Does perioperative thyroxine have a role during adult cardiac surgery
http://www.100md.com
《血管的通路杂志》
a Department of Cardiac Anaesthesia, Aberdeen Royal Infirmary, Aberdeen, UK
b Department of Cardiothoracic Surgery, James Cook University Hospital, Middlesbrough, UK
Abstract
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether the use of prophylactic perioperative thyroxine therapy during cardiopulmonary bypass in the euthyroid adult patient undergoing routine cardiac surgery can result in an improved cardiac output leading to better clinical outcomes. Altogether 86 papers were identified on Medline and 113 on Embase using the reported search. A further paper was identified by hand-searching of reference lists. Thirteen papers represented the best evidence on the topic. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses were tabulated. We conclude that it is clear that triiodothyronine levels decrease by 50% or more during cardiopulmonary bypass. However, there is conflicting evidence that prophylactic perioperative thyroxine/triiodothyronine therapy is a useful inotropic adjunct in adult patients undergoing routine cardiac surgery and whilst some studies report improved haemodynamic parameters in the immediate post-bypass period there is no evidence that its use influences postoperative morbidity, mortality or length of stay in the elective patient. It may, however, have a role as rescue therapy in supporting some high risk cases during weaning from CPB or bridging to LVAD or transplant.
Key Words: Cardiac surgery; Thyroxine; Triiodothyronine; Postoperative outcomes; Review; Evidence based medicine
1. Introduction
A best evidence topic was constructed according to the structured protocol. This protocol is fully described in the ICVTS [1].
2. Clinical scenario
You are anaesthetising a high risk CABG patient. Before coming off bypass, the surgeon requests that you give some thyroxine. You have never heard of this strategy before and thus, while you give the thyroxine, you decide to review the literature to see if there is any evidence to back up this strategy.
3. Three-part question
In [patients undergoing cardiac surgery], is the use of [thyroxine] associated with [improved cardiac output, better recovery or fewer complications].
4. Search strategy
Medline 1966 to November 2005 using OVID interface, EMBASE 1980 to 2005 Week 52.
[exp Cardiopulmonary Bypass OR CABG.mp. OR exp Thoracic Surgery OR exp Cardiac surgical procedures OR Coronary art$ bypass.mp. OR Cardiopulmonary bypass.mp. OR exp Cardiovascular Surgical Procedures/OR exp Thoracic Surgical Procedures/OR exp Coronary Artery Bypass/OR cardiac transplantation.mp. OR exp Heart Transplantation/] AND [exp Thyroxine/OR Thyroxine.mp. OR exp Triiodothyronine/OR triiodothyronine.mp. OR thyronine.mp. OR exp Thyronines/] AND [exp Cardiac Output/ph, de, su, th OR exp Hemodynamic Processes/OR haemodynamic processes.mp. OR postoperative care.mp. OR exp Postoperative Care/OR exp Anesthesia Recovery Period/OR exp "Recovery of Function"/OR exp Intraoperative Complications/OR exp Postoperative Complications/OR surgical complications.mp. OR Postoperative Complications.mp OR Length of Stay.mp].
5. Search outcome
A total of 86 papers on Medline and 113 on Embase were identified using the reported search. A further relevant paper was identified by hand searching reference lists. Thirteen papers represented the best evidence on the subject and are summarised in Table 1.
6. Results
It is well recognised that decreased thyroxine hormone levels accompanying cardiopulmonary bypass (CPB) can be reversed by thyroxine or triiodothyronine (T3) administration before or during bypass [2–6]. But whilst some studies have shown that this strategy can improve cardiac output there is little evidence that recovery is enhanced and complications decreased.
Several authors have identified some short-term haemodynamic benefits following T3 or thyroxine administration during cardiac surgery. Sirlak et al. gave oral T3 both preoperatively and postoperatively and found significant differences in cardiac index (CI) and systemic vascular resistance (SVR) with decreased inotrope and IABP requirements [2]. But whilst ITU stay was less, there was no significant difference in myocardial ischaemia/infarction rate, atrial fibrillation or death. Novitsky et al. found T3 administration on bypass decreased inotrope and diuretic requirement in patients with ejection fraction (EF) less than 30% although there was no difference in haemodynamic data [3]. Their T3 regime was subsequently modified on the basis of data from this study and repeated in patients with higher ejection fractions. Whilst there was no difference in inotrope or diuretic use in this latter group, cardiac output (CO) was significantly higher and SVR and pulmonary vascular resistance (PVR) lower in their T3-treated group [3]. Mullis–Jansson et al. reported similar improvements in CI in their male cohort following T3 administration at cross-clamp release although both sexes experienced decreased myocardial ischaemia, inotrope dependence/requirement and need for mechanical support [7]. However, their control group was significantly older than their T3-group possibly confounding some of their findings [7]. Finally, Klemperer et al. noted that T3 administration in patients with impaired LV function significantly increased CI and decreased SVR for the first 6 h post-cross clamp removal [4] but found no significant differences in interventions required to support separation from CPB, postoperative inotrope use, duration of postoperative ventilation, ITU or hospital stay, or overall morbidity and mortality. However, whilst this study demonstrated comparable incidences of supraventricular and ventricular dysrhythmias in the first 18 h a subsequent paper by the same authors reported decreased prevalence and incidence of atrial fibrillation (AF) in the T3-treated cohort monitored beyond 24 h [8]. Significantly, fewer required rate and rhythm control, or anticoagulation therapy although there was no significant difference in presence of AF at discharge [8].
Cimochowski et al. administered T3 as part of a complex combination of metabolic and mechanical support strategies in patients with severe LV dysfunction [9]. Inotrope requirement, operative mortality, stroke and renal failure were significantly lower in their intervention group although it is clearly impossible to separate T3-effects from other interventions.
Other studies have failed to demonstrate improvements in cardiac output let alone other outcome markers. Guden et al. found no significant differences in post-CPB haemodynamic parameters, dysrhythmia incidence, need for inotropic support, ITU stay and morbidity or mortality in patients receiving T3 [5]. Bennett-Guerrero et al. could demonstrate no beneficial effects of T3 on perioperative haemodynamics compared to Dopamine or placebo in patients at high risk of requiring post-CPB inotrope support [6]. Requirement for pacing in the first 6 h was significantly greater in the T3 and placebo patients but requirement for IABP or inotropes between groups was not significant. There was no difference in time to extubation, time in ITU or to hospital discharge, or other morbidity and mortality between groups [6]. Finally, Teiger et al. were unable to demonstrate significant differences in haemodynamic parameters in a small group given T3 at cross-clamp removal [10].
A number of different doses of T3 or Thyroxine are described. Whilst some authors justify their dose rationale [2,3,6,10,13], others do not [4,5,7,12,14] and it may well be that the optimal dosing regime has not been described. It may also be noteworthy that most studies have been performed in patients with LV impairment [2–4,6,8–14]. One study has reported sex-dependant haemodynamic responses to T3 although outcome measurements were similar [7].
T3 has also been described as rescue therapy in various case series involving high risk cases undergoing cardiac surgery. In 1989 Novitzky et al. gave T3 to 10 patients difficult to wean from CPB and demonstrated significant improvements in cardiac function with decreased IABP or inotrope support [11]. The same author subsequently reported another 68 cases given various T3 doses with similar decreases in mortality compared to predicted not only in their overall group but also in a subset of 12 patients remaining ‘unexpectedly’ CPB-dependant [12]. Malik et al. successfully bridged 9 out of 10 patients with severe cardiogenic shock to LVAD or heart transplantation using IV Thyroxine [13]. Finally, Carrel et al. reported various T3 regimes in post-CPB, brain dead or pre-transplant patients showing apparent improvements in cardiac function [14]. However, their inhomogeneous series lacked consistent management protocols/uniformity of dosage regimes and their data were not subjected to statistical analysis.
7. Clinical bottom line
Thyroxine levels decrease significantly during Cardiopulmonary bypass. However, there is conflicting evidence that prophylactic perioperative thyroxine/triiodothyronine is a useful adjunct in adult patients undergoing cardiac surgery. Whilst some papers report improved haemodynamic parameters in the immediate post-bypass period, there is no standardised dose or evidence that its use decreases postoperative morbidity, mortality or length of stay in the routine patient. It may, however, still be useful as rescue therapy in weaning some high risk cases from CPB or bridging them to LVAD or transplant.
References
Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact CardioVasc Thorac Surg 2003; 2:405–409.
Sirlak M, Yazicioglu L, Inan MB, Eryilmaz S, Tasoz R, Aral A, Ozyurda U. Oral thyroid hormone pretreatment in left ventricular dysfunction. Eur J Cardiothorac Surg 2004; 26:720–725.
Novitzky D, Cooper DK, Barton CI, Greer A, Chaffin J, Grim J, Zuhdi N. Triiodothyronine as an inotropic agent after open heart surgery. J Thorac Cardiovasc Surg 1989; 98:972–977.
Klemperer JD, Klein I, Gomez M, Helm RE, Ojamaa K, Thomas SJ, Isom OW, Krieger K. Thyroid hormone treatment after coronary-artery bypass surgery. New Engl J Med 1995; 333:1522–1527.
Guden M, Akpinar B, Saggbas E, Sanisoglu I, Cakali E, Bayindir O. Effects of intravenous triiodothyronine during coronary artery bypass surgery. Asian Cardiovasc Thorac Ann 2002; 10:219–222.
Bennett-Guerrero E, Jimenez JL, White WD, D'Amico EB, Baldwin BI, Schwinn DA. Cardiovascular effects of intravenous triiodothyronine in patients undergoing coronary artery bypass graft surgery. A randomised, double-blind, placebo-controlled trial. Duke T3 study group. J Am Med Assoc 1996; 275:687–692.
Mullis-Jansson SL, Argenziano M, Corwin S, Homma S, Weinberg AD, Williams M, Rose EA, Smith CR. A randomised double-blind study of the effect of triiodothyronine on cardiac function and morbidity after coronary bypass surgery. J Thorac Cardiovasc Surg 1999; 117:1128–1134.
Klemperer JD, Klein IL, Ojamaa K, Helm RE, Gomez M, Isom OW, Krieger KH. Triiodothyronine therapy lowers the incidence of a trial fibrillation after cardiac operations. Ann Thorac Surg 1996; 61:1323–1327.
Cimochowski GE, Harostock MD, Foldes PJ. Minimal operative mortality in patients undergoing coronary artery bypass with significant left ventricular dysfunction by maximisation of metabolic and mechanical support. J Thorac Cardiovasc Surg 1997; 113:655–664.
Teiger E, Menasche P, Mansier P, Chevalier B, Lajeunie E, Bloch G, Piwnica A. Triiodothyronine therapy in open-heart surgery: from hope to disappointment. Eur Heart J 1993; 14:629–633.
Novitzky D, Cooper DKC, Swanepoel A. Inotropic effect of triiodothyronine (T3) in low cardiac output following cardioplegic arrest and cardiopulmonary bypass: an initial experience in patients undergoing open heart surgery. Eur J Cardiothorac Surg 1989; 3:140–145.
Novitzky D, Fontanet H, Snyder M, Coblio N, Smith D, Parsonnet V. Impact of triiodothyronine on the survival of high-risk patients undergoing open heart surgery. Cardiology 1996; 87:509–515.
Malik FS, Mehra MR, Uber PA, Park MH, Scott RL. Van Meter CH. Intravenous thyroid hormone supplementation in heart failure with cardiogenic shock. J Cardiac Failure 1999; 5:31–37.
Carrel T, Eckstein F, Englberger L, Mury R, Mohacsi P. Thyronin treatment in adult and pediatric heart surgery: clinical experience and review of the literature. Eur J Heart Failure 2002; 4:577–582.(Andrew Ronald, Joel Dunni)
b Department of Cardiothoracic Surgery, James Cook University Hospital, Middlesbrough, UK
Abstract
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether the use of prophylactic perioperative thyroxine therapy during cardiopulmonary bypass in the euthyroid adult patient undergoing routine cardiac surgery can result in an improved cardiac output leading to better clinical outcomes. Altogether 86 papers were identified on Medline and 113 on Embase using the reported search. A further paper was identified by hand-searching of reference lists. Thirteen papers represented the best evidence on the topic. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses were tabulated. We conclude that it is clear that triiodothyronine levels decrease by 50% or more during cardiopulmonary bypass. However, there is conflicting evidence that prophylactic perioperative thyroxine/triiodothyronine therapy is a useful inotropic adjunct in adult patients undergoing routine cardiac surgery and whilst some studies report improved haemodynamic parameters in the immediate post-bypass period there is no evidence that its use influences postoperative morbidity, mortality or length of stay in the elective patient. It may, however, have a role as rescue therapy in supporting some high risk cases during weaning from CPB or bridging to LVAD or transplant.
Key Words: Cardiac surgery; Thyroxine; Triiodothyronine; Postoperative outcomes; Review; Evidence based medicine
1. Introduction
A best evidence topic was constructed according to the structured protocol. This protocol is fully described in the ICVTS [1].
2. Clinical scenario
You are anaesthetising a high risk CABG patient. Before coming off bypass, the surgeon requests that you give some thyroxine. You have never heard of this strategy before and thus, while you give the thyroxine, you decide to review the literature to see if there is any evidence to back up this strategy.
3. Three-part question
In [patients undergoing cardiac surgery], is the use of [thyroxine] associated with [improved cardiac output, better recovery or fewer complications].
4. Search strategy
Medline 1966 to November 2005 using OVID interface, EMBASE 1980 to 2005 Week 52.
[exp Cardiopulmonary Bypass OR CABG.mp. OR exp Thoracic Surgery OR exp Cardiac surgical procedures OR Coronary art$ bypass.mp. OR Cardiopulmonary bypass.mp. OR exp Cardiovascular Surgical Procedures/OR exp Thoracic Surgical Procedures/OR exp Coronary Artery Bypass/OR cardiac transplantation.mp. OR exp Heart Transplantation/] AND [exp Thyroxine/OR Thyroxine.mp. OR exp Triiodothyronine/OR triiodothyronine.mp. OR thyronine.mp. OR exp Thyronines/] AND [exp Cardiac Output/ph, de, su, th OR exp Hemodynamic Processes/OR haemodynamic processes.mp. OR postoperative care.mp. OR exp Postoperative Care/OR exp Anesthesia Recovery Period/OR exp "Recovery of Function"/OR exp Intraoperative Complications/OR exp Postoperative Complications/OR surgical complications.mp. OR Postoperative Complications.mp OR Length of Stay.mp].
5. Search outcome
A total of 86 papers on Medline and 113 on Embase were identified using the reported search. A further relevant paper was identified by hand searching reference lists. Thirteen papers represented the best evidence on the subject and are summarised in Table 1.
6. Results
It is well recognised that decreased thyroxine hormone levels accompanying cardiopulmonary bypass (CPB) can be reversed by thyroxine or triiodothyronine (T3) administration before or during bypass [2–6]. But whilst some studies have shown that this strategy can improve cardiac output there is little evidence that recovery is enhanced and complications decreased.
Several authors have identified some short-term haemodynamic benefits following T3 or thyroxine administration during cardiac surgery. Sirlak et al. gave oral T3 both preoperatively and postoperatively and found significant differences in cardiac index (CI) and systemic vascular resistance (SVR) with decreased inotrope and IABP requirements [2]. But whilst ITU stay was less, there was no significant difference in myocardial ischaemia/infarction rate, atrial fibrillation or death. Novitsky et al. found T3 administration on bypass decreased inotrope and diuretic requirement in patients with ejection fraction (EF) less than 30% although there was no difference in haemodynamic data [3]. Their T3 regime was subsequently modified on the basis of data from this study and repeated in patients with higher ejection fractions. Whilst there was no difference in inotrope or diuretic use in this latter group, cardiac output (CO) was significantly higher and SVR and pulmonary vascular resistance (PVR) lower in their T3-treated group [3]. Mullis–Jansson et al. reported similar improvements in CI in their male cohort following T3 administration at cross-clamp release although both sexes experienced decreased myocardial ischaemia, inotrope dependence/requirement and need for mechanical support [7]. However, their control group was significantly older than their T3-group possibly confounding some of their findings [7]. Finally, Klemperer et al. noted that T3 administration in patients with impaired LV function significantly increased CI and decreased SVR for the first 6 h post-cross clamp removal [4] but found no significant differences in interventions required to support separation from CPB, postoperative inotrope use, duration of postoperative ventilation, ITU or hospital stay, or overall morbidity and mortality. However, whilst this study demonstrated comparable incidences of supraventricular and ventricular dysrhythmias in the first 18 h a subsequent paper by the same authors reported decreased prevalence and incidence of atrial fibrillation (AF) in the T3-treated cohort monitored beyond 24 h [8]. Significantly, fewer required rate and rhythm control, or anticoagulation therapy although there was no significant difference in presence of AF at discharge [8].
Cimochowski et al. administered T3 as part of a complex combination of metabolic and mechanical support strategies in patients with severe LV dysfunction [9]. Inotrope requirement, operative mortality, stroke and renal failure were significantly lower in their intervention group although it is clearly impossible to separate T3-effects from other interventions.
Other studies have failed to demonstrate improvements in cardiac output let alone other outcome markers. Guden et al. found no significant differences in post-CPB haemodynamic parameters, dysrhythmia incidence, need for inotropic support, ITU stay and morbidity or mortality in patients receiving T3 [5]. Bennett-Guerrero et al. could demonstrate no beneficial effects of T3 on perioperative haemodynamics compared to Dopamine or placebo in patients at high risk of requiring post-CPB inotrope support [6]. Requirement for pacing in the first 6 h was significantly greater in the T3 and placebo patients but requirement for IABP or inotropes between groups was not significant. There was no difference in time to extubation, time in ITU or to hospital discharge, or other morbidity and mortality between groups [6]. Finally, Teiger et al. were unable to demonstrate significant differences in haemodynamic parameters in a small group given T3 at cross-clamp removal [10].
A number of different doses of T3 or Thyroxine are described. Whilst some authors justify their dose rationale [2,3,6,10,13], others do not [4,5,7,12,14] and it may well be that the optimal dosing regime has not been described. It may also be noteworthy that most studies have been performed in patients with LV impairment [2–4,6,8–14]. One study has reported sex-dependant haemodynamic responses to T3 although outcome measurements were similar [7].
T3 has also been described as rescue therapy in various case series involving high risk cases undergoing cardiac surgery. In 1989 Novitzky et al. gave T3 to 10 patients difficult to wean from CPB and demonstrated significant improvements in cardiac function with decreased IABP or inotrope support [11]. The same author subsequently reported another 68 cases given various T3 doses with similar decreases in mortality compared to predicted not only in their overall group but also in a subset of 12 patients remaining ‘unexpectedly’ CPB-dependant [12]. Malik et al. successfully bridged 9 out of 10 patients with severe cardiogenic shock to LVAD or heart transplantation using IV Thyroxine [13]. Finally, Carrel et al. reported various T3 regimes in post-CPB, brain dead or pre-transplant patients showing apparent improvements in cardiac function [14]. However, their inhomogeneous series lacked consistent management protocols/uniformity of dosage regimes and their data were not subjected to statistical analysis.
7. Clinical bottom line
Thyroxine levels decrease significantly during Cardiopulmonary bypass. However, there is conflicting evidence that prophylactic perioperative thyroxine/triiodothyronine is a useful adjunct in adult patients undergoing cardiac surgery. Whilst some papers report improved haemodynamic parameters in the immediate post-bypass period, there is no standardised dose or evidence that its use decreases postoperative morbidity, mortality or length of stay in the routine patient. It may, however, still be useful as rescue therapy in weaning some high risk cases from CPB or bridging them to LVAD or transplant.
References
Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact CardioVasc Thorac Surg 2003; 2:405–409.
Sirlak M, Yazicioglu L, Inan MB, Eryilmaz S, Tasoz R, Aral A, Ozyurda U. Oral thyroid hormone pretreatment in left ventricular dysfunction. Eur J Cardiothorac Surg 2004; 26:720–725.
Novitzky D, Cooper DK, Barton CI, Greer A, Chaffin J, Grim J, Zuhdi N. Triiodothyronine as an inotropic agent after open heart surgery. J Thorac Cardiovasc Surg 1989; 98:972–977.
Klemperer JD, Klein I, Gomez M, Helm RE, Ojamaa K, Thomas SJ, Isom OW, Krieger K. Thyroid hormone treatment after coronary-artery bypass surgery. New Engl J Med 1995; 333:1522–1527.
Guden M, Akpinar B, Saggbas E, Sanisoglu I, Cakali E, Bayindir O. Effects of intravenous triiodothyronine during coronary artery bypass surgery. Asian Cardiovasc Thorac Ann 2002; 10:219–222.
Bennett-Guerrero E, Jimenez JL, White WD, D'Amico EB, Baldwin BI, Schwinn DA. Cardiovascular effects of intravenous triiodothyronine in patients undergoing coronary artery bypass graft surgery. A randomised, double-blind, placebo-controlled trial. Duke T3 study group. J Am Med Assoc 1996; 275:687–692.
Mullis-Jansson SL, Argenziano M, Corwin S, Homma S, Weinberg AD, Williams M, Rose EA, Smith CR. A randomised double-blind study of the effect of triiodothyronine on cardiac function and morbidity after coronary bypass surgery. J Thorac Cardiovasc Surg 1999; 117:1128–1134.
Klemperer JD, Klein IL, Ojamaa K, Helm RE, Gomez M, Isom OW, Krieger KH. Triiodothyronine therapy lowers the incidence of a trial fibrillation after cardiac operations. Ann Thorac Surg 1996; 61:1323–1327.
Cimochowski GE, Harostock MD, Foldes PJ. Minimal operative mortality in patients undergoing coronary artery bypass with significant left ventricular dysfunction by maximisation of metabolic and mechanical support. J Thorac Cardiovasc Surg 1997; 113:655–664.
Teiger E, Menasche P, Mansier P, Chevalier B, Lajeunie E, Bloch G, Piwnica A. Triiodothyronine therapy in open-heart surgery: from hope to disappointment. Eur Heart J 1993; 14:629–633.
Novitzky D, Cooper DKC, Swanepoel A. Inotropic effect of triiodothyronine (T3) in low cardiac output following cardioplegic arrest and cardiopulmonary bypass: an initial experience in patients undergoing open heart surgery. Eur J Cardiothorac Surg 1989; 3:140–145.
Novitzky D, Fontanet H, Snyder M, Coblio N, Smith D, Parsonnet V. Impact of triiodothyronine on the survival of high-risk patients undergoing open heart surgery. Cardiology 1996; 87:509–515.
Malik FS, Mehra MR, Uber PA, Park MH, Scott RL. Van Meter CH. Intravenous thyroid hormone supplementation in heart failure with cardiogenic shock. J Cardiac Failure 1999; 5:31–37.
Carrel T, Eckstein F, Englberger L, Mury R, Mohacsi P. Thyronin treatment in adult and pediatric heart surgery: clinical experience and review of the literature. Eur J Heart Failure 2002; 4:577–582.(Andrew Ronald, Joel Dunni)