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Opioids can be administered as the primary or sole anesthetic in opioid-based anesthetic techniques. High-dose opioid anesthesia was introduced as a "stress-free" anesthetic method for cardiac surgery. However, several factors have diminished the popularity of high-dose opioid anesthesia, even in cardiac anesthesia. These include the lack of evidence substantiating any significant outcome benefit associated with the use of large doses of opioids,[207] [227] the added drug costs, and the trend toward "fast track" approaches to the cardiac patient that can be impeded by large doses of opioids, especially fentanyl.[226] [397] However, opioids, particularly when administered by continuous infusion, are still among the most effective anesthetics for patients undergoing cardiac or other extensive operations.
High-dose opioid anesthesia was first performed using morphine. However, morphine is no longer recommended, and fentanyl and sufentanil are recommended ( Fig. 11-28 ).[398] [399] Many different techniques have been used by clinicians and investigators to achieve anesthesia with fentanyl.[397] [400] [401] Rapid or slow bolus injections of fentanyl range from 5 to 75 µg/kg. These doses will establish sufficient plasma fentanyl concentrations (10–30 ng/mL) that are often sufficient to provide stable hemodynamics throughout the induction/intubation sequence. Continuous infusions of fentanyl for cardiac surgery range from 0.1 to 1.0 µg/kg/minute up to or continuing through CPB. High-dose fentanyl anesthesia has also proved effective and safe in premature infants for repair of patent ductus arteriosus (<50 µg/kg)[402] and for pediatric heart surgery (50–100 µg/kg).[403] A recent report indicated that fentanyl (25–50 µg/kg) combined with isoflurane (0.2%–0.4%) was sufficient to obtund hemodynamic and stress responses in the pre-CPB phase of open heart surgery in infants and young children.[404] On the other hand, high-dose fentanyl 75–100 µg/kg was shown to cause prolonged suppression of NK cell function.[405]
The induction of anesthesia with large doses of alfentanil has been applied to cardiac surgery.[406] Large doses (150 µg/kg) may be used with or without thiopental to induce anesthesia. Other investigators claim that anesthesia cannot be reliably induced with alfentanil alone, at least in young and healthy adults.[407] Continuous infusions of alfentanil (2–12 µg/kg/minute) have been employed to maintain moderate to very high plasma alfentanil concentrations (<3000 ng/mL) during cardiac surgery. Enthusiasm for high-dose alfentanil anesthesia techniques is limited by the amount (and cost) of drug required and by suggestions that alfentanil anesthesia for cardiac surgery may be inadequate[176] and may be associated with more cardiovascular adverse effects compared with fentanyl and sufentanil.[206] More modest doses of alfentanil have been successfully administered in combination with sedative-hypnotics such as propofol for cardiac anesthesia.[408]
Figure 11-28
Hemodynamic changes during cardiac surgery in patients
administered with morphine, fentanyl, or sufentanil. Total doses were 4.4 mg/kg,
95.4 µg/kg and 18.9 µg/kg for morphine, fentanyl and sufentanil, respectively.
Cardiovascular variables were analyzed before induction (C), and at the time of
maximal (MX) and minimal (MN) systolic arterial pressure change after induction (I),
insertion of oral airway (OA), insertion of Foley catheter (F), laryngoscopy + endotracheal
lidocaine spray (L&S), laryngoscopy + endotracheal intubation (L&T), leg
incision (LI), sternal incision (SI), sternal saw (SAW), and sternal spread (SP).
(From Benthuysen JL, Foltz BD, Smith NT, et al: Prebypass hemodynamic stability
of sufentanil-O2
, fentanyl-O2
, and morphine-O2
anesthesia
during cardiac surgery: A comparison of cardiovascular profiles. J Cardiothorac
Anesth 12:749–757, 1988.)
Advantages of high-dose sufentanil include more rapid induction of anesthesia, better blunting or elimination of hypertensive episodes, greater reduction in left ventricular stroke work, with higher cardiac outputs, and more stable hemodynamics intraoperatively and/or postoperatively.[184] [399] [409] Induction doses of sufentanil range from 2 to 20 µg/kg administered as a bolus or infused over 2 to 10 minutes. Total doses of sufentanil employed in high-dose techniques usually range from 15 to 30 µg/kg. However, no additional benefit could be demonstrated in terms of hemodynamic control or EEG signs by increasing the dose of sufentanil from 3 to 15 µg/kg for the induction of anesthesia in patients premedicated with lorazepam.[410] It has been thought that muscle rigidity during induction of anesthesia with high-dose opioid causes difficult ventilation with a mask. It was shown that difficult ventilation during induction of anesthesia with sufentanil 3 µg/kg was due to upper airway closure at the level of the glottis or above.[411]
The amount of sufentanil required can be markedly influenced by the supplements employed concomitantly. For patients undergoing coronary artery surgery, induction (0.4 ± 0.2 µg/kg) and total maintenance (2.4 ± 0.8 µg/kg) doses of sufentanil were used in combination with propofol (1.5 ± 1 mg/kg for induction and 32 ± 12 mg/kg total). Interestingly, sufentanil requirements tripled when midazolam was employed instead of propofol. [412] Etomidate, combined with an opioid, can provide excellent anesthetic conditions with minimal hemodynamic perturbations. Inducing anesthesia with sufentanil (0.5–1.0 µg/kg) and etomidate (0.1–0.2 mg/kg) frequently confers hemodynamic stability. Maintenance of anesthesia, utilizing an infusion of sufentanil (1.0–2.0 µg/kg/hour), in a balanced anesthetic technique, achieves the advantages of an opioid-based anesthetic and avoids prolonged opioid action into the postoperative period.
Remifentanil has been employed in cardiac anesthesia.[413] The pharmacokinetics of remifentanil were studied in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.[414] Because the volume of distribution increases by 86% with institution of CPB, and elimination clearance decreases by 6.37% for each degree below 37°C, the infusion rate of remifentanil should be changed to maintain constant plasma remifentanil level. It was shown that induction with remifentanil (2 µg/kg) together with propofol and maintenance with remifentanil at 0.25 or 0.5 µg/kg/min provided appropriate anesthesia for minimally invasive coronary artery bypass surgery with rapid awakening and tracheal extubation ( Fig. 11-29 ). [415]
In an attempt to decrease the costs of cardiac surgery, fast-track programs have been popular. Engoren and coworkers recently reported that the more expensive but shorter-acting opioids sufentanil and remifentanil produced equally rapid extubation, similar stays, and similar costs to fentanyl, indicating that any of these opioids can be recommended for fast-track cardiac surgery.[416]
Figure 11-29
Times to awakening (open circles)
and tracheal extubation (closed circles) in patients
who underwent minimally invasive direct coronary artery bypass surgery after an intravenous
anesthesia with remifentanil-propofol or alfentanil-propofol. (From Ahonen
J, Olkkola KT, Verkkala K, et al: A comparison of remifentanil and alfentanil for
use with propofol in patients undergoing minimally invasive coronary artery bypass
surgery. Anesth Analg 90:1269–1274, 2000.)
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