Society of Cardiovascular Anesthesiologists

PRO: Short Acting Fast Emergence Agents are Necessary to Ensure the Success of a "Fast-Track" Extubation Program.

Martin J. London, M.D.

University of Colorado -

Health Sciences Center

Denver VA Medical Center

Denver, Colorado

Anesthesia for cardiac surgery is a continually moving target. We manage a "changing" patient population (older, more comorbid disease, higher risk anatomy, poor ventricular function, etc.). "Routine" cardiac surgical practice is constantly evolving and more complex (near universal use of IMA and other types of arterial grafts, etc.). "Innovative" practices, most notably "minimally invasive" approaches, which can be "maximally stressful", have "changed the rhythm" of routine practice in the heart room. Efforts at cost reduction and accelerated recovery, popularized under the umbrella term "Fast Tracking", are "the new reality". On top of all this, most of us have come to accept (and preach) that there is "no such thing as a cardiac anesthetic"! [1]

Our pharmacologic armamentarium has evolved to include multiple choices for each phase of the perioperative period administered either in "series or parallel". Desflurane, sevoflurane, isoflurane or maybe even enflurane or halothane? Rocuronium, vecuronium, doxacurium, pipecuronium, cisatracurium, or pancuronium or maybe even d-tubocurare? Remifentanil, sufentanil, alfentanil, fentanyl, or maybe even morphine or meperidine? Propofol, thiopental, midazolam, diazepam, etomidate, or ketamine? Intraop or early postop? A myriad of "personal" factors color one's preference for any of these agents (i.e. time from residency training, intravenous vs. inhalational preference, comfort with infusion devices, etc.). Equally important is one's practice setting which usually equates to the speed and skill of the surgeons. Those of us working in teaching settings or with slow private surgeons in "less efficient systems" have distinctly different "requirements" than those in faster, more efficient ones. Varying ICU recovery "models" will also impact on the potential role of anesthetics to reduce postop costs. [2]

Although multiple physiologic and "hospital-level" variables influence the recovery and outcome of a particular patient, the "mission" of an anesthetist should be to maximize the predictability of a "goal-directed" anesthetic tailored to a particular setting. [3] This includes the basic tenets of anesthesia (i.e. amnesia, analgesia and hemodynamic stability). However, with the near universal acceptance of Fast Tracking, facilitating early extubation (usually in the 2 - 6 hour time frame) in the most predictable manner for the highest percentage of patients with the least amount of residual drug effect is a paramount goal.

Short-acting, fast emergence anesthetics (the inflammatory, but nonetheless intriguing acronym, SAFE, coined for ambulatory surgery is wonderful for debate) are clearly more expensive than their older, generic, usually longer-acting and often less potent predecessors. Admittedly, cardiac anesthesia differs from ambulatory surgery in which there is more of a "continuous" relation between drug effect and recovery (i.e. extubate and mobilize as early as possible) in contrast to the "time delay" of an "extubation window" of several hours in which patient stability has been ensured. Given many factors that diminish the predictability of pharmacodynamic and kinetic response to anesthesia (i.e. older age, greater degrees of hemodilution, hypothermia, inflammatory response that may alter drug binding, metabolism, and elimination), it makes "physiologic sense" to use agents with a "cleaner profile". [4] SAFE anesthetics, by virtue of very low or nearly absent degrees of pharmacologic accumulation are uniquely suited for "less efficient" systems with lengthy surgery, since they may facilitate early extubation regardless of length of surgery (assuming other factors remain relatively constant). [5]

At our institution, we have had particular success in a wide variety of patients undergoing primary or redo revascularization using intraoperative infusions of sufentanil, propofol, and rocuronium supplemented by desflurane, sevoflurane or isoflurane. Our recent analysis suggesting that intraoperative "process of care" variables (including those related to anesthetic management) provide significant additive ability to predict timing of extubation independent of preoperative risk factors, supports this approach. [6] Our patients usually require little if any sedation prior to extubation due to the gradual and predictable reduction in anesthetic effects of these infusions. Alternative approaches use infusions (particularly with propofol) in the ICU to achieve the same goals. The clinical and literature experience with remifentanil, an ultra-short acting opioid (by virtue of esterase metabolism), is limited. [7] Pulmonary accumulation or extraction characteristic of other opioids is absent. [8] Its "lightning-fast" kinetics may work well in some settings but not in others. Clearly a reliable drug delivery system is mandatory (preferably with monitoring of the bispectral index). This agent may offer distinct advantages in "off-pump", minimally invasive procedures, in which the "confounding effects" on wakeup of pump and systemic inflammatory effects are minimized.

Although we all have a "moral obligation" to minimize perioperative expense, at the present time there is no convincing evidence demonstrating that small scale reductions in per patient cost reduce overall hospital costs! Anesthetic drugs comprise a small percentage of cardiac surgery costs. Twice the cost between a "routine" or a "SAFE" anesthetic is inconsequential. In fact, these costs are small compared to that of aprotinin which is being used "liberally" (i.e in primary cases "at risk" for bleeding) in many centers! The major outliers in cost remain perioperative complications. [9, 10] Although the majority of these are closely or exclusively related to the surgical procedure itself (i.e. infarction, low output syndromes, renal failure, infection, etc.), we cannot discount the possibility that some are at least in part related to anesthetic management. Early postoperative residual drug effects may have a direct effect on time to extubation. After extubation they may modulate clinical or subclinical pulmonary complications and adversely impact on accelerated recovery. A single complication of this kind can offset all of the drug cost savings for an entire year at a given institution.

Have previous large-scale randomized cardiac anesthesia studies proven "its not what you use, but how you use it"? The dated pre-Fast Track studies of Slogoff and Keats and Tuman et. al. supported this notion, but due to well documented weakness in experimental design, failed to prove the point. [11, 12] A later pre-Fast Track randomized study by Mora et. al. supports the concept that a (more expensive) propofol-based anesthetic is associated with earlier awakening. [13] The recent observational study of Butterworth et. using "mixed-effects" logistic regression modeling of a 40 hospital "benchmarking" data-set, suggests little effect of use of sufentanil (over fentanyl) or vecuronium (over pancuronium) on ICU or total length of stay (after adjustment for patient risk and hospital level effects). [14] Yet, sufentanil use was associated with a 1.9 hr. reduction in time to extubation. This study fails to consider a host of other important factors (including drug doses or use of benzodiazepines or inhalational agents) as well as the presence or absence of a Fast Track program at a given hospital! I believe it fails to make a convincing argument on this issue. We are currently analyzing a larger prospective, observational data-set with more detailed anesthesia and Fast Tracking data in 14 Veterans Affairs hospitals. [15]

SAFE anesthetics, despite their increased cost, constitute a small percentage of total perioperative costs. Present literature has neither proven nor disproven that older drugs are equivalent to SAFE agents. In a dynamic, rapidly evolving, "high stakes" environment, restricting the anesthesiologist's pharmacologic armamentarium required to provide predictable clinical results is truly "penny wise but pound foolish"!

References:

1. Reves JG, Sladen RN, Newman MF: Cardiac anesthetic: is it unique?. Anesth Analg 1995;81:895-6

2. Cheng DC: Fast track cardiac surgery pathways: early extubation, process of care, and cost containment. Anesthesiology 1998;88:1429-33

3. Hall RI: Anaesthesia for coronary artery surgery--a plea for a goal-directed approach . Can J Anaesth 1993;40:1178-94

4. Glass PS: Pharmacokinetic and pharmacodynamic principles in providing "fast-track" recovery. J Cardiothorac Vasc Anesth 1995;9:16-20

5. Shafer SL, Varvel JR: Pharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology 1991;74:53-63

6. London MJ, Shroyer AL, Coll JR, et. al.: Early extubation following cardiac surgery in a veterans population. Anesthesiology 1998;88:1447-58

7. Burkle H, Dunbar S, Van Aken H: Remifentanil: a novel, short-acting, mu-opioid. Anesthesia & Analgesia 1996;83:646-51

8. Duthie DJ, Stevens JJ, Doyle AR, et. al.: Remifentanil and pulmonary extraction during and after cardiac anesthesia. Anesth Analg 1997;84:740-4

9. Taylor GJ, Mikell FL, Moses HW, et. al.: Determinants of hospital charges for coronary artery bypass surgery: the economic consequences of postoperative complications. Am J Cardiol 1990;65:309-13

10. Kalish RL, Daley J, Duncan CC, et. al.: Costs of potential complications of care for major surgery patients. Am J Med Qual 1995;10:48-54

11. Tuman KJ, McCarthy RJ, Spiess BD, et. al.: Does choice of anesthetic agent significantly affect outcome after coronary artery surgery? Anesthesiology 1989;70:189-98

12. Slogoff S, Keats AS: Randomized trial of primary anesthetic agents on outcome of coronary artery bypass operations. Anesthesiology 1989;70:179-88

13. Mora CT, Dudek C, Torjman MC, et. al.: The effects of anesthetic technique on the hemodynamic response and recovery profile in coronary revascularization patients. Anesth Analg 1995;81:900-10

14. Butterworth J, James R, Prielipp RC, et. al.: Do shorter-acting neuromuscular blocking drugs or opioids associate with reduced intensive care unit or hospital lengths of stay after coronary artery bypass grafting? CABG Clinical Benchmarking Data Base Participants. Anesthesiology 1998;88:1437-46

15. London MJ, Shroyer AL, Grover FL, et. al.: Evaluating anesthesia health care delivery for cardiac surgery. The role of process and structure variables. Medical Care 1995;33:OS66-75

CON: Use of Short-Acting Neuromuscular Blocking (NMB) Drugs and Narcotics Reduce ICU Time and Hospital Length of Stay after Coronary Artery Bypass Graft Surgery.

Richard C. Prielipp, MD

John F. Butterworth, MD

Department of Anesthesiology

Wake Forest University

School of Medicine

Winston-Salem, NC

Hospitals and physicians employ a variety of strategies to reduce costs while maintaining or improving outcomes for coronary artery bypass graft (CABG) patients. It is assumed commonly that extensive use of newer, shorter-acting anesthetic/narcotics (e.g., sufentanil) and NMB drugs (e.g., vecuronium) results in "fast-track" passage of patients through the ICU and postoperative ward after CABG surgery.¹ However, the actual factors which predict duration of intubation, ICU and hospital lengths of stay (LOS) are not well established. We,² and others,³ contend that it is the perioperative process of care (i.e., one which relies on multidisciplinary physician input with integrated institutional support), rather than the choice of anesthetic drugs, which determines the efficiency of any given recovery pathway.

Academic Benchmark Data⁴

Use of benchmark data provides a rapid "snapshot" of contemporaneous clinical practice, and we therefore examined university benchmark data on 1,094 adult patients undergoing CABG surgery at 40 academic health centers. These data tested specific "fast-track" hypotheses:²

use of vecuronium promotes early extubation and shorter lengths of stay (LOS) after CABG surgery compared to the longer-acting pancuronium; and

use of the shorter-acting narcotic sufentanil rather than the longer-acting fentanyl similarly promotes early extubation and shorter LOS.

The methodology of data collection and analysis are detailed previously.^2,4 As expected, patient-related factors such as increasing age, increasing weight, decreasing left-ventricular ejection fraction, history of congestive heart failure, chronic lung disease, renal failure, diabetes mellitus, and Diagnosis-Related Group (DRG 106, cardiac catheterization plus CABG) predict worsening of outcome measures such as the duration of endotracheal intubation in the ICU (Table 1). Other results which examine the influence of anesthetic drugs and "fast-track" protocols are noted below.

NMB Drugs: Compared to pancuronium, use of vecuronium was not associated with significant reductions in duration of intubation, or ICU and hospital LOS (Table 2). On the other hand, some clinicians might still suggest that effects of various NMB drugs on heart rate and blood pressure justifies use of one agent vs. another; i.e., use of vecuronium over pancuronium for patients with coronary artery disease. However, we have not been able to identify such advantages in actual clinical practice using fentanyl-based cardiac anesthesia. We previously compared pancuronium to vecuronium,⁵ as well as to pipecuronium and doxacurium,⁶ and found pancuronium to require fewer drug interventions to control heart rate and blood pressure compared to the other NMB drugs.^5,6

Opioids: While use of sufentanil (compared to fentanyl) resulted in a statistically significant (P=0.03) reduction of 2 hours in duration of intubation (Table 2), this did not translate into a significant decrease in other measures of resource utilization. The explanation for this 2 hour time difference is not defined by benchmark data, and could include factors such as anesthesiologist practice patterns and perception of potency, ICU personnel expectations for ventilator weaning, as well as actual pharmacokinetic characteristics of these two opioids.

Gender: Female sex had a significant influence on postoperative resource utilization, even after all other covariates had been included in the analysis.⁷ Previous investigations have touted factors such as age or body size for the sex-related outcome differences.⁸ For instance, females tend to develop coronary artery disease later in life, have more diffuse coronary artery disease, and are more likely to have diabetes mellitus. Nonetheless, we were surprised to find women had significantly longer durations of intubation and ICU LOS than men, even after we controlled for weight, age, diabetes, and other variables. This suggests that women may have some previously unidentified greater sensitivity than men to sufentanil or fentanyl, or anesthesiologists may dose these narcotics differently in women relative to men. Lastly, other factors such as number of brain microemboli or severity of brain edema may be worse in women.

Summary

We found no evidence that use of the shorter-acting opioids and NMB drugs lead to shorter ICU or hospital LOS, or decrease resource utilization. Despite a number of plausible positive attributes of vecuronium in CABG surgery patients, in actual practice, patients receiving the less expensive, longer-acting pancuronium were just as likely to undergo early extubation and "fast-track" through the ICU.² While use of sufentanil rather than fentanyl did reduce intubation duration by two hours, we could not correlate this small difference with any effect on ICU or hospital LOS, or utilization of hospital resources. Contrary to one's intuition, factors related to severity of patient illness or choice of anesthetic drugs did not account for the large variation observed among institutions in ICU utilization and LOS.^2,7 We attribute the majority of this variation to subtle, but important, differences in clinical practice and institutional organization. Indeed, the institution in which a patient undergoes CABG has a very significant (P=0.0001) influence on all these outcome variables and LOS. The marked inter-institutional variability suggests that substantial reductions in LOS and costs are best accomplished through an efficient accelerated recovery program which coordinates the efforts of physicians, nurses, patients, and families throughout the perioperative period (integrated model).³ A focus on which opioid or NMB drug is utilized during cardiac anesthesia will be much less rewarding.

References

1. Engelman RM, Rousou JA, Flack JE III, Deaton DW, Humphrey CB, Ellison LH, Allmendinger PD, Owen SG, Pekow PS. Fast-track recovery of the coronary bypass patient. Ann Thorac Surg 1994; 58:1742-46

2. Butterworth JF, James R, Prielipp RC, Cerese J, Livingston J, Burnett DA, and the CABG Clinical Benchmarking Data Base Participants. Do shorter-acting neuromuscular blockers or narcotics reduce critical care utilization or hospital length of stay after coronary artery bypass grafting? Anesthesiology 1998; 88:1437-58

3. Cheng DCH. Fast Track cardiac surgery pathways (editorial). Anesthesiology 1998; 88:1429-33

4. Clinical Process Improvement Program. Clinical process improvement: coronary artery bypass graft (CABG) clinical benchmarking data base. Report #2. Oakbrook, IL: University HealthSystem Consortium Services Corp: Clinical Practice Advancement Center, 1996.

5. Gravlee GP, Ramsey FM, Roy RC, Angert KC, Rogers AT, Pauca AL. Rapid administration of a narcotic and neuromuscular blocker: a hemodynamic comparison of fentanyl, sufentanil, pancuronium, and vecuronium. Anesth Analg 1988; 67:39-47

6. Rathmell JP, Brooker RF, Prielipp RC, Butterworth JF IV, Gravlee GP. Hemodynamic and pharmacodynamic comparison of doxacurium and pipecuronium with pancuronium during induction of cardiac anesthesia: does the benefit justify the cost? Anesth Analg 1993; 76:513-19

7. Butterworth J, James R, Prielipp R, Cerese J, Livingston J, Burnett D. Influence of female sex on resource utilization after coronary artery surgery (abstract). Anesthesiology 1997; 87(3A):A124

8. Christakis GT, Weisel RD, Buth KJ, Fremes SE, Rao V, Panagiotopoulos KP, Ivanov J, Goldman BS, David TE. Is body size the cause for poor outcomes of coronary artery bypass operations in women? J Thorac Cardiovasc Surg 1995; 110:1344-58

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