JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS
AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
A&A International Anesthesia Research Society
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow CME: Take the course for this article:
 Role of the Anesthesiologist in Fast-Track Surgery
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by White, P. F.
Right arrow Search for Related Content
PubMed
Right arrow Articles by White, P. F.
Related Collections
Right arrow Anesthesia Practice
Right arrow Ambulatory

Anesth Analg 2007;104:1380-1396
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000263034.96885.e1

AMBULATORY ANESTHESIA

The Role of the Anesthesiologist in Fast-Track Surgery: From Multimodal Analgesia to Perioperative Medical Care

Paul F. White, PhD, MD*, Henrik Kehlet, MD, PhD{dagger}, Joseph M. Neal, MD{ddagger}, Thomas Schricker, MD, PhD§, Daniel B. Carr, MD||¶, Franco Carli, MD, MPhil§, and the Fast-Track Surgery Study Group

From the *Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, Texas; {dagger}Section for Surgical Pathophysiology, The Juliane Marie Centre, Rigshospitalet, Copenhagen, Denmark; {ddagger}Department of Anesthesia, Virginia Mason Medical Centre, Seattle, Washington; §Department of Anesthesia, McGill University Health Centre, Montreal, Canada; ||Department of Anesthesia, Tufts-New England Medical Center, Boston, Massachusetts; and ¶Javelin Pharmaceuticals, Cambridge, Massachusetts.

Address correspondence and reprint requests to Paul F. White, PhD, MD, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, Texas. Address e-mail to paul.white{at}utsouthwestern.edu.


   Abstract
Top
 Abstract
Introduction
 PREOPERATIVE ISSUES
 FAST-TRACK ANESTHETIC TECHNIQUES
 POSTOPERATIVE ISSUES
 INTERACTIONS WITH SURGEONS AND...
 CONCLUSIONS
 REFERENCES
 
BACKGROUND: Improving perioperative efficiency and throughput has become increasingly important in the modern practice of anesthesiology. Fast-track surgery represents a multidisciplinary approach to improving perioperative efficiency by facilitating recovery after both minor (i.e., outpatient) and major (inpatient) surgery procedures. In this article we focus on the expanding role of the anesthesiologist in fast-track surgery.

METHODS: A multidisciplinary group of clinical investigators met at McGill University in the Fall of 2005 to discuss current anesthetic and surgical practices directed at improving the postoperative recovery process. A subgroup of the attendees at this conference was assigned the task of reviewing the peer-reviewed literature on this topic as it related to the role of the anesthesiologist as a perioperative physician.

RESULTS: Anesthesiologists as perioperative physicians play a key role in fast-track surgery through their choice of preoperative medication, anesthetics and techniques, use of prophylactic drugs to minimize side effects (e.g., pain, nausea and vomiting, dizziness), as well as the administration of adjunctive drugs to maintain major organ system function during and after surgery.

CONCLUSION: The decisions of the anesthesiologist as a key perioperative physician are of critical importance to the surgical care team in developing a successful fast-track surgery program.


   Introduction
Top
 Abstract
 Introduction
PREOPERATIVE ISSUES
 FAST-TRACK ANESTHETIC TECHNIQUES
 POSTOPERATIVE ISSUES
 INTERACTIONS WITH SURGEONS AND...
 CONCLUSIONS
 REFERENCES
 
The concept of fast-track surgery using multimodal perioperative rehabilitation programs (1) was introduced in the early 1990s to facilitate an early discharge from the hospital and more rapid resumption of normal activities of daily living after elective surgery. The increasing popularity of minimally invasive surgical techniques has also allowed patients to undergo increasingly complex surgical procedures on an ambulatory and/or short-stay basis (2). Therefore, fast-tracking implies implementation of a perioperative patient care paradigm that reduces the time to discharge home and resumption of activities of daily living after both major (inpatient) and minor (outpatient) surgical procedures.

The role of the anesthesiologist has evolved from that of a physician primarily concerned with providing optimal surgical conditions and minimizing pain immediately after the operation, to that of a perioperative physician responsible for ensuring that patients with coexisting medical conditions are optimally managed before, during, and after surgery (3,4). In addition to optimizing preoperative medication and providing the best possible intraoperative surgical conditions, the ability to provide for a rapid emergence from anesthesia and avoid postoperative side effects and early complications has assumed increasing importance for both outpatients and inpatients undergoing fast-track surgery. The evaluation of clinically meaningful outcomes (e.g., quality of recovery, resumption of normal activities of daily living) has increasingly become a focal point of anesthesia-related clinical research involving new drugs and techniques.

The Fast-Track Surgery Study Group is a multidisciplinary group of clinical investigators interested in critically evaluating the peer-reviewed literature related to surgical and anesthetic practices, as well as pre- and postoperative care directed at facilitating the recovery process after elective surgery. The primary aim of this article is to focus on specific aspects of perioperative care in which the anesthesiologist's contribution facilitates the recovery process. Ideally, the process begins in the preoperative period and extends into the postdischarge period. The anesthetic and analgesic techniques for facilitating the recovery process apply to all patients undergoing surgical procedures whether they are hospitalized or discharged home on the day of surgery. The complementary role of surgery and nursing care in the fast-tracking process are also discussed.


   PREOPERATIVE ISSUES
Top
 Abstract
 Introduction
 PREOPERATIVE ISSUES
FAST-TRACK ANESTHETIC TECHNIQUES
 POSTOPERATIVE ISSUES
 INTERACTIONS WITH SURGEONS AND...
 CONCLUSIONS
 REFERENCES
 
Premedication
Preanesthetic medication is given primarily to provide sedation, reduce anxiety, optimize intraoperative hemodynamic stability, and decrease postoperative side effects (5). Benzodiazepines remain the most commonly used premedications because even small doses of these compounds (e.g., midazolam 20 µg/kg IV) can improve the perioperative fast-tracking process by reducing anxiety and anxiety-related complications, as well as improving patient comfort and satisfaction (6). With respect to improving surgical outcome, both the β-blockers and {alpha}2-agonists are increasingly popular adjuvants to fast-track anesthetic techniques. As a result of their anesthetic and analgesic-sparing effects (7–11), these compounds can facilitate the early recovery process, improve perioperative hemodynamic stability, and reduce postoperative pain. Premedication with the {alpha}2-agonist clonidine or dexmedetomidine has been associated with a reduction in the use of opioid analgesics, postoperative nausea and vomiting (PONV), and intraoperative blood loss (10–12). IV clonidine combined with epidural clonidine improves analgesia and shortens the duration of paralytic ileus after colorectal procedures (13). The inhibitory effects of these {alpha}2-agonists on the sympathoadrenergic and hypothalamo-pituitary stress response (14) facilitate glycemic control in type-2 diabetic patients (15) and reduce myocardial ischemia after surgery (16).

β-blockers (e.g., atenolol) suppress surgery-induced increases in circulating catecholamines, and prevent untoward perioperative cardiovascular events in elderly patients undergoing noncardiac surgery (7). Evidence suggests that β-blockers are most effective in reducing cardiac events in surgical patients with preexisting coronary artery disease (17,18). Perioperative β-blockade improved hemodynamic stability during emergence from anesthesia and in the early postoperative period. The anesthetic and analgesic-sparing effects of β-blockers also lead to a faster emergence from anesthesia and reduce postoperative side effects (e.g., PONV). The anticatabolic properties of β-blockers may also facilitate the resumption of normal activities after major surgery procedures. In critically ill patients, β-blocker therapy combined with total parenteral nutrition can establish a positive protein balance (19).

Hydration Status
Elective surgery has traditionally been performed after an overnight fast to ensure an empty stomach and minimize the risk of aspiration during the perioperative period. However, many studies have demonstrated that avoiding fasting-induced dehydration (e.g., allowing oral intake of clear liquids up to 2–3 h before surgery and IV hydration before induction of anesthesia) is both safe and effective in reducing postoperative side effects (20–23). Liberal (versus restrictive) fluid administration during laparoscopic surgery also leads to improved patient outcomes (24,25). One study recommended that even obese patients without comorbid conditions should be allowed to drink clear liquids until 2 h before elective surgery procedures (21). Preoperative administration of glucose-containing fluids, prevents postoperative insulin resistance and attenuates the catabolic responses to surgery while replacing fluid deficits (26,27). However, the effects of glucose-containing solutions on clinical outcomes, including the length of hospital stay, incidence of PONV, muscle strength and subjective well-being remain controversial (28,29).

Perioperative hydration includes correction of preoperative dehydration due to fasting, bowel preparation, and underlying disease, replacement of blood loss, and administration of maintenance fluids (30,31). Four aspects of perioperative fluid resuscitation appear to be relevant for improving surgical outcome: 1) fluid volume, 2) fluid composition, 3) type of surgery, and 4) hemodynamic goals. With the exception of pulmonary and major abdominal surgery, it is common practice to administer relatively large amounts of crystalloids even for procedures with minimal blood loss. For example, high intraoperative fluid therapy was associated with reduced side effects (e.g., pulmonary dysfunction, dizziness, drowsiness, thirst, and nausea/vomiting) and a shorter hospital stay after laparoscopic cholecystectomy (22,25). Although aggressive crystalloid administration during colorectal surgery improved tissue oxygenation (32), it did not decrease the risk of surgical wound infections (33). On the other hand, two studies have suggested that excess fluid hydration can increase postoperative morbidity and the length of the hospital stay after major abdominal surgery (34,35). Furthermore, perioperative water and salt restriction reduced cardiopulmonary and tissue healing complications and prevented hyperchloremic metabolic acidosis after abdominal surgery (36,37).

Goal-directed fluid administration targeting specific values for cardiac index, oxygen delivery, and oxygen consumption using synthetic colloids and inotropic drugs may further improve outcome and recovery in patients undergoing pulmonary, major abdominal and orthopedic procedures (38,39). Therefore, strategies, which avoid both hypovolemia and excessive intravascular volume postoperatively, are important in facilitating the fast-track recovery process (31).

Glycemic Control
Impaired glucose homeostasis during surgery can result in hyperglycemia (27). Recent evidence suggests that even moderate increases in blood glucose are associated with adverse outcomes, particularly in patients with cardiovascular, infectious, and neurological diseases (40,41). Intraoperative hyperglycemia is an independent risk factor for postoperative complications, including death after cardiac surgery (42–44). Morbidity and mortality correlated with mean blood glucose levels in a concentration-dependent manner in diabetic patients undergoing cardiac surgery (42,43). Van den Berghe et al. (45) also demonstrated superior surgical outcomes with strict normoglycemia in postoperative critically ill patients. Not surprisingly, improved glycemic control using a continuous perioperative insulin infusion reduces morbidity and mortality in diabetic patients undergoing cardiac surgery (46,47). Maintenance of normoglycemia also attenuates the systemic inflammatory response to cardiopulmonary bypass (48). Therefore, "tight" glycemic control clearly improves patient outcome after cardiac surgery (46–48), and other critical illnesses (49). Use of glucocorticoid steroids as part of a fast-track anesthetic technique may lead to transient postoperative hyperglycemia in at-risk surgery populations (e.g., diabetics) (50).

Temperature Control
Perioperative hypothermia can have a wide range of detrimental effects, which may include increased rates of wound infection, morbid cardiac events, blood loss, and even prolong the hospital stay (51–54). Studies suggest that maintaining normothermia during surgery may provide significant benefits for surgical patients by reducing postoperative morbidity (55). Hypothermia can be reduced by using forced-air warming blankets, and warming irrigation and IV fluids. In addition, warmed and humidified insufflation gases may decrease postoperative pain and the need for opioid analgesics and antiemetic therapy after laparoscopic surgery (56).


   FAST-TRACK ANESTHETIC TECHNIQUES
Top
 Abstract
 Introduction
 PREOPERATIVE ISSUES
 FAST-TRACK ANESTHETIC TECHNIQUES
POSTOPERATIVE ISSUES
 INTERACTIONS WITH SURGEONS AND...
 CONCLUSIONS
 REFERENCES
 
Local Anesthesia
Infiltration of local anesthetics around a surgical incision should be a component of all "balanced" fast-track anesthetic techniques (57,58). Local infiltration anesthesia alone provides adequate analgesia for superficial procedures (e.g., inguinal herniorrhaphy, breast and anorectal surgery, shoulder and knee arthroscopy), and is probably vastly under-utilized (59–61). Patient comfort can be improved if IV sedation-analgesia is used to supplement local anesthetic infiltration, particularly when the local anesthesia is not completely effective (59,62). However, use of IV adjuvants can also increase side effects (e.g., ventilatory depression, PONV) (63,64). The benefits of local wound infiltration in patients undergoing more invasive surgical procedures have not been as extensively studied. Although there is little evidence that preemptive analgesia involving local anesthetic injections at the surgical wound reduces the risk for developing persistent postoperative pain syndromes (65), it does lessen both intra- and postoperative opioid requirements as well as opioid-related side effects (66).

Many studies have demonstrated improved analgesia, greater patient satisfaction with pain management, and reduced PONV and hospital stay with infusion of local anesthetic at the surgical incision site (67). For example, patients receiving a continuous infusion of bupivacaine at the median sternotomy incision site after cardiac surgery not only experienced improved postoperative pain management, but were also able to ambulate earlier, leading to a reduced length of hospital stay (68). Infiltration of local anesthetic at portal sites and the gallbladder bed improves postoperative analgesia after laparoscopic cholecystectomy (69). Compared with neuroaxial or general anesthetic techniques, local anesthetic infiltration techniques reduce the risk of postoperative urinary retention associated with anorectal surgery (70) and inguinal herniorrhaphy (62,71). When used as the primary anesthetic technique, local anesthesia facilitates postanesthesia care unit bypass, thereby reducing recovery costs (59,62,70,72).

In summary, routine use of local anesthetics at incision sites can facilitate fast-track recovery after outpatient, and even some inpatient, surgical procedures.

Regional Anesthesia
IV regional anesthesia, peripheral nerve blocks, and "mini-dose" neuraxial blocks are the most popular regional anesthetic techniques used for fast-track surgery. Use of IV regional anesthesia for ambulatory hand surgery was associated with faster discharge and lower costs, when compared with either general anesthesia or a peripheral nerve block (72). As supplements to general anesthesia, peripheral nerve blocks (versus local infiltration) improve postoperative analgesia and reduce opioid-related side effects, thereby facilitating the fast-track recovery process (73). For example, suprascapular block improves the recovery profile after arthroscopic shoulder surgery performed under general anesthesia (74), but not after "open" surgery with an interscalene block (75). As the primary analgesic technique, peripheral nerve blocks are associated with shorter discharge times, improved analgesia, and fewer side effects compared with general anesthesia for hand (73,76), shoulder (77), anorectal (70), hernia repair (62,78), and knee surgery (79).

Although it is widely assumed that regional anesthesia offers advantages over general anesthesia with respect to speed of recovery (80), a recent metaanalysis suggested that there were no significant differences in ambulatory surgery unit time (81). However, use of continuous perineural catheters to administer local anesthetics can improve pain control and expedite hospital discharge after painful upper (82) and lower extremity (83) surgical procedures. In addition, the local analgesia can be continued at home after discharge (84). These beneficial findings were confirmed in a recent multicenter trial which used patient-controlled perineural local analgesia as an alternative to IV patient-controlled analgesia (PCA) with morphine (85). A recent metaanalysis confirmed the advantages of a peripheral catheter technique over a parenteral opioid-based analgesic technique for extremity surgery (86).

When central neuroaxis block techniques are used as a part of a fast-track regimen, it is important to select the most appropriate local anesthetic and adjuvant combination to avoid prolonged anesthetic effects that negatively impact on readiness for discharge (62). For instance, prolonging subarachnoid-induced analgesia with fentanyl rather than epinephrine avoids the prolonged time to micturition (87), and reduces the time to discharge from the hospital (88). As compared with conventional intrathecal doses of local anesthetics, use of so-called minidose lidocaine (10–30 mg), bupivacaine (3.5–7 mg), or ropivacaine (5–10 mg) spinal anesthetic techniques when combined with a potent opioid analgesic (e.g., fentanyl 10–25 µg or sufentanil 5–10 µg) can result in faster recovery of sensory and motor function (89,90). When compared to a monitored anesthesia care (MAC) technique for ambulatory knee surgery, a minidose spinal technique involving lidocaine and fentanyl achieved comparable recovery times after knee arthroscopy (60). For outpatient laparoscopic gynecologic surgery, this technique has also been reported to offer significant advantages over both conventional spinal and general anesthetic techniques (90,91). However, postoperative side effects (e.g., pruritus, nausea) are increased due to the intrathecal opioid (60).

Epidural analgesia can be a valuable adjuvant to fast-track anesthesia techniques for major surgery (92). The benefits of epidural analgesia are most apparent when used as part of a multimodal analgesic regimen (93,94). Both continuous epidural infusion and epidural PCA provide better static and dynamic pain relief than IV opioid-based PCA delivery systems (95). In addition, epidural local analgesia, compared to IV-PCA, reduced postoperative pulmonary complications after thoracic or upper abdominal surgery (96), improved perioperative nutritional profiles and health-related quality of life scores, while better preserving exercise capacity after colon surgery (97–99). These factors can facilitate the achievement of postoperative milestones (e.g., earlier tracheal extubation and discharge from the intensive care unit, as well as shorter time to ambulation), but there is little evidence that epidural analgesia actually reduces mortality or hastens hospital discharge even after major surgery (95,96). Although epidural analgesia improved analgesia and reduced pulmonary complications after aortic surgery (100) and thoracoabdominal esophagectomy (101), it did not consistently reduce ileus or the length of the hospital stay in these surgical populations.

Thoracic epidural analgesia with a local anesthetic can reduce ileus and lead to a faster discharge after colonic surgery when combined with multimodal analgesic techniques (102–104). However, the advantages of epidural analgesia over simple IV-PCA are not appearent when using a fast-track postoperative care plan (104). Although epidural analgesia decreases rehabilitation time after total knee arthroplasty (105) and improved pain control, it failed to facilitate rehabilitation after hip fracture surgery (106). Given that similar analgesia can be achieved using a perineural catheter technique (e.g., continuous femoral or popliteal nerve blocks) as with epidural local analgesia without the attendant risk of epidural-related complications (e.g., hematoma formation, abscesses, hemodynamic instability), peripheral nerve blocks would appear to be preferable for lower extremity surgery.

The use of epidural analgesia for minimally invasive surgery (e.g., laparoscopic colectomy, nephrectomy, prostatectomy) is highly questionable. Epidural anesthesia and analgesia for laparoscopic colectomy only facilitated recovery of bowel function when a traditional, nonaccelerated perioperative care program was used (107). Future advances in fast-track surgery techniques and perioperative use of peripheral µ-opioid antagonists (108) will likely further lessen the future role of epidural analgesia (109). Although epidural analgesia per se minimally impacts fast-track surgery, as a component of multimodal management strategy it can provide superior analgesia and physiologic advantages that facilitate attainment of clinical pathway goals after major surgery (95,96). For example, intrathecal opioids as part of a multimodal analgesia technique are increasingly used as part of fast-track cardiac anesthesia techniques (110–112). Although there were no differences in the rates of mortality or myocardial infarction after coronary artery bypass grafting with central neuroaxial analgesia when using local anesthetics, there were associated improvements in time to tracheal extubation, decreased pulmonary complications and cardiac dysrhythmias, and reduced postoperative pain and opioid analgesic requirements (113). When the need for systemic opioids are reduced, cardiac surgery patients are able to be extubated earlier and experience a reduced length of stay in the intensive care unit (111), as well as a faster recovery of bowel and bladder function (68).

Monitored Anesthesia Care
Compared with general endotracheal and central neuroaxis anesthetic techniques for superficial (noncavitary) surgical procedures, MAC-based techniques involving the use of local anesthesia via infiltration or peripheral nerve block in combination with and IV sedative-analgesic drugs can facilitate a fast-track recovery (62,63,70). The simplest local anesthetic technique, which provides adequate analgesia, is recommended to minimize the risk of side effects and complications (114).

Use of a MAC technique for inguinal hernia repair, anorectal, and hand surgery was associated with a decreased incidence and severity of postoperative pain, reduced need for opioid-containing analgesics, less PONV, constipation, ileus, urinary retention, and other opioid-related side effects (62,70,72). MAC techniques commonly involve the use of local anesthetic infiltration and/or peripheral nerve blocks using a mixture of lidocaine (2%) and bupivacaine (0.5%) or ropivacaine (0.5%) in combination with small doses of midazolam (1–3 mg IV) and a variable-rate propofol infusion (25–100 µg · kg–1 · min–1) (115). Increasingly, dexmedetomidine (0.5–1 µg/kg) (116) and ketamine (75–150 µg/kg) (117) are being used as alternatives to opioid analgesics like fentanyl (0.5–1 µg/kg) (118) or remifentanil (0.25–0.5 µg/kg boluses or 0.025–0.05 µg · kg–1 · min–1 infusion) (119), as part of a MAC anesthetic technique to reduce the ventilatory depression produced when combining a potent opioid analgesic with midazolam and propofol (119). Respiratory depression due to over sedation and a lack of vigilance is the leading cause of serious patient injuries during MAC (64).

In summary, use of MAC techniques can facilitate a fast-track recovery after surgery, since patients routinely bypass the postanesthesia care unit, and can be discharged home earlier due to the low incidence of postoperative side effects. However, careful intraoperative vigilance to avoid respiratory complications is mandatory to insure patient safety.

General Anesthesia
Despite the obvious advantages of local, regional and MAC anesthetic techniques, many patients (and surgeons) still prefer general anesthesia because they remain unaware of events during the operation. Propofol, 1.5–2.5 mg/kg, is clearly the IV induction drug of choice for fast-track anesthesia (120). The less-soluble volatile anesthetics, desflurane (3%–6%) and sevoflurane (0.75%–1.5%), appear to offer advantages over propofol and isoflurane for maintenance of general anesthesia with respect to facilitating the early recovery process (121–124). Nitrous oxide (50%–70%) remains a popular adjuvant during the maintenance period because of its anesthetic and analgesic-sparing effects, low cost, and favorable pharmacokinetic profile (125). However, remifentanil infusion (0.05–0.20 µg · kg–1 · min–1) is an increasingly popular alternative to nitrous oxide as an adjuvant to the less-soluble volatile anesthetics (126,127).

The β-blocking drugs (e.g., esmolol, labetalol) can be used as an alternative to short-acting opioid analgesics for controlling the transient, acute autonomic responses during surgery (128–130). Whenever possible, a laryngeal mask airway should be used as an alternative to a tracheal tube (131). If tracheal intubation is required, short (e.g., succinylcholine, mivacurium) (132) or intermediate-acting (e.g., cisatracurium, vecuronium, rocuronium) neuromuscular blocking drugs should be used (133). A novel cyclodextrin compound, sugammadex (134), is capable of facilitating a faster reversal of steroid-based, nondepolarizing neuromuscular blockers than either a combination of edrophonium-atropine or neostigmine-glycopyrrolate without anticholinergic side effects (135). Use of this reversal drug may also lead to earlier tracheal extubation after surgery and reduce postoperative respiratory complications resulting from residual muscle paralysis (134).

Use of volatile anesthetics (versus propofol) for maintenance of anesthesia will increase PONV in the early postoperative period (136). For patients receiving volatile anesthetics, the most cost-effective antiemetic prophylaxis technique consists of a combination of low-dose droperidol (0.625–1.25 mg IV) and dexamethasone (4–8 mg IV) (137,138) or methylprednisolone (125 mg IV) (139). If the patient is at increased risk for developing PONV, a 5-HT3 antagonist should also be added as part of a multimodal antiemetic regimen (140). The neurokinin-1 antagonists may play an increasingly important role in the management of emetic symptoms in the future. Finally, use of non-opioid analgesics [e.g., nonsteroidal antiinflammatory drugs (NSAIDs), cycloxygenase-2 (COX-2) inhibitors, acetaminophen, {alpha}2-agonists, glucocorticoids, ketamine, and local anesthetics] as part of a multimodal analgesic regimen will minimize postoperative pain and opioid-related side effects (66,141).

In summary, use of short-acting anesthetic agents and prophylactic drugs, which minimize postoperative side effects, and avoiding surgical misadventures, will enhance the ability to fast-track patients after both ambulatory (142) and major inpatient surgery procedures (110–113). Not surprisingly, combining the use of short-acting anesthetic techniques with an educational program has been reported to significantly increase fast-tracking in ambulatory centers (143). Although a majority of both adults and children can be fast-tracked after ambulatory surgery under general anesthesia, minimizing patient discomfort and anxiety is critically important in establishing a successful fast-track surgery program after all types of elective surgery (129,142–144). Finally, improving the titration of both IV and inhaled anesthetics by using cerebral monitoring devices may also facilitate the fast-tracking process (145–148). However, in spontaneously breathing (nonparalyzed) patients, the value of cerebral monitoring in facilitating the recovery process is questionable (149).


   POSTOPERATIVE ISSUES
Top
 Abstract
 Introduction
 PREOPERATIVE ISSUES
 FAST-TRACK ANESTHETIC TECHNIQUES
 POSTOPERATIVE ISSUES
INTERACTIONS WITH SURGEONS AND...
 CONCLUSIONS
 REFERENCES
 
Pain Management
Observational studies have confirmed that poorly controlled pain and associated PONV can delay discharge after ambulatory surgery (150). Improving postoperative pain control accelerates normalization of quality of life and functionality that may otherwise persist for weeks after an elective operation (151–153). According to a recent systematic review by Liu and Wu (154) there is "insufficient evidence to conclude that analgesic techniques influence postoperative mortality or morbidity" due to the current low incidences of complications. However, excessive reliance upon opioids for perioperative analgesia contributes to acute opioid tolerance and hyperalgesia (155), as well as dose-related side effects (e.g., hypoventilation, sedation, nausea and vomiting, urinary retention, ileus) that delay hospital discharge and add to the cost of surgical care (66,156). Although opioid infusions are frequently used both IV and epidurally, they do not improve postoperative pain management due to the rapid development of tolerance (157), and increased risk of ventilatory depression. Even if acute pain control has little or no beneficial economic or physiological effects, efforts to improve pain management are being mandated by accrediting agencies, and excessive reliance on opioid analgesics will lead to increased morbidity and mortality (158).

Multimodal (or "balanced") analgesia involves the use of more than one modality of pain control to obtain additive (or even synergistic) beneficial analgesic effects while reducing opioid-related side effects (159). Early fast-track studies demonstrated that these multimodal analgesic techniques can improve recovery and patient outcome after ambulatory procedures (160,161). This approach is currently the standard practice in fast-track clinical care plans (1,162) because reliance on a single non-opioid analgesic modality such as NSAIDs may not suffice to control severe pain, and reliance exclusively on opioids produces many undesirable side effects (141). Use of partial opioid agonists (e.g., tramadol) is associated with increased side effects and patient dissatisfaction compared with that of both opioid and non-opioid analgesics (163).

The clinically relevant benefits of multimodal analgesia remain controversial (154). Unfortunately, many individual studies are under-powered, the reporting of adverse effects of analgesic drugs has been inconsistent, and meta-analyses (or systematic literature reviews) have often pooled data inappropriately from studies involving diverse types of operations which lacked common internal controls, and estimated aggregate effects often used insensitive measures such as number-needed-to-treat (164–166). Furthermore, the definition of "multimodal" is not uniform in the anesthesia and surgery literature. In some contexts, multimodal analgesia refers to systemic administration of analgesic drugs with different mechanisms of action (142), while in other it refers to concurrent application of analgesic pharmacotherapy and regional analgesia (167). Despite these weaknesses in the published literature, recent meta-analyses have confirmed the opioid dose-sparing effect of NSAIDs (including the COX-2 inhibitors) and decreases in the opioid-related side effects of PONV and sedation (166,168,169). Improvements in late outcome variables may be possible with short-term use of these drugs in the postoperative period (170). However, these positive findings do not necessarily extend to discernible benefits on opioid- induced pruritus, urinary retention, and respiratory depression (168,169), nor are these benefits evident with the reduced opioid-sparing effect of acetaminophen (171).

Studies suggest that an opioid-sparing effect can be achieved postoperatively using a pharmacologically diverse variety of non-opioid adjuvants (i.e., ketamine, clonidine, dexmedetomidine, adenosine, gabapentin, pregabalin, glucocorticoids, esmolol, neostigmine, magnesium) (66). The current evidence from the peer-reviewed literature in support of these non-opioid adjuvants is summarized in Table 1. The recent attention given to opioid-related side effects as impediments to achieving a high degree of patient satisfaction and early discharge home after surgery has increased interest in local and regional anesthetic techniques (63), and led to the development of longer-acting local anesthetics (e.g., suspensions, liposomes, microspheres) (214–217) and continuous delivery methods (e.g., peripheral nerve and wound infusion techniques) (67,82–84,86). Although continuous local anesthetic techniques have become increasingly popular due to the availably of disposable delivery systems, the encouraging results from these early pilot studies must be balanced against the cost of the equipment and the resources need to manage these systems outside the hospital (38,217).


View this table:
[in this window]
[in a new window]

  		Table 1. Clinical Evidence for Addition of Selected Second Drugs to an Opioid or a Nonsteroidal Antiinflammatory Drug (NSAID) Cyclooxygenase-2 (COX-2) Inhibitors and Other Non-Opioid Compounds as Part of a Multimodal Analgesic Technique

 

An evaluation of multimodal analgesic therapy by Curatolo and Sveticic (172) in 2002 yielded 55 clinical trials and 47 randomized controlled trials relevant to the treatment of acute postoperative pain. These investigators concluded that adding a NSAID (or ketamine) to morphine was advantageous, and that the combination of acetaminophen and a NSAID is superior to either drug alone. Unfortunately, most multimodal analgesia studies have focused on the combination of an opioid with a single non-opioid drug. Ideally, multiple non-opioids (e.g., NSAIDs, acetaminophen, COX-2 inhibitors and gabapentin) could be combined to achieve more optimal pain relief and, perhaps ultimately, an opioid-free environment (66,141). Therefore, multimodal analgesia represents a key element for successful fast-track surgery by minimizing postoperative pain, opioid-related organ dysfunction and facilitating the recovery process from anesthesia. Newer fast-tracking criteria recognize the importance of controlling pain and opioid-related side effects (e.g., PONV) (218).

Nausea and Vomiting
Despite the introduction of many new antiemetic therapies, the incidence of PONV remains high, occurring in up to 30% of all surgical cases (including both cardiac and neurosurgery) due to patient, anesthesia and surgery-related factors (219). The major risk factors for PONV include female gender, nonsmoker status, history of PONV or motion sickness, intraoperative use of volatile anesthetics and high-dose opioid techniques, as well as postoperative opioid analgesic use (220). In adults, a multidrug antiemetic prophylaxis strategy is recommended for patients who present with two or more risk factors (221). In addition to the administration of antiemetic drugs, multimodal strategies to reduce the risk of PONV include use of propofol and local anesthetic-based analgesic techniques, adequate hydration, as well as minimizing perioperative opioid use (222). Use of cardiovascular drugs (e.g., β-blockers, {alpha}2-agonists) to control transient acute autonomic responses to noxious surgical stimuli and non-opioid analgesics to reduce postoperative pain will minimize emetic symptoms (66,129,130). Nonpharmacological techniques (e.g., acupuncture, acupressure, and transcutaneous electrical nerve stimulation) can be useful adjuvants to standard antiemetic drugs when used after surgery (223–225). Therefore, replacing intravascular fluid deficits, minimizing use of volatile anesthetics and nitrous oxide, opioid analgesics and reversal drugs, and using propofol, multimodal antiemetic prophylaxis and non-opioid analgesic techniques are all important factors in preventing PONV (141). In the future, practitioners should also consider incorporating alternative medical therapies into their treatment plans (226).

Ileus and Constipation
Postoperative ileus can cause discomfort and delay oral food intake, thereby prolonging convalescence and the length of the hospital stay (227). The key elements in a multimodal fast-track strategy for preventing postoperative ileus include use of minimally invasive surgical techniques, use of a peripherally acting µ-opioid receptor antagonist, avoidance of a nasogastric (NG) tube, early oral feeding and ambulation, and opioid-sparing analgesic regimens (228). One of the most important factors in accelerating the return of bowel function after major abdominal surgery is the use of continuous thoracic epidural local analgesia (227,229). The positive effect of epidural analgesia on bowel function appears to be related to segmental visceral afferent and efferent blockade. Therefore, thoracic epidural infusion of a local anesthetic solution should reduce the duration of ileus after major abdominal surgery (99).

Multimodal rehabilitation paradigms, which combine epidural analgesia with early oral feeding and mobilization, have been found to decrease the duration of ileus (227). In addition, there is evidence that reduced perioperative sodium administration and avoidance of fluid excess is associated with earlier return of bowel function after abdominal surgery (230), and a decrease in the length of the hospital stay (231). The results of recent clinical trials indicate that use of a peripheral µ-opioid receptor antagonist (i.e., alvimopan, methylnaltrexone) can facilitate the recovery of postoperative bowel activity and may reduce the time to hospital discharge after major surgical procedures (108,232,233). Importantly, minimizing the use of opioid-containing oral analgesics after discharge reduces both constipation and PONV (234).

Nutritional Supplementation
The objective of nutritional management of surgical patients is to accelerate wound healing and increase resistance to infection while preventing loss of functional and structural proteins (97). Administration of hypercaloric amounts of glucose in combination with amino acids is the only nutritional modality that has been shown to produce a positive effect on protein balance (i.e., anabolism). Clinical studies support the concept that enteral nutrition is preferable to parenteral nutrition, and that early (versus late) oral feeding is advantageous with respect to improved surgical outcomes (235–237). Parenteral nutrition is a useful strategy only in surgical patients who are unable to resume oral feeding. Hyperalimentation requiring central venous cannulation should be avoided because it causes hyperglycemia, which can increase postoperative morbidity (238). The choice of perioperative analgesia (e.g., epidural local analgesia versus IV PCA with opioid analgesics) can also affect the perioperative feeding strategy (98). Epidural analgesia facilitates glucose use and improves insulin sensitivity, thereby diminishing the amount of energy required to attenuate the catabolic losses after major intracavitary surgery (97,239,240). In addition, epidural local analgesia facilitates recovery of ileus and allows earlier resumption of oral nutrition.


   INTERACTIONS WITH SURGEONS AND NURSES IN FACIITATING THE RECOVERY PROCESS
Top
 Abstract
 Introduction
 PREOPERATIVE ISSUES
 FAST-TRACK ANESTHETIC TECHNIQUES
 POSTOPERATIVE ISSUES
 INTERACTIONS WITH SURGEONS AND...
CONCLUSIONS
 REFERENCES
 
Since the principles of fast-track surgery by definition include a multidisciplinary approach, the "total care" principle involves anesthesiologists as members of the perioperative care team with surgical, nursing, and rehabilitation personnel. The benefits of the anesthesiologist's fast-track anesthetic techniques can only be fully realized when they are incorporated into a comprehensive perioperative patient care plan (162). Compared to traditional postoperative care after colon surgery, patients cared for by surgeons experienced in using fast-tracking protocols had shorter hospital stays (4.5 d vs 7–10 d) (229,241). However, no differences were found in the postoperative activity levels, suggesting that reductions in the length of stay were related to factors other than changes in the patient's level of physical activity after surgery (242).

Technical and Procedural Aspects of Surgical Care
There have been recent advances in minimally invasive surgery in almost all surgical specialties. As a result of this paradigm shift, there have been beneficial effects on perioperative organ function including improvements in nociceptive control (i.e., reduced pain) and pulmonary function (i.e., less atelectasis), decreased cardiac demands, and reduced endocrine-metabolic responses, muscle catabolism, and inflammatory responses. Laparoscopic (versus open) colectomy and nephrectomy was associated with longer operating times, but significantly reduced the length of the hospital stay and the time to resume normal activities of daily living (243,244). In a metaanalysis of published studies involving laparoscopic (versus open) procedures, Abraham et al. (244) reported that resections for colorectal cancer required 33% more time in the operating room (OR). However, the time to pass flatus was reduced by 34%, and the time to tolerate dietary intake was decreased by 24%. Postoperative pain scores and the need for opioid analgesics were reduced by 34%–63% during the first 3 days after surgery. The greatest benefits of minimally invasive surgery are for operations where the alternative is a large incision (e.g., esophageal reflux surgery, bariatric surgery, splenectomy, thoracic, vascular procedures, arthroscopy, adrenalectomy, and nephrectomy). However, the differences are less pronounced with other types of surgery (e.g., colonic resection, appendectomy, cholecystectomy, inguinal herniorrhaphy).

Importantly, the maximal benefits of minimally invasive surgery (e.g., laparoscopic techniques) can only be achieved when perioperative care principles are adjusted to the principles of fast-track surgery in order to take advantage of the reduced disturbance in perioperative pathophysiology (245). The differences between minimal invasive surgery per se and "open" surgery combined with a fast-track recovery strategy become small, or may even favor open procedures in some situations (e.g., colonic resection). Therefore, there is still a need for prospective, randomized, patient and observer-blinded studies to define the role of minimally invasive surgery for many common surgical procedures.

Only two blinded studies with planned early recovery programs have been published, and these studies demonstrated no clinically important differences between open and laparoscopic colonic resection (246) or appendectomy (247). A similar criticism can be made about many of the published series comparing recovery after a so-called fast-track multimodal rehabilitation program to "conventional recovery care." Most of these series are nonrandomized and involve the use of historical control groups. Many of these comparative studies have emphasized the ability to achieve a shorter hospital stay, reduced postoperative fatigue, and earlier resumption of normal activities without an increase need for additional support after discharge with fast-track multimodal rehabilitation programs (248,249). However, concerns have been raised regarding the possibility of a higher readmission rate (250), and the need for more effective communication and education regarding postdischarge care (251).

In implementing fast-track surgical programs, several surgical aspects of care (e.g., type of incision, use of drains, NG tubes, urinary catheters, bowel preparation) must be revised based on current evidence (1,162). For example, several randomized studies have demonstrated less pain and pulmonary dysfunction with transverse (versus vertical) incisions (252,253). A possible explanation for this improved outcome relates to the larger number of dermatomal levels being disrupted by vertical incisions. In order to facilitate early functional recovery, traditional care principles that hinder early mobilization and feeding must be changed. For elective mid-to-lower abdominal procedures, the routine use of NG tubes should be avoided (254), since their use can prolong paralytic ileus, hinder oral intake, cause oropharyngeal discomfort, and predispose the patient to pulmonary morbidity (e.g., aspiration pneumonitis). Similarly, prolonged routine use of surgical drains should be avoided because randomized clinical trials have demonstrated that they are not necessary and can have detrimental effects on recovery after hepatic, colonic, and rectal resections with primary anastomoses, as well as appendectomy (255). The traditional bowel preparation (e.g., polyethylene glyol-electrolyte solution) prior to abdominal procedures may actually increase the risk of infectious morbidity (256,257). The same situation may also apply to the use of urinary catheters (1). In addition, the surgical care principles must be adjusted based on recent evidence regarding optimal fluid management (31) and adequate early oral nutrition (258).

Finally, surgical patients undergoing major surgery who are unfit and who have comorbid illnesses experience more postoperative complications and a longer convalescence period (99). The process of enabling surgical patients to withstand the adverse effects of surgery-induced inactivity by increasing their exercise capacity through preoperative conditioning (i.e., physical training) is termed "prehabilitation" (259). This consists of a program of aerobic and resistance exercises over a period of 3–4 wk before elective surgery. Preliminary studies suggest that a prehabilitation program can increase preoperative exercise capacity by 15%–20%, even in lower risk patients undergoing cardiac surgery (260). A recent study by Hulzebos et al. (261) found that preoperative inspiratory muscle training reduced the incidence of postoperative pulmonary complications and the duration of hospital stay after coronary artery bypass graft surgery. A perioperative exercise program was also found to be effective in improving early recovery of physical function after total hip arthroplasty in the elderly (262). Simple walking tests (using pedometers, accelerometers, and treadmills to monitor daily activity) may be useful predictors of postoperative recovery (263).

Changing the Postsurgical Nursing Culture
A common experience at centers implementing fast-track surgery has been the challenge of changing long-standing surgical nursing care principles (264,265), and this is a major component of the total care package (266). An intensified nurse-based preoperative patient education program is a crucial adjunct to improved fast-track anesthetic surgical care (143). These programs need to focus on what is expected from the patient as an active participant in the recovery and rehabilitation process (267). The provision of daily nurse care (i.e., clinical pathway) charts remains an important element in the fast-track recovery process. It is essential to secure daily tasks, and to establish programs to facilitate education of new personal as every aspect of care must be carefully explained. Therefore, multidisciplinary meetings before and after implementing fast-track surgery are crucial to the overall success of the program. These meetings should include a presentation of results and patient follow-up in order to facilitate an understanding of the goals and results of fast-track surgery compared with traditional recovery care.


   CONCLUSIONS
Top
 Abstract
 Introduction
 PREOPERATIVE ISSUES
 FAST-TRACK ANESTHETIC TECHNIQUES
 POSTOPERATIVE ISSUES
 INTERACTIONS WITH SURGEONS AND...
 CONCLUSIONS
REFERENCES
 
As perioperative physicians, anesthesiologists play an important role in the implementation of fast-track surgery programs (Table 2). Understanding the importance of coexisting diseases and taking appropriate steps to minimize postoperative complications through appropriate use of preoperative medications, selecting the optimal anesthetic and analgesic techniques, and maintaining normal organ system function will lead to improved patient care at a reduced cost (268). As more information becomes available, it should be possible to make recommendations for each of these steps on a procedure-specific basis, as has been achieved for postoperative pain management (www.postoppain.org).


View this table:
[in this window]
[in a new window]

  		Table 2. Key Elements of the Perioperative Anesthetic Management for Facilitating a Fast-Track Recovery After Elective Surgery

 

Future advances in fast-track surgery will require interdisciplinary collaborations involving anesthetic, surgery and nursing care (Table 3) (269). However, anesthesiologists are the ones who make the important decisions regarding premedication, fluid management, anesthetic and adjuvant drugs, treatment of side effects, and pain management in the early postoperative period. Interventions to modify surgical stress responses are also performed by anesthesiologists and include perioperative use of β-blockers, glucocorticoid steroids, administration of fluids, as well as control of stress-induced hyperglycemia by administering insulin (30,66,269). The effective control of stress responses will likely prove to be advantageous with respect to improving patient outcome. Furthermore, an expansion of the anesthesiologists' interventions beyond the operating and recovery rooms may also be necessary. Preliminary data suggest that positive outcome effects may be achieved when anesthesiologists participate in ward rounds in the later postoperative period (270), or if an outreach service is established for early recognition of organ dysfunction (271).


View this table:
[in this window]
[in a new window]

  		Table 3. Future Strategies for Anesthesiologist to Advance Fast-Track Surgery

 

Perioperative anesthetic care should, therefore, be considered as a multidisciplinary strategy to improve the management and outcome of patients undergoing surgery, rather than a subspeciality limited to one medical profession (272). As a member of the multidisciplinary team, the decisions of the anesthesiologist have a direct impact on the ability to achieve a fast-track recovery after surgery (4,162). It has recently been reported that an anesthesiologist-led management team improved OR efficiency (resulting in a 48% reduction in gap time between cases in the same OR) when defined scheduling policies were supported by surgeons, nurses, and hospital administrators (273). In addition, the implementation of a multidisciplinary approach to minimizing common postoperative side effects can lead to a reduced recovery room and hospital stay, as well as better pain control and patient satisfaction after surgery (274,275). However, more prospectively randomized, controlled studies involving multidisciplinary approaches to facilitating a fast-track recovery are needed.

The role of the anesthesiologists would ideally expand beyond the time of hospitalization since effective pain control after discharge is critically important for achieving successful convalescence (4,13,66,141). Anesthesiologists may contribute by encouraging the optimal use of multimodal analgesia, as well as in implementing novel techniques, which can improve pain control and minimize side effects (e.g., PONV, ileus) after the patient has been discharged home (2,84,226,233). The time is right for anesthesiologists to take a more active role as perioperative physicians in implementing fast-track surgery programs.


   Footnotes
 
Accepted for publication February 28, 2007.

The meeting which generated the interest in this program was supported by an unrestricted educational grant from Ethicon Endo-Surgery, Inc (Cincinnati, OH).

Fast-Track Surgery Study Group consisted of the following individuals: Franco Carli, Wesley Bourne Professor, McGill University Health Center, Montreal, Canada; Daniel B. Carr, Saltonstall Professor of Pain Research, Tufts-New England Medical Center, Boston, MA; Frances Chung, Professor, University of Toronto, Canada; Gerald M. Fried, Adair Chair of Surgical Education, Steinberg-Bernstein Chair of Minimally Invasive Surgery and Surgical Innovation, McGill University Health Center, Montreal, Canada; Henrik Kehlet, Professor, The Juliane Marie Centre, Copenhagen, Denmark; Nancy E. Mayo, James McGill Professor, McGill University Health Center, Montreal, Canada; Joseph M. Neal, Clinical Professor, Virginia Mason Medical Centre, Seattle, WA; Thomas Schricker, Associate Professor, McGill University Health Centre, Montreal, Canada; Anthony J. Senagore, Professor and Chairman, Medical University of Ohio; Daniel I. Sessler, Vice Dean and Associate VP for Health Affairs, Interim Chair and L&S Weakley Professor of Anesthesiology, University of Louisville, KY, Paul F. White, Professor and Holder of the Margaret Milam McDermott Distinguished Chair in Anesthesiology, University of Texas Southwestern Medical Center at Dallas, TX; Douglas Wilmore, Professor, Harvard Medical School, Boston, MA; Gerald S. Zavorsky, Assistant Professor, McGill University Health Centre, Montreal, Canada.


   REFERENCES
Top
 Abstract
 Introduction
 PREOPERATIVE ISSUES
 FAST-TRACK ANESTHETIC TECHNIQUES
 POSTOPERATIVE ISSUES
 INTERACTIONS WITH SURGEONS AND...
 CONCLUSIONS
 REFERENCES
 

  1. Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome. Am J Surg 2002;183:630–41.[ISI][Medline]
  2. White PF. Ambulatory anesthesia advances into the new millennium. Anesth Analg 2000;90:1234–5.[Free Full Text]
  3. Halaszynski TM, Juda R, Silverman DG. Optimizing postoperative outcomes with efficient preoperative assessment and management. Crit Care Med 2004;32:S76–86.[ISI][Medline]
  4. Hensel M, Schwenk W, Bloch A, et al. The role of anesthesiology in fast track concepts in colonic surgery. Anaesthesist 2006;55:80–92.[ISI][Medline]
  5. White PF. Pharmacologic and clinical aspects of preoperative medication. Anesth Analg 1986;65:963–74.[Free Full Text]
  6. van Vlymen JM, Sa Rego MM, White PF. Benzodiazepine premedication: can it improve outcome in patients undergoing breast biopsy procedures. Anesthesiology 1999;90:740–7.[ISI][Medline]
  7. Zaugg M, Tagliente T, Lucchinetti E, et al. Beneficial effects from β-adrenergic blockade in elderly patients undergoing noncardiac surgery. Anesthesiology 1999;91:1674–86.[ISI][Medline]
  8. Johansen JW, Flaishon R, Sebel PS. Esmolol reduces anesthetic requirement for skin incision during propofol/nitrous oxide/morphine anesthesia. Anesthesiology 1997;86:364–71.[ISI][Medline]
  9. Chia YY, Chan MH, Ko NH, Liu K. Role of β-blockade in anaesthesia and postoperative pain management after hysterectomy. Br J Anaesth 2004;93:799–805.[Abstract/Free Full Text]
  10. Segal IS, Jarvis DJ, Duncan SR, et al. Clinical efficacy of oral-transdermal clonidine combinations during the perioperative period. Anesthesiology 1991;74:220–5.[ISI][Medline]
  11. Arain SR, Ruehlow RM, Uhrich TD, Ebert TJ. The efficacy of dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery. Anesth Analg 2004;98:153–8.[Abstract/Free Full Text]
  12. Okuyama K, Inomata S, Toyooka H. The effects of prostaglandin E1 or oral clonidine premedication on blood loss during paranasal sinus surgery. Can J Anaesth 2005;52:546–7.[Free Full Text]
  13. Wu CT, Jao SW, Borel CO, et al. The effect of epidural clonidine on perioperative cytokine response, postoperative pain, and bowel function in patients undergoing colorectal surgery. Anesth Analg 2004;99:502–9.[Abstract/Free Full Text]
  14. Mertes N, Goetters C, Kuhlmann M, Zander JF. Postoperative {alpha}-2 adrenergic stimulation attenuates protein catabolism. Anesth Analg 1996;82:258–63.[Abstract]
  15. Belhoula M, Ciebiera JP, De La Chapelle A, et al. Clonidine premedication improves metabolic control in type 2 diabetic patients during ophthalmic surgery. Br J Anaesth 2003;90: 434–9.[Abstract/Free Full Text]
  16. Wallace AW, Galindez D, Salahieh A, et al. Effect of clonidine on cardiovascular morbidity after noncardiac surgery. Anesthesiology 2004;101:284–293.[ISI][Medline]
  17. Lindenauer PK, Pekow P, Wang K, et al. Perioperative β-blocker therapy and mortality after major noncardiac surgery. N Engl J Med 2005;353:349–61.[Abstract/Free Full Text]
  18. Devereaux P, Beattie W, Choi P, et al. How strong is the evidence for the use of perioperative β-blockers in patients undergoing noncardiac surgery? A systematic review and metaanalysis. BMJ 2005;331:313–21.[Abstract/Free Full Text]
  19. Herndon DN, Hart DW, Wolf SE, et al. Reversal of catabolism by β-blockade after severe burns. N Engl J Med 2001;345: 1223–9.[Abstract/Free Full Text]
  20. Maltby JR, Sutherland AD, Sale JP, Shaffer EA. Preoperative oral fluids is a five-hour fast justified prior to elective surgery. Anesth Analg 1986;11:1112–16.
  21. Maltby JR, Pytka S, Watson NC, et al. Drinking 300 mL of clear fluid two hours before surgery has no effect on gastric fluid volume and pH in fasting and non-fasting obese patients. Can J Anaesth 2004;51:111–15.[Abstract/Free Full Text]
  22. Yogendran S, Asokumar B, Cheng D, Chung F. A prospective, randomized double-blind study of the effect of intravenous fluid therapy on adverse outcomes after outpatient surgery. Anesth Analg 1995;80:682–6.[Abstract]
  23. Maharaj CH, Kallam SR, Malik A, et al. Preoperative intravenous fluid therapy decreases postoperative nausea and pain in high risk patients. Anesth Analg 2005;100:675–82.[Abstract/Free Full Text]
  24. Magner JJ, McCaul C, Carton E, et al. Effect of intraoperative intravenous crystalloid infusion on postoperative nausea and vomiting after gynaecological laparoscopy: comparison of 30 and 10 ml · kg–1. Br J Anaesth 2004;93:381–5.[Abstract/Free Full Text]
  25. Holte K, Klarskov B, Christensen DS, et al. Liberal versus restrictive fluid administration to improve recovery after laparoscopic cholecystectomy: a randomized, double-blind study. Ann Surg. 2004;240:892–9.[ISI][Medline]
  26. Ljungqvist O, Nygren J, Thorell A. Insulin resistance and elective surgery. Surgery 2000;128:757–60.[ISI][Medline]
  27. Hausel J, Nygren J, Thorell A, et al. Randomized clinical trial of the effects of oral preoperative carbohydrates on postoperative nausea and vomiting after laparoscopic cholecystectomy. Br J Surg 2005;92:415–21.[ISI][Medline]
  28. Bisgaard T, Kristiansen VB, Hjortsoe NC, et al. Randomized clinical trial comparing an oral carbohydrate beverage with placebo before laparoscopic cholecystectomy. Br J Surg 2004;91:151–8.[ISI][Medline]
  29. Noblett SE, Watson DS, Huong W, et al. Pre-operative oral carbohydrate loading in colorectal surgery: a randomized controlled trial. Colorectal Dis 2006;8:563–69.[ISI][Medline]
  30. Grocott MP, Mythen MG, Gan TJ. Perioperative fluid management and clinical outcomes in adults. Anesth Analg 2005;100: 1093–106.[Abstract/Free Full Text]
  31. Holte K, Kehlet H. Fluid therapy and surgical outcomes in elective surgery: a need for reassessment in fast-track surgery. J Am Coll Surg 2006;202:971–89.[ISI][Medline]
  32. Arkilic CF, Taguchi A, Charma N. Supplemental perioperative fluid administration increases tissue oxygen pressure. Surgery 2003;133:49–55.[ISI][Medline]
  33. Kabon B, Akca O, Taguchi A, et al. Supplemental intravenous crystalloid administration does not reduce the risk of surgical wound infection. Anesth Analg 2005;101:1546–1553.[Abstract/Free Full Text]
  34. Brandstrup B, Tonnesen H, Beier-Holgersen R, et al. The Danish Study Group on Perioperative Fluid Therapy. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens. A randomized assessor-blinded multicenter trial. Ann Surg 2003;238: 640–50.
  35. Nisanevich V, Felsenstein I, Almogy G, et al. Effect of intraoperative fluid management on outcome after intra-abdominal surgery. Anesthesiology 2005;103:25–32.[ISI][Medline]
  36. Scheingraber S, Rehm M, Sehmisch C, Finsterer U. Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology 1999;90:1265–70.[ISI][Medline]
  37. Waters JH, Gottlieb A, Schoenwald P, et al. Normal saline versus lactated Ringer's solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm: an outcome study. Anesth Analg 2001;93:817–822.[Abstract/Free Full Text]
  38. Gan TJ, Soppitt A, Maroof M, et al. Goal directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology 2002;97:820–6.[ISI][Medline]
  39. Venn R, Steele R, Richardson P, et al. Randomized controlled trial to investigate influence of the fluid challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures. Br J Anaesth 2002;88:65–71.[Abstract/Free Full Text]
  40. McAlister FA, Majumdar SR, Blitz S, et al. The relation between hyperglycemia and outcomes in 2471 patients admitted to the hospital with community-acquired pneumonia. Diabetes Care 2005;28:810–15.[Abstract/Free Full Text]
  41. Gandhi GY, Nuttall GA, Abel MD, et al. Intraoperative hyperglycemia and perioperative outcomes in cardiac surgery patients. Mayo Clin Proc 2005;80:862–6.[ISI][Medline]
  42. Anderson RE, Klerdal K, Ivert T, et al. Are even impaired fasting glucose levels preoperatively associated with increased mortality after CABG surgery. Eur Heart J 2005;26:1513–18.[Abstract/Free Full Text]
  43. Quattara A, Lecomte P, LeManach Y, et al. Poor intraoperative blood glucose control is associated with a worsened hospital outcome after cardiac surgery in diabetic patients. Anesthesiology 2005;103:687–94.[ISI][Medline]
  44. Rady MY, Ryan T, Starr NJ. Perioperative determinants of morbidity and mortality in elderly patients undergoing cardiac surgery. Crit Care Med 1998;26:225–35.[ISI][Medline]
  45. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001;345:1359–67.[Abstract/Free Full Text]
  46. Furnary A, Gao G, Grunkeimer GL, et al. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 2003;125:1007–21.[Abstract/Free Full Text]
  47. Furnary AP, Zerr K, Grunkemeier GL, Starr A. Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg 1999;67:352–62.[Abstract/Free Full Text]
  48. Visser L, Zuurbier CJ, Hoek FJ, et al. Glucose, insulin and potassium applied as perioperative hyperinsulinaemic normoglycaemic clamp: effects on inflammatory response during coronary artery surgery. Br J Anaesth 2005;95:448–57.[Abstract/Free Full Text]
  49. Krinsley JS. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc 2004;79:992–1000.[ISI][Medline]
  50. London MJ, Grunwald GK, Shroyer AL, Grover FL. Association of fast-track cardiac management and low-dose to moderate-dose glucocorticoid administration with perioperative hyperglycemia. J Cardiothorac Vasc Anesth 2000;14: 631–8.[ISI][Medline]
  51. Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the