, which reduce renal blood flow by up to 50%. The reduced blood flow leads to concentration of contrast in the renal tubules and collecting ducts, which allows for direct cellular injury and death to renal tubular cells. The degree of toxicity to tubular cells is related to the length of time the cells are exposed to contrast, high-lighting the importance of high urinary flow rates before contrast administration.

Prevention of Contrast-induced AKI: There are several strategies to reduce the risk of contrast-induced AKI in susceptible patients. Prior to contrast administration, potentially nephrotoxic drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), calcineurin inhibitors, high-dose loop diuretics, and aminoglycosides should be held for several days, if possible. In addition, volume expansion and treatment of dehydration have been shown to prevent AKI in clinical studies. There is limited data to recommend an optimal prehydration strategy, but it appears that isotonic crystalloid such as normal saline or sodium bicarbonate are more effective than half-normal saline. Despite some recent enthusiasm that isotonic bicarbonate may be superior to normal saline in the prevention of contrast-induced AKI, the largest clinical trial to date showed no clear advantage for bicarbonate over saline. There is also little data on the optimum urinary flow rate. One study found that urinary flow rate of >150 mL/hr in the 6 hours after the procedure was associated with reduced rates of AKI. To obtain this, however, isotonic crystalloid needs to be administered at 1.0 to 1.5 mL/kg/min, owing to the loss of some fluid to the interstitial space.

There are currently no approved pharmacologic agents to prevent contrast-induced AKI. Despite its popularity, N-acetylcysteine (NAC) has not been consistently shown to be effective in preventing AKI. The only treatment that has been shown to be effective is high-dose ascorbic acid. The dose used in the one prospective trial published was 3 g orally the night before contrast exposure and 2 g orally twice a day for 1 day after the procedure.

Once contrast is administered, limiting contrast volume for all patients to less than 5 mL/kg divided by the serum creatinine has been shown to be associated with lower rates of contrast-induced AKI. For patients with CKD, use of as little contrast as possible (<30 mL if possible) appears to be related to a reduction in subsequent dialysis. It should be noted, however, that even small volumes of contrast can have adverse effects on renal function in patients at high risk for AKI. For these patients, there is no safe dosing threshold below
which there is no risk of AKI. It is recommended that contrast volumes below 100 mL are preferable in patients who have an estimated GFR <60 mL/min/m².

The choice of contrast agent is also a major factor in determining the risk of contrast-induced AKI. Use of LOCM confers a significantly lower risk of AKI compared to HOCM. However, multiple trials have shown that IOCM has the lowest risk for contrast-induced AKI, especially in patients with CKD and diabetes mellitus (DM). Currently, iodixanol (Visipaque, GE Healthcare Biosciences/Amersham Health, Piscataway, NJ) is the only clinically available IOCM. An expert panel has recommended that in patients undergoing angiographic procedures with CKD with estimated glomerular filtration rate (eGFR) <60 mL/min/m², and particularly those with DM, iodixanol presents the lowest risk of contrast-induced AKI and should be the contrast agent of choice. It is also recommended that iodixanol be used in renal dialysis patients to minimize the chances of volume overload and associated complications before the next dialysis session.