THE paper by Wallace et al.1
in this issue of Anesthesiology offers an important contribution to a field that has recently been through a very stormy period.
In the early 1970s, it was recognized that β-blockade was compatible with anesthesia and offered the advantage of hemodynamic stability at the time of sympathetic stimulation—in addition to reducing the risk of myocardial ischemia and ventricular arrhythmias.2
This reduction of the risk of perioperative myocardial ischemia,3,4
arrhythmias, and myocardial infarction5
was confirmed in later studies.
A decade later, two randomized controlled trials showed improved survival with perioperative β-blockade6
as well as reduced risk of death and myocardial infarction in the short- and long-term,7,8
and also reduced incidence of silent myocardial ischemia.9
Data from both studies were reported, in part, in two papers. Both studies have limitations in their applicability to general noncardiac surgical populations, however; one was a subset of patients from a cohort of 1,350 patients that enrolled only those with reversible ischemia,7
and the other had a high incidence of diabetes mellitus in the control group. In addition, some patients had their β-blocker stopped before randomization, and in-hospital deaths were ignored in the analysis.6
Based on the available evidence, the American College of Physicians9
in 1996, followed by the American College of Cardiology and the American Heart Association10
in 1997, recommended β-blockers before noncardiac surgery in all patients with overt coronary artery disease or risk factors for it.10,11
Indeed, it appeared to some authors that perioperative β-blockade was one of the practices that most improved patient safety.12
A number of randomized controlled trials were carried out, some with positive and some with equivocal results.6,7,13–18
Meta-analyses based on a small number of studies confirmed the efficacy of β-blockade in the prevention of perioperative cardiac complications,19,20
but those that included a much larger number of studies in noncardiac21
in addition to combined cardiac and noncardiac surgery22
found no statistically significant benefits. Over time, guidelines insisted on the need to consider β-blockers in patients at risk (i.e.
, high-risk surgery, high risk of coronary artery disease) rather than all patients at risk for coronary artery disease. A more cautious approach was recommended.23,24
Then came the thunderbolt. It appeared in the form of the PeriOperative ISchemic Evaluation (POISE) Trial.25
The trial's data showed that perioperative β-blockade significantly reduced the incidence of cardiac events—but at the price of increased
risk of all-cause mortality and major strokes. Not surprisingly, the study attracted a large number of comments in respect of the choice and dose of β-blocker, the time treatment was initiated, and the heart rate and blood pressure thresholds for the administration of the next dose of the β-blocker.26–28
The POISE findings were echoed in meta-analysis by Bangalore et al.
such that the case for perioperative β-blockade was suspect.29
Preliminary analysis of the POISE data suggested that arterial hypotension was an important correlate of stroke and all-cause death.25
However, a factor not investigated in POISE—or other studies to date—may have been the presence of preexisting anemia, including that due to acute blood loss. Indeed, experimental and clinical data have shown that β-blockade has important detrimental effects on the brain in the presence of anemia.30,31
During the perioperative period, the current trend for accepting a lower hemoglobin concentration as threshold for blood transfusion may play a role in the development of adverse cerebral events in the face of β-blockade.
Two sets of guidelines were published in November 2009, one on behalf of the American College of Cardiology Foundation and the American Heart Association,32
the other on behalf of the European Society of Cardiology.33
Both contain recommendations on the perioperative use of β-blockers. Both advocate starting treatment at least 1 week (preferably 30 days) before surgery and adjusting the effects to appropriate heart rates and blood pressures. They also both advocate maintaining β-blockade in patients already on this medication. Both sets of guidelines were prepared before the positive results of the most recent randomized controlled trial—The Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study, DECREASE IV—were published.34
Because these two sets of guidelines differ, the American College of Cardiology Foundation/American College of Cardiology recommendations being generally more restrictive than those of the European Society of Cardiology, the paper by Wallace et al
Although randomized controlled trials may be the best evidence there is, they unavoidably contain a built-in degree of artificiality with their inclusion/exclusion criteria and strict protocols for drug administration. Such restrictions make “real-world” epidemiologic analysis particularly important. Yet, even these studies, undoubtedly, have their limitations. In the case of Wallace et al
the data were collected in a department known for its interest in myocardial ischemia and cardiac protection. The study was a natural extension of earlier work to develop a program for perioperative β-blockade: the Perioperative Cardiac Risk Reduction Therapy Protocol, PCRRT. Patients were considered for inclusion if they had proven coronary artery disease, previous or current vascular surgery, or two of the following risk factors: diabetes mellitus, hypertension, age older than 60 yr, smoking, or hyperlipidemia. Such inclusion criteria are very similar to those of POISE, but completely different from DECREASE,7
because the latter study included only patients with reversible ischemia on a stress test.
Further, the data presented by Wallace et al.1
include 38,779 operations over 12 yr and reveal an almost equal number of operations in patients taking (52%) versus
not taking (48%) a β-blocker. Over a 1-yr period, survival rates were equal in those who were started on a β-blocker at the time of surgery and those in whom this therapeutic regimen was continued. This holds true for all types of surgeries, though the data may show only trends in the case of relatively small subgroups. This is important information because cardiac protection by long-term β-blockade has not been universally reported,35
possibly because β-blockade in previous studies was either not reliably given during surgical admission or the dose was inadequate to ensure cardiac protection. The study of Wallace et al.1
therefore supports the accepted policy of maintaining treatment with β-blockers throughout the perioperative period, a policy based hitherto on relatively limited evidence.36,37
At 30 days and 1 yr the benefits of maintaining β-blockade were seen in the higher risk patients (i.e.
, class 2-6 per Revised Cardiac Risk Index38
) and in all types of surgeries. Maintenance of β-blockade must be associated with appropriate dosing protocols to avoid hypotension, which was an important determinant of adverse outcomes in POISE.25
The importance of maintaining β-blocker therapy in patients undergoing noncardiac surgery has also been emphasized by the recent observational study of van Klei et al.39
in orthopedic surgical patients.
When considering the benefits versus
risks of β-blockade, interactions between β-blockade and other concurrent therapies and comorbidities need to be evaluated. In many recent studies of perioperative β-blockade, the continued administration of concomitant cardiovascular drugs is often not specified. This factor may be especially relevant in the case of statins, because their continuation is known to be beneficial and their withdrawal is associated with increased morbidity.40
During studies of long duration, it is likely that an increasingly large proportion of patients received statins. Wallace et al.1
introduced clonidine in their protocol, an addition that may, therefore, have played a role in the degree of protection offered by the initiation of β-blockade.
What the study by Wallace et al.1
also shows is that absence of β-blockade—either through nonadministration as a result of clinician's choice or active drug withdrawal—is associated with reduced survival. The study confirms that β-blockade withdrawal is associated with significantly worse outcomes even in the lowest risk patients.
The recent guidelines insist on starting β-blockade at least 1 week before surgery.32,33
This was not the case with the PCRRT protocol; β-blockade, when added at the time of surgery, was started the day of surgery. This was the case for 5,832 operations. However, the addition of a β-blocker in this manner proved better than no β-blockade. The concept of starting β-blockade long before surgery is logical, but not always practical. Moreover, very few randomized controlled trials have used this approach,7,34,41
including, to a limited but unspecified extent, the Perioperative β-Blockade or POBBLE study.15
The total number of patients is only 662 in all these studies. This is in contrast to the 6,474 patients who received a β-blocker immediately before surgery as reported in the meta-analysis by Bangalore et al.29
—and now the 5,832 operations reported by Wallace et al.1
in this issue of the Journal. The evidence for starting β-blockade several weeks before surgery is, therefore, not firmly established. Not surprisingly, over the 12 yr of the Wallace et al.
study, there was an increase in the proportion of patients who continued with β-blockers and a decrease in those who did not receive them.
What are the messages of the paper by Wallace et al
.? What should the clinician do now? As for any treatment, β-blockade has to be considered from a risk/benefit perspective. With or without studies, it stands to reason that at-risk patients are likely to benefit more, as was shown by Lindenauer et al.42
in the largest observational cohort of β-blockade in surgical patients ever published. The Wallace et al.1
data show that the addition or continuation of β-blockade reduced mortality in higher risk patients. As with all potent agents, there is need for protocols that address initiation and administration of successive doses, especially in the face of the hemodynamic instability that characterizes major surgery and recovery. The current European Society of Cardiology guideline suggests that 100 mmHg systolic arterial pressure is sufficient for the next dose to be given, whereas American College of Cardiology Foundation/American College of Cardiology guideline indicates that the next dose should be given in the absence of hypotension
. Wallace et al.
in their protocol, required a systolic arterial pressure of more than 120 mmHg. Although either 100 or 120 mmHg may be appropriate in most patients, this threshold may not be sufficient in the case of patients with hypertensive heart disease. We believe that, in these circumstances, any protocols will need to be adjusted to reflect the likely changes in autoregulatory mechanisms.
In view of the current controversies, the Wallace et al.1
study has the merit of confirming in a large cohort that withdrawal of β-blockade is dangerous; conversely, maintenance of β-blockade or its initiation at the time of surgery confers cardiovascular protection; and the absence of β-blockade in at-risk patients increases the risk of adverse cardiac events.
Thus, the case for perioperative β-blockade in noncardiac surgical patients, as questioned by the findings of POISE, has been partially reestablished. What is needed now are more studies answering the issues of when is best to start treatment and for how long; whether one class of β-blockers has greater risk-benefit advantage; which route of perioperative administration is preferable43
; and, most importantly, how best to maintain careful monitoring of these patients in the preoperative, perioperative, and postoperative periods with active treatment of any adverse effects. In this way, the cardioprotective utility of an important class of drugs in the perioperative period is likely to be enhanced.
Pierre Foëx, M.D., D.Phil., F.R.C.A., F.A.N.Z.C.A., F.C.A.(S.A.), F.Med.Sci.*
John W. Sear, B.Sc., Ph.D., M.B.B.S., F.F.A.R.C.S., F.A.N.Z.C.A.†
*Nuffield Department of Anaesthetics, University of Oxford, Oxford, United Kingdom. email@example.com. †Department of Anaesthetics, University of Oxford.
1. Wallace AW, Au S, Cason BA: Association of the pattern of use of perioperative β-blockade and postoperative mortality. Anesthesiology 2010; 113:794–805
2. Prys-Roberts C, Foëx P, Biro GP, Roberts JG: Studies of anaesthesia in relation to hypertension. V. Adrenergic beta-receptor blockade. Br J Anaesth 1973; 45:671–81
3. Stone JG, Foëx P, Sear JW, Johnson LL, Khambatta HJ, Triner L: Myocardial ischemia in untreated hypertensive patients: Effect of a single small oral dose of a β-adrenergic blocking agent. Anesthesiology 1988; 68:495–500
4. Pasternack PF, Grossi EA, Baumann FG, Riles TS, Lamparello PJ, Giangola G, Primis LK, Mintzer R, Imparato AM: Beta blockade to decrease silent myocardial ischemia during peripheral vascular surgery. Am J Surg 1989; 158:113–6
5. Pasternack PF, Imparato AM, Baumann FG, Laub G, Riles TS, Lamparello PJ, Grossi EA, Berguson P, Becker G, Bear G: The hemodynamics of beta-blockade in patients undergoing abdominal aortic aneurysm repair. Circulation 1987; 76:III1–7
6. Mangano DT, Layug EL, Wallace A, Tateo I: Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med 1996; 335:1713–20
7. Poldermans D, Boersma E, Bax JJ, Thomson IR, van de Ven LL, Blankensteijn JD, Baars HF, Yo TI, Trocino G, Vigna C, Roelandt JR, van Urk H: The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 1999; 341:1789–94
8. Poldermans D, Boersma E, Bax JJ, Thomson IR, Paelinck B, van de Ven LL, Scheffer MG, Trocino G, Vigna C, Baars HF, van Urk H, Roelandt JR, Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group: Bisoprolol reduces cardiac death and myocardial infarction in high-risk patients as long as 2 years after successful major vascular surgery. Eur Heart J 2001; 22:1353–8
9. Wallace A, Layug B, Tateo I, Li J, Hollenberg M, Browner W, Miller D, Mangano DT: Prophylactic atenolol reduces postoperative myocardial ischemia. McSPI Research Group. Anesthesiology 1998; 88:7–17
10. Eagle KA, Brundage BH, Chaitman BR, Ewy GA, Fleisher LA, Hertzer NR, Leppo JA, Ryan T, Schlant RC, Spencer WH 3rd, Spittell JA Jr, Twiss RD, Ritchie JL, Cheitlin MD, Gardner TJ, Garson A Jr, Lewis RP, Gibbons RJ, O'Rourke RA, Ryan TJ: Guidelines for perioperative cardiovascular evaluation for noncardiac surgery. Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). J Am Coll Cardiol 1996; 27:910–48
11. Palda VA, Detsky AS: Perioperative assessment and management of risk from coronary artery disease. Ann Intern Med 1997; 127:313–28
12. Leape LL, Berwick DM, Bates DW: What practices will most improve safety? Evidence-based medicine meets patient safety. JAMA 2002; 288:501–7
13. Bayliff CD, Massel DR, Inculet RI, Malthaner RA, Quinton SD, Powell FS, Kennedy RS: Propranolol for the prevention of postoperative arrhythmias in general thoracic surgery. Ann Thorac Surg 1999; 67:182–6
14. Urban MK, Markowitz SM, Gordon MA, Urquhart BL, Kligfield P: Postoperative prophylactic administration of beta-adrenergic blockers in patients at risk for myocardial ischemia. Anesth Analg 2000; 90:1257–61
15. Brady AR, Gibbs JS, Greenhalgh RM, Powell JT, Sydes MR, POBBLE trial investigators: Perioperative beta-blockade (POBBLE) for patients undergoing infrarenal vascular surgery: Results of a randomized double-blind controlled trial. J Vasc Surg 2005; 41:602–9
16. Juul AB, Wetterslev J, Gluud C, Kofoed-Enevoldsen A, Jensen G, Callesen T, Nørgaard P, Fruergaard K, Bestle M, Vedelsdal R, Miran A, Jacobsen J, Roed J, Mortensen MB, Jørgensen L, Jørgensen J, Rovsing ML, Petersen PL, Pott F, Haas M, Albret R, Nielsen LL, Johansson G, Stjernholm P, Mølgaard Y, Foss NB, Elkjaer J, Dehlie B, Boysen K, Zaric D, Munksgaard A, Madsen JB, Øberg B, Khanykin B, Blemmer T, Yndgaard S, Perko G, Wang LP, Winkel P, Hilden J, Jensen P, Salas N, DIPOM Trial Group: Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: Randomised placebo controlled, blinded multicentre trial. BMJ 2006; 332:1482–5
17. Yang H, Raymer K, Butler R, Parlow J, Roberts R: The effects of perioperative beta-blockade: Results of the Metoprolol after Vascular Surgery (MaVS) study, a randomized controlled trial. Am Heart J 2006; 152:983–90
18. Neary WD, McCrirrick A, Foy C, Heather BP, Earnshaw JJ: Lessons learned from a randomised controlled study of perioperative beta blockade in high risk patients undergoing emergency surgery. Surgeon 2006; 4:139–43
19. Auerbach AD, Goldman L: Beta-blockers and reduction of cardiac events in noncardiac surgery: Scientific review. JAMA 2002; 287:1435–44
20. Stevens RD, Burri H, Tramèr MR: Pharmacologic myocardial protection in patients undergoing noncardiac surgery: A quantitative systematic review. Anesth Analg 2003; 97:623–33
21. Devereaux PJ, Beattie WS, Choi PT, Badner NH, Guyatt GH, Villar JC, Ciná CS, Leslie K, Jacka MJ, Montori VM, Bhandari M, Avezum A, Cavalcanti AB, Giles JW, Schricker T, Yang H, Jakobsen CJ, Yusuf S: How strong is the evidence for the use of perioperative beta blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials. BMJ 2005; 331:313–21
22. Wiesbauer F, Schlager O, Domanovits H, Wildner B, Maurer G, Muellner M, Blessberger H, Schillinger M: Perioperative beta-blockers for preventing surgery-related mortality and morbidity: A systematic review and meta-analysis. Anesth Analg 2007; 104:27–41
23. Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE, Freeman WK, Froehlich JB, Kasper EK, Kersten JR, Riegel B, Robb JF, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R, Page RL, Riegel B, American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Committee to Update the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology: ACC/AHA 2006 guideline update on perioperative cardiovascular evaluation for noncardiac surgery: Focused update on perioperative beta-blocker therapy: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society for Vascular Medicine and Biology. Circulation 2006; 113:2662–74
24. Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE, Freeman WK, Froehlich JB, Kasper EK, Kersten JR, Riegel B, Robb JF, ACC/AHA TASK FORCE MEMBERS, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Buller CE, Creager MA, Ettinger SM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Md RN, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW: ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): Developed in Collaboration With the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. Circulation 2007; 116:1971–96
25. Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, Villar JC, Xavier D, Chrolavicius S, Greenspan L, Pogue J, Pais P, Liu L, Xu S, Málaga G, Avezum A, Chan M, Montori VM, Jacka M, Choi P, POISE Study Group: Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): A randomised controlled trial. Lancet 2008; 371:1839–47
26. Fleisher LA, Poldermans D: Perioperative beta blockade: Where do we go from here? Lancet 2008; 371:1813–4
27. London MJ: Quo vadis, perioperative beta blockade? Are you “POISE'd” on the brink? Anesth Analg 2008; 106:1025–30
28. Sear JW, Giles JW, Howard-Alpe G, Foëx P: Perioperative beta-blockade, 2008: What does POISE tell us, and was our earlier caution justified? Br J Anaesth 2008; 101:135–8
29. Bangalore S, Wetterslev J, Pranesh S, Sawhney S, Gluud C, Messerli FH: Perioperative beta blockers in patients having non-cardiac surgery: A meta-analysis. Lancet 2008; 372:1962–76
30. Ragoonanan TE, Beattie WS, Mazer CD, Tsui AK, Leong-Poi H, Wilson DF, Tait G, Yu J, Liu E, Noronha M, Dattani ND, Mitsakakis N, Hare GM: Metoprolol reduces cerebral tissue oxygen tension after acute hemodilution in rats. Anesthesiology 2009; 111:988–1000
31. Beattie WS, Wijeysundera DN, Karkouti K, McCluskey S, Tait G, Mitsakakis N, Hare GM: Acute surgical anemia influences the cardioprotective effects of β-blockade: A single-center, propensity-matched cohort study. Anesthesiology 2010; 112:25–33
32. Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof EL, Fleischmann KE, Freeman WK, Froehlich JB, Kasper EK, Kersten JR, Riegel B, Robb JF: 2009 ACCF/AHA focused update on perioperative beta blockade incorporated into the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: A report of the American college of cardiology foundation/American heart association task force on practice guidelines. Circulation 2009; 120:e169–276
33. Poldermans D, Bax JJ, Boersma E, De Hert S, Eeckhout E, Fowkes G, Gorenek B, Hennerici MG, Iung B, Kelm M, Kjeldsen KP, Kristensen SD, Lopez-Sendon J, Pelosi P, Philippe F, Pierard L, Ponikowski P, Schmid JP, Sellevold OF, Sicari R, Van den Berghe G, Vermassen F, Hoeks SE, Vanhorebeek I, Vahanian A, Auricchio A, Bax JJ, Ceconi C, Dean V, Filippatos G, Funck-Brentano C, Hobbs R, Kearney P, McDonagh T, McGregor K, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Vardas P, Widimsky P, De Caterina R, Agewall S, Al Attar N, Andreotti F, Anker SD, Baron-Esquivias G, Berkenboom G, Chapouotot L, Cifkova R: Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery: The Task Force for Preoperative Cardiac Risk Assessment and Perioperative Cardiac Management in Non-cardiac Surgery of the European Society of Cardiology (ESC) and endorsed by the European Society of Anaesthesiology (ESA). Eur Heart J 2009; 30:2769–812
34. Dunkelgrun M, Boersma E, Schouten O, Koopman-van Gemert AW, van Poorten F, Bax JJ, Thomson IR, Poldermans D, Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group: Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery: A randomized controlled trial (DECREASE-IV). Ann Surg 2009; 249:921–6
35. Giles JW, Sear JW, Foëx P: Effect of chronic beta-blockade on peri-operative outcome in patients undergoing non-cardiac surgery: An analysis of observational and case control studies. Anaesthesia 2004; 59:574–83
36. Shammash JB, Trost JC, Gold JM, Berlin JA, Golden MA, Kimmel SE: Perioperative beta-blocker withdrawal and mortality in vascular surgical patients. Am Heart J 2001; 141:148–53
37. Hoeks SE, Scholte Op Reimer WJ, van Urk H, Jörning PJ, Boersma E, Simoons ML, Bax JJ, Poldermans D: Increase of 1-year mortality after perioperative beta-blocker withdrawal in endovascular and vascular surgery patients. Eur J Vasc Endovasc Surg 2007; 33:13–9
38. Lee TH, Marcantonio ER, Mangione CM, Thomas EJ, Polanczyk CA, Cook EF, Sugarbaker DJ, Donaldson MC, Poss R, Ho KK, Ludwig LE, Pedan A, Goldman L: Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999; 100:1043–9
39. van Klei WA, Bryson GL, Yang H, Forster AJ: Effect of β-blocker prescription on the incidence of postoperative myocardial infarction after hip and knee arthroplasty. Anesthesiology 2009; 111:717–24
40. Le Manach Y, Coriat P, Collard CD, Riedel B: Statin therapy within the perioperative period. Anesthesiology 2008; 108:1141–6
41. Magnusson J, Thulin T, Werner O, Järhult J, Thomson D: Haemodynamic effects of pretreatment with metoprolol in hypertensive patients undergoing surgery. Br J Anaesth 1986; 58:251–60
42. Lindenauer PK, Pekow P, Wang K, Mamidi DK, Gutierrez B, Benjamin EM: Perioperative beta-blocker therapy and mortality after major noncardiac surgery. N Engl J Med 2005; 353:349–61
43. Gosgnach M, Aymard G, Huraux C, Fléron MH, Coriat P, Diquet B: Atenolol administration via a nasogastric tube after abdominal surgery: An unreliable route. Anesth Analg 2005; 100:137–40
© 2010 American Society of Anesthesiologists, Inc.