The Effects of Levosimendan in Cardiac Surgery Patients with Poor Left Ventricular Function.[Report]
Source Anesthesia & Analgesia. 104(4):766-773, April 2007.
Abstract BACKGROUND: Patients with poor left ventricular function often require inotropic drug support immediately after cardiopulmonary bypass. Levosimendan improves cardiac function by a novel mechanism of action compared to currently available drugs. We hypothesized that, in patients with severely compromised ventricular function, the use of levosimendan would be associated with better postoperative cardiac function than with inotropic drugs that increase myocardial oxygen consumption.
METHODS: Thirty patients with a preoperative ejection fraction <=30% scheduled for elective cardiac surgery with cardiopulmonary bypass were randomized to two different inotropic protocols: milrinone 0.5 mg [middle dot] kg-1 [middle dot] min-1 or levosimendan 0.1 mg [middle dot] kg-1 [middle dot] min-1, started immediately after the release of the aortic crossclamp. The treatment was masked to the observers. All patients received dobutamine 5 mg [middle dot] kg-1 [middle dot] min-1.
RESULTS: Stroke volume was similar between groups initially after surgery, but it declined 12 h after surgery in the milrinone group but not in the levosimendan group (P < 0.05 between groups) despite similar filling pressures. Total dose, duration of inotropic drug administration and norepinephrine dose were lower in the levosimendan group than in the milrinone group (P < 0.05). The duration of tracheal intubation was shorter in the former group compared with the milrinone group (P = 0008). Three patients in the milrinone group but none in the levosimendan group died within 30 days of surgery.
CONCLUSION: In cardiac surgery patients with a low preoperative ejection fraction, stroke volume was better maintained with the combination of dobutamine with levosimendan than with the combination of dobutamine with milrinone.
domingo, 15 de julho de 2007
Levosimedan-Artigo
The Effects of Levosimendan in Cardiac Surgery Patients with Poor Left Ventricular Function.[Report]
Source Anesthesia & Analgesia. 104(4):766-773, April 2007.
Abstract BACKGROUND: Patients with poor left ventricular function often require inotropic drug support immediately after cardiopulmonary bypass. Levosimendan improves cardiac function by a novel mechanism of action compared to currently available drugs. We hypothesized that, in patients with severely compromised ventricular function, the use of levosimendan would be associated with better postoperative cardiac function than with inotropic drugs that increase myocardial oxygen consumption.
METHODS: Thirty patients with a preoperative ejection fraction <=30% scheduled for elective cardiac surgery with cardiopulmonary bypass were randomized to two different inotropic protocols: milrinone 0.5 mg [middle dot] kg-1 [middle dot] min-1 or levosimendan 0.1 mg [middle dot] kg-1 [middle dot] min-1, started immediately after the release of the aortic crossclamp. The treatment was masked to the observers. All patients received dobutamine 5 mg [middle dot] kg-1 [middle dot] min-1.
RESULTS: Stroke volume was similar between groups initially after surgery, but it declined 12 h after surgery in the milrinone group but not in the levosimendan group (P < 0.05 between groups) despite similar filling pressures. Total dose, duration of inotropic drug administration and norepinephrine dose were lower in the levosimendan group than in the milrinone group (P < 0.05). The duration of tracheal intubation was shorter in the former group compared with the milrinone group (P = 0008). Three patients in the milrinone group but none in the levosimendan group died within 30 days of surgery.
CONCLUSION: In cardiac surgery patients with a low preoperative ejection fraction, stroke volume was better maintained with the combination of dobutamine with levosimendan than with the combination of dobutamine with milrinone.
Source Anesthesia & Analgesia. 104(4):766-773, April 2007.
Abstract BACKGROUND: Patients with poor left ventricular function often require inotropic drug support immediately after cardiopulmonary bypass. Levosimendan improves cardiac function by a novel mechanism of action compared to currently available drugs. We hypothesized that, in patients with severely compromised ventricular function, the use of levosimendan would be associated with better postoperative cardiac function than with inotropic drugs that increase myocardial oxygen consumption.
METHODS: Thirty patients with a preoperative ejection fraction <=30% scheduled for elective cardiac surgery with cardiopulmonary bypass were randomized to two different inotropic protocols: milrinone 0.5 mg [middle dot] kg-1 [middle dot] min-1 or levosimendan 0.1 mg [middle dot] kg-1 [middle dot] min-1, started immediately after the release of the aortic crossclamp. The treatment was masked to the observers. All patients received dobutamine 5 mg [middle dot] kg-1 [middle dot] min-1.
RESULTS: Stroke volume was similar between groups initially after surgery, but it declined 12 h after surgery in the milrinone group but not in the levosimendan group (P < 0.05 between groups) despite similar filling pressures. Total dose, duration of inotropic drug administration and norepinephrine dose were lower in the levosimendan group than in the milrinone group (P < 0.05). The duration of tracheal intubation was shorter in the former group compared with the milrinone group (P = 0008). Three patients in the milrinone group but none in the levosimendan group died within 30 days of surgery.
CONCLUSION: In cardiac surgery patients with a low preoperative ejection fraction, stroke volume was better maintained with the combination of dobutamine with levosimendan than with the combination of dobutamine with milrinone.
An Economic Analysis of Costs Associated with Development of a Cell Salvage Program.[Miscellaneous Article]
Source Anesthesia & Analgesia. 104(4):869-875, April 2007.
Abstract BACKGROUND: The increasing cost of blood products and associated risks of transfusion have lead to a heightened interest in techniques which reduce or replace allogeneic blood transfusion. The use of cell salvage is being explored in a number of institutions. We present financial information which may be useful to institutions that are considering the addition of a cell salvage service.
METHODS: A review of the cell salvage data from 2328 patients was used to estimate the average cost of a packed red blood cell unit equivalent processed by cell salvage equipment. In addition, an analysis was performed to assess the break-even point of establishing a cell salvage service.
RESULTS: Initial capital outlay to establish a cell salvage service at this institution was $103,551. The annual fixed operating cost was $250,943. The average cost of transfusion of an allogeneic packed red blood cell unit was $200. For an equivalent cell salvage unit, the cost was $89.46. The payback period was 1.9 mo.
CONCLUSION: This analysis suggests that cell salvage can be significantly less expensive than allogeneic blood. The cost of cell salvage in other institutions will vary depending upon case volume, expected levels of blood loss per case, and initial investment costs. A step-by-step formula is provided to assist in the evaluation of a cell salvage service in hospitals of various sizes.
Source Anesthesia & Analgesia. 104(4):869-875, April 2007.
Abstract BACKGROUND: The increasing cost of blood products and associated risks of transfusion have lead to a heightened interest in techniques which reduce or replace allogeneic blood transfusion. The use of cell salvage is being explored in a number of institutions. We present financial information which may be useful to institutions that are considering the addition of a cell salvage service.
METHODS: A review of the cell salvage data from 2328 patients was used to estimate the average cost of a packed red blood cell unit equivalent processed by cell salvage equipment. In addition, an analysis was performed to assess the break-even point of establishing a cell salvage service.
RESULTS: Initial capital outlay to establish a cell salvage service at this institution was $103,551. The annual fixed operating cost was $250,943. The average cost of transfusion of an allogeneic packed red blood cell unit was $200. For an equivalent cell salvage unit, the cost was $89.46. The payback period was 1.9 mo.
CONCLUSION: This analysis suggests that cell salvage can be significantly less expensive than allogeneic blood. The cost of cell salvage in other institutions will vary depending upon case volume, expected levels of blood loss per case, and initial investment costs. A step-by-step formula is provided to assist in the evaluation of a cell salvage service in hospitals of various sizes.
Fator 7 - relato de 2 casos
Coagulopathy After Cardiopulmonary Bypass in Jehovah's Witness Patients: Management of Two Cases Using Fractionated Components and Factor VIIa.[Report]
Source
Anesthesia & Analgesia. 104(4):763-765, April 2007.
Abstract
BACKGROUND: Changes in the Jehovah's Witness (JW) blood refusal policy now give members the personal choice to accept certain processed fractions of blood, such as factor concentrates and cryoprecipitate.METHODS: Two JW patients undergoing complex aortic surgery who developed severe microvascular bleeding after prolonged use of cardiopulmonary bypass were treated with recombinant activated factor VII, cryoprecipitate, and antithrombin concentrate.RESULTS: Cardiopulmonary bypass-induced coagulopathy was successfully treated, allowing chest closure without evidence of thrombotic complications.CONCLUSIONS: Processed blood fractions can be a valuable adjuvant to drugs when treating bleeding in JW patients.
Source
Anesthesia & Analgesia. 104(4):763-765, April 2007.
Abstract
BACKGROUND: Changes in the Jehovah's Witness (JW) blood refusal policy now give members the personal choice to accept certain processed fractions of blood, such as factor concentrates and cryoprecipitate.METHODS: Two JW patients undergoing complex aortic surgery who developed severe microvascular bleeding after prolonged use of cardiopulmonary bypass were treated with recombinant activated factor VII, cryoprecipitate, and antithrombin concentrate.RESULTS: Cardiopulmonary bypass-induced coagulopathy was successfully treated, allowing chest closure without evidence of thrombotic complications.CONCLUSIONS: Processed blood fractions can be a valuable adjuvant to drugs when treating bleeding in JW patients.
Levosimedan-Editorial
Levosimendan in Cardiac Surgery: A
Unique Drug for the Treatment of
Perioperative Left Ventricular
Dysfunction or Just Another Inodilator
Searching for a Clinical Application?
Paul S. Pagel, MD, PhD The myofilament calcium (Ca2) sensitizers are a class of positive inotropic,
vasodilating drugs ("inodilators") that augment myocardial contractility by
increasing the Ca2 sensitivity of the contractile apparatus without altering
intracellular Ca2 concentration (1). Ca2 sensitizers (including levosimendan,
pimobendan, sulmazole, EMD 57033, and MCI-154) have received
considerable attention for the treatment of acute and chronic congestive heart
failure because, unlike 1-adrenoceptor agonists or cardiac phosphodiesterase
(PDE) III inhibitors that stimulate cyclic adenosine monophosphate (cAMP)-
mediated signaling and increase intracellular Ca2 concentration, these drugs
do not adversely affect myocardial oxygen supply-demand relations (2),
produce cardiotoxicity, or predispose to the development of arrhythmias (3).
Levosimendan was developed over a decade ago, and based on a large body
of accumulated experimental and clinical evidence, appears to be the most
promising of these drugs. Levosimendan has already been approved for the
treatment of acute exacerbation of chronic heart failure in several European
countries following European Society of Cardiology guidelines (4,5). The
drug is currently undergoing Phase III clinical trials in the United States
(REVIVE study) to evaluate its utility for the acute or chronic management
of heart failure, and has received "fast-track" status from the Food and
Drug Administration.
The mechanisms by which levosimendan enhances the inotropic state and
produces vasodilation have been extensively studied (1). Briefly, levosimendan
binds to the regulatory protein troponin C (TnC) (6) and stabilizes the
Ca2-bound conformation of TnC, thereby allowing unopposed interaction
between actin and myosin filaments and enhancing the rate and extent of
myocyte contraction (7). A unique feature of levosimendan-TnC binding is its
dependence on intracellular Ca2 concentration that facilitates the interaction
between TnC and Ca2 during systole, while simultaneously allowing Ca2 to
dissociate from the protein during diastole (8). This Ca2-dependence of TnC
binding prevents deleterious abnormalities in relaxation that would otherwise
be expected to occur (9). Preservation of lusitropic function is also facilitated
by the PDE-inhibiting properties of levosimendan that occur at higher doses
of the drug (10). Levosimendan-induced systemic, pulmonary, and coronary
vasodilation occurs as a result of at least three distinct mechanisms. Levosimendan
opens several types of potassium (K) channels (including voltagedependent,
ATP-sensitive, and Ca2-activated forms) in conductance and
resistance vessels, actions that reduce intracellular Ca2 concentration in
vascular smooth muscle (11). Levosimendan induces Ca2 desensitization of
the contractile apparatus in vascular smooth muscle that does not contain TnC
independent of intracellular Ca2 concentration (12). PDE inhibition may also
play a role in vasodilation produced by higher doses of the drug.
Unlike other inotropic drugs, levosimendan may exert important antiischemic
effects by virtue of its actions as a KATP channel opener. Levosimendan
From the Anesthesia Service, the Clement
J. Zablocki Veterans Affairs Medical Center,
Milwaukee, Wisconsin.
Accepted for publication December 7,
2006.
Address correspondence to Paul S. Pagel,
MD, PhD, Clement J. Zablocki Veterans Affairs
Medical Center, Anesthesia Service, 5000
W. National Ave., Milwaukee, WI 53295. Address
e-mail to paul.pagel@med.va.gov.
Copyright © 2007 International Anesthesia
Research Society
DOI: 10.1213/01.ane.0000256864.75206.6d
Vol. 104, No. 4, April 2007 759
activates sarcolemmal (13) and mitochondrial (14) KATP
channels in vitro, and these channels play a critical role in
myocardial protection against reversible and irreversible
ischemic injury (15). Levosimendan reduced myocardial
infarct size in a canine model of ischemia and reperfusion
in vivo, independent of alterations in systemic
hemodynamics or coronary collateral blood flow, and
this beneficial action was abolished by the nonselective
KATP channel antagonist glyburide (16). Levosimendan
enhanced the functional recovery of stunned myocardium
after percutaneous transluminal coronary angioplasty
in patients with acute myocardial ischemia (17)
and was also beneficial for the treatment of cardiogenic
shock resulting from stunning of border zone myocardium
during infarction (18). Brief administration of levosimendan
to patients undergoing coronary artery bypass graft
surgery before cardiopulmonary bypass was associated
with lower postoperative troponin I concentrations (19).
These latter data suggested that levosimendan may be
capable of producing pharmacological preconditioning in
humans, presumably as a consequence of its actions on the
KATP channel.
The clinical efficacy of levosimendan in patients with
heart failure resulting from ischemic heart disease
(20,21), dilated cardiomyopathy (21), and acute myocardial
infarction (22) has been well documented. Levosimendan
causes dose-dependent improvements in
systemic and pulmonary hemodynamics in patients
with heart failure concomitant with a reduction in clinical
symptoms (21); but the myofilament Ca2 sensitizer
does not produce hypotension, exacerbate ongoing ischemia,
or contribute to mortality by increasing the incidence
of arrhythmias (22). In contrast, a major clinical
trial of the PDE III inhibitor, milrinone, in patients
admitted for an acute exacerbation of chronic heart
failure demonstrated that milrinone did not alter inhospital
or 60-day mortality when compared with placebo,
caused more frequent episodes of hypotension
requiring intervention, and increased the incidence of
arrhythmias as compared to placebo (23). When compared
with the -adrenoceptor agonist, dobutamine,
levosimendan also produced more favorable alterations
in hemodynamics and reduced mortality in patients
with low-output heart failure (24) and in those with
cardiogenic shock after percutaneous coronary intervention
(25). The relative superiority of levosimendan when
compared with dobutamine described in these studies
(24,25) may be related to the antiinflammatory and
antiapoptotic effects of the myofilament Ca2 sensitizer
(26). Similar to the findings in the setting of heart failure,
levosimendan has also been shown to increase cardiac
performance concomitant with reductions in pulmonary
capillary occlusion pressure and systemic vascular resistance
in patients with normal (27) and depressed (28,29)
left ventricular (LV) function undergoing cardiac surgery
with or without (30) cardiopulmonary bypass.
In the current issue of Anesthesia & Analgesia, De
Hert et al. (31) provide further evidence that levosimendan
produces beneficial hemodynamic effects in
patients with preoperative LV dysfunction (ejection
fraction 30%) undergoing cardiac surgery who required
inotropic support after cardiopulmonary bypass.
Despite the inherent problems associated with a
strict comparison between drugs of differing pharmacological
action and relative potency, the authors
demonstrate that the combination of IV infusions of
levosimendan (0.1 g kg1 min1) and dobutamine (5
g kg1 min1) produces very similar cardiovascular
effects to those observed with the combination of milrinone
(0.5 g kg1 min1) and dobutamine during the
first 24 h after cardiopulmonary bypass. The data
further suggest that levosimendan-dobutamine may
augment stroke volume index to a greater degree than
milrinone-dobutamine 12 and 24 h after bypass, although
these results may most likely be attributed to
the greater reductions in systemic vascular resistance
observed in patients receiving the combination of
levosimendan and dobutamine. Loading doses of levosimendan
or milrinone were not administered, but
infusions of these drugs were initiated upon removal
of the aortic cross-clamp preceding a prolonged reperfusion
before separation from bypass. Thus, steadystate
plasma concentrations of levosimendan and
milrinone were probably established before bypass
was discontinued. Perhaps of more importance, the
results indicate that the total doses of dobutamine and
norepinephrine (used to treat mean arterial blood
pressure 60 mm Hg) required during the first 48 h
after cardiopulmonary bypass, the total duration of
inotropic drug treatment, the duration of mechanical
circulatory support (intraaortic balloon counterpulsation
was required in four of 15 patients per group),
and time to tracheal extubation were significantly less in
patients receiving levosimendan-dobutamine when compared
with those treated with milrinone-dobutamine. The
beneficial hemodynamic effects of levosimendan have been
shown to persist for at least 24 h after discontinuation of
a continuous infusion as a result of a biologically active
metabolite (OR-1896) (32), and it is likely that the accumulation
and prolonged effect of this metabolite may, at
least partially, account for these dramatic differences
between levosimendan- and milrinone-treated patients.
PDE III inhibitors such as milrinone have been a
mainstay in the pharmacological management of LV
dysfunction after cardiopulmonary bypass for many
years. These drugs are commonly used in combination
with 1-adrenoceptor agonists to provide a synergistic
positive inotropic effect in the presence of bypassinduced
down regulation of the 1-adrenoceptor and
dysfunctional adenylyl cyclase-mediated signal transduction
(33). Because the mechanism of action of levosimendan
is not dependent on this signaling pathway, the
drug may have the distinct advantage of enhancing
myocardial contractility by acting directly at the level of
the contractile apparatus. In addition, levosimendan
may reduce the development of arrhythmias and the
incidence of cardiotoxicity that often occur with other
clinically used inotropic drugs, because increases in
760 Editorial ANESTHESIA & ANALGESIA
intracellular Ca2 concentration do not occur with the
myofilament Ca2 sensitizer at typical therapeutic doses.
KATP channel-mediated antiischemic effects and prolonged
drug action resulting from an active metabolite
also represent potentially important benefits of levosimendan
in patients with LV dysfunction after cardiac
surgery. Thus, the recent findings of De Hert et al. (31)
are certainly promising, and support the work of
previous investigations (28,29). Nevertheless, PDE III
inhibitors and 1-adrenoceptor agonists have a wellestablished
record of clinical efficacy in the treatment of
perioperative LV dysfunction. Given the success of these
drugs in this setting, a fundamental question remains: Is
another positive inotropic drug with vasodilating properties
truly required to successfully treat these patients?
Thus, whether the theoretical advantages of levosimendan
will ultimately translate into improved outcome in
cardiac surgical patients with LV dysfunction is
unknown and will require additional investigation to
define.
Unique Drug for the Treatment of
Perioperative Left Ventricular
Dysfunction or Just Another Inodilator
Searching for a Clinical Application?
Paul S. Pagel, MD, PhD The myofilament calcium (Ca2) sensitizers are a class of positive inotropic,
vasodilating drugs ("inodilators") that augment myocardial contractility by
increasing the Ca2 sensitivity of the contractile apparatus without altering
intracellular Ca2 concentration (1). Ca2 sensitizers (including levosimendan,
pimobendan, sulmazole, EMD 57033, and MCI-154) have received
considerable attention for the treatment of acute and chronic congestive heart
failure because, unlike 1-adrenoceptor agonists or cardiac phosphodiesterase
(PDE) III inhibitors that stimulate cyclic adenosine monophosphate (cAMP)-
mediated signaling and increase intracellular Ca2 concentration, these drugs
do not adversely affect myocardial oxygen supply-demand relations (2),
produce cardiotoxicity, or predispose to the development of arrhythmias (3).
Levosimendan was developed over a decade ago, and based on a large body
of accumulated experimental and clinical evidence, appears to be the most
promising of these drugs. Levosimendan has already been approved for the
treatment of acute exacerbation of chronic heart failure in several European
countries following European Society of Cardiology guidelines (4,5). The
drug is currently undergoing Phase III clinical trials in the United States
(REVIVE study) to evaluate its utility for the acute or chronic management
of heart failure, and has received "fast-track" status from the Food and
Drug Administration.
The mechanisms by which levosimendan enhances the inotropic state and
produces vasodilation have been extensively studied (1). Briefly, levosimendan
binds to the regulatory protein troponin C (TnC) (6) and stabilizes the
Ca2-bound conformation of TnC, thereby allowing unopposed interaction
between actin and myosin filaments and enhancing the rate and extent of
myocyte contraction (7). A unique feature of levosimendan-TnC binding is its
dependence on intracellular Ca2 concentration that facilitates the interaction
between TnC and Ca2 during systole, while simultaneously allowing Ca2 to
dissociate from the protein during diastole (8). This Ca2-dependence of TnC
binding prevents deleterious abnormalities in relaxation that would otherwise
be expected to occur (9). Preservation of lusitropic function is also facilitated
by the PDE-inhibiting properties of levosimendan that occur at higher doses
of the drug (10). Levosimendan-induced systemic, pulmonary, and coronary
vasodilation occurs as a result of at least three distinct mechanisms. Levosimendan
opens several types of potassium (K) channels (including voltagedependent,
ATP-sensitive, and Ca2-activated forms) in conductance and
resistance vessels, actions that reduce intracellular Ca2 concentration in
vascular smooth muscle (11). Levosimendan induces Ca2 desensitization of
the contractile apparatus in vascular smooth muscle that does not contain TnC
independent of intracellular Ca2 concentration (12). PDE inhibition may also
play a role in vasodilation produced by higher doses of the drug.
Unlike other inotropic drugs, levosimendan may exert important antiischemic
effects by virtue of its actions as a KATP channel opener. Levosimendan
From the Anesthesia Service, the Clement
J. Zablocki Veterans Affairs Medical Center,
Milwaukee, Wisconsin.
Accepted for publication December 7,
2006.
Address correspondence to Paul S. Pagel,
MD, PhD, Clement J. Zablocki Veterans Affairs
Medical Center, Anesthesia Service, 5000
W. National Ave., Milwaukee, WI 53295. Address
e-mail to paul.pagel@med.va.gov.
Copyright © 2007 International Anesthesia
Research Society
DOI: 10.1213/01.ane.0000256864.75206.6d
Vol. 104, No. 4, April 2007 759
activates sarcolemmal (13) and mitochondrial (14) KATP
channels in vitro, and these channels play a critical role in
myocardial protection against reversible and irreversible
ischemic injury (15). Levosimendan reduced myocardial
infarct size in a canine model of ischemia and reperfusion
in vivo, independent of alterations in systemic
hemodynamics or coronary collateral blood flow, and
this beneficial action was abolished by the nonselective
KATP channel antagonist glyburide (16). Levosimendan
enhanced the functional recovery of stunned myocardium
after percutaneous transluminal coronary angioplasty
in patients with acute myocardial ischemia (17)
and was also beneficial for the treatment of cardiogenic
shock resulting from stunning of border zone myocardium
during infarction (18). Brief administration of levosimendan
to patients undergoing coronary artery bypass graft
surgery before cardiopulmonary bypass was associated
with lower postoperative troponin I concentrations (19).
These latter data suggested that levosimendan may be
capable of producing pharmacological preconditioning in
humans, presumably as a consequence of its actions on the
KATP channel.
The clinical efficacy of levosimendan in patients with
heart failure resulting from ischemic heart disease
(20,21), dilated cardiomyopathy (21), and acute myocardial
infarction (22) has been well documented. Levosimendan
causes dose-dependent improvements in
systemic and pulmonary hemodynamics in patients
with heart failure concomitant with a reduction in clinical
symptoms (21); but the myofilament Ca2 sensitizer
does not produce hypotension, exacerbate ongoing ischemia,
or contribute to mortality by increasing the incidence
of arrhythmias (22). In contrast, a major clinical
trial of the PDE III inhibitor, milrinone, in patients
admitted for an acute exacerbation of chronic heart
failure demonstrated that milrinone did not alter inhospital
or 60-day mortality when compared with placebo,
caused more frequent episodes of hypotension
requiring intervention, and increased the incidence of
arrhythmias as compared to placebo (23). When compared
with the -adrenoceptor agonist, dobutamine,
levosimendan also produced more favorable alterations
in hemodynamics and reduced mortality in patients
with low-output heart failure (24) and in those with
cardiogenic shock after percutaneous coronary intervention
(25). The relative superiority of levosimendan when
compared with dobutamine described in these studies
(24,25) may be related to the antiinflammatory and
antiapoptotic effects of the myofilament Ca2 sensitizer
(26). Similar to the findings in the setting of heart failure,
levosimendan has also been shown to increase cardiac
performance concomitant with reductions in pulmonary
capillary occlusion pressure and systemic vascular resistance
in patients with normal (27) and depressed (28,29)
left ventricular (LV) function undergoing cardiac surgery
with or without (30) cardiopulmonary bypass.
In the current issue of Anesthesia & Analgesia, De
Hert et al. (31) provide further evidence that levosimendan
produces beneficial hemodynamic effects in
patients with preoperative LV dysfunction (ejection
fraction 30%) undergoing cardiac surgery who required
inotropic support after cardiopulmonary bypass.
Despite the inherent problems associated with a
strict comparison between drugs of differing pharmacological
action and relative potency, the authors
demonstrate that the combination of IV infusions of
levosimendan (0.1 g kg1 min1) and dobutamine (5
g kg1 min1) produces very similar cardiovascular
effects to those observed with the combination of milrinone
(0.5 g kg1 min1) and dobutamine during the
first 24 h after cardiopulmonary bypass. The data
further suggest that levosimendan-dobutamine may
augment stroke volume index to a greater degree than
milrinone-dobutamine 12 and 24 h after bypass, although
these results may most likely be attributed to
the greater reductions in systemic vascular resistance
observed in patients receiving the combination of
levosimendan and dobutamine. Loading doses of levosimendan
or milrinone were not administered, but
infusions of these drugs were initiated upon removal
of the aortic cross-clamp preceding a prolonged reperfusion
before separation from bypass. Thus, steadystate
plasma concentrations of levosimendan and
milrinone were probably established before bypass
was discontinued. Perhaps of more importance, the
results indicate that the total doses of dobutamine and
norepinephrine (used to treat mean arterial blood
pressure 60 mm Hg) required during the first 48 h
after cardiopulmonary bypass, the total duration of
inotropic drug treatment, the duration of mechanical
circulatory support (intraaortic balloon counterpulsation
was required in four of 15 patients per group),
and time to tracheal extubation were significantly less in
patients receiving levosimendan-dobutamine when compared
with those treated with milrinone-dobutamine. The
beneficial hemodynamic effects of levosimendan have been
shown to persist for at least 24 h after discontinuation of
a continuous infusion as a result of a biologically active
metabolite (OR-1896) (32), and it is likely that the accumulation
and prolonged effect of this metabolite may, at
least partially, account for these dramatic differences
between levosimendan- and milrinone-treated patients.
PDE III inhibitors such as milrinone have been a
mainstay in the pharmacological management of LV
dysfunction after cardiopulmonary bypass for many
years. These drugs are commonly used in combination
with 1-adrenoceptor agonists to provide a synergistic
positive inotropic effect in the presence of bypassinduced
down regulation of the 1-adrenoceptor and
dysfunctional adenylyl cyclase-mediated signal transduction
(33). Because the mechanism of action of levosimendan
is not dependent on this signaling pathway, the
drug may have the distinct advantage of enhancing
myocardial contractility by acting directly at the level of
the contractile apparatus. In addition, levosimendan
may reduce the development of arrhythmias and the
incidence of cardiotoxicity that often occur with other
clinically used inotropic drugs, because increases in
760 Editorial ANESTHESIA & ANALGESIA
intracellular Ca2 concentration do not occur with the
myofilament Ca2 sensitizer at typical therapeutic doses.
KATP channel-mediated antiischemic effects and prolonged
drug action resulting from an active metabolite
also represent potentially important benefits of levosimendan
in patients with LV dysfunction after cardiac
surgery. Thus, the recent findings of De Hert et al. (31)
are certainly promising, and support the work of
previous investigations (28,29). Nevertheless, PDE III
inhibitors and 1-adrenoceptor agonists have a wellestablished
record of clinical efficacy in the treatment of
perioperative LV dysfunction. Given the success of these
drugs in this setting, a fundamental question remains: Is
another positive inotropic drug with vasodilating properties
truly required to successfully treat these patients?
Thus, whether the theoretical advantages of levosimendan
will ultimately translate into improved outcome in
cardiac surgical patients with LV dysfunction is
unknown and will require additional investigation to
define.
Coagulopatia em Testemunha de Jeová
Coagulopathy After Cardiopulmonary Bypass in Jehovah’s Witness Patients: Management of and for the Individual Rather than the Religious Institution
[Editorial]
Elder, Lee
Address correspondence and reprint requests to Lee Elder, Associated Jehovah's Witnesses for Reform on Blood, Boise, ID. Address e-mail to leeelder@ajwrb.org.
Jehovah's Witnesses read with interest the case study by Sniecinski et al. (1) concerning advances in treating patients who refuse certain products made from blood. Some Jehovah's Witnesses fit this profile. Accordingly, we are grateful to medical science for advances facilitating safe perioperative care for patients with this preference.
Sniecinski et al. (1) report the cases of two Jehovah's Witness patients, both of whom accepted transfusions from the donated and stored blood supply. This transfusion of products made from donor blood naturally leads one to question claims, made by some Jehovah's Witnesses, of abstaining from donor blood. This difficulty is amplified when reading power of attorney documents published by the Watchtower stating that Jehovah's Witnesses have the option of accepting literally everything from a given unit of donated blood so long as it is sufficiently fractionated beforehand. Understandably, health care providers are left wondering how a person can lay claim to abstaining from blood as an underlying tenet of faith and yet at the same time declare a preference to accept literally anything and everything from donated blood so long as it has been sufficiently fractionated. An added distraction for physicians trying to understand the Jehovah's Witness patient is the Watchtower organization's marketing of itself as representing Jehovah's Witnesses when it comes to medical use of blood.
In the report by Sniecinski et al. (1) it is important to point out the distinction between treating Jehovah's Witnesses as individuals rather than as part of a population within a religious institution that has strict proclamations on treatment options. In their presentation, Sniecinski et al. (1) treat official Watchtower teaching as though it represents the conviction of all individuals within the Jehovah's Witness population. In fact, the Watchtower organization no more represents the entire population of Jehovah's Witnesses in respect to blood than the Roman Catholic Church represents the entire population of Roman Catholics in relation to birth control techniques. A difference between these two religious institutions is that one interjects itself as representing an entire population with respect to a specific teaching while the other makes no claim that its position reflects the convictions of its members. Despite Watchtower's religious teaching, physicians experience many Jehovah's Witness patients willing to conscientiously accept transfusion of any donated blood product (including whole blood, red cells, white cells, platelets, or plasma) so long as the choice is kept confidential. This is based on a conscientious conviction that the choice is consistent with biblical imperatives. Furthermore, these individuals desire autonomy rather than having the Watchtower organization deciding for them what they can and cannot accept medically as a matter of conscience.
A little advertised fact is that the entire population of Jehovah's Witnesses has never universally assented to the Watchtower organization's religious position on blood transfusion. From the teaching's inception until today, individual Jehovah's Witnesses have lobbied the Watchtower to allow all uses of donor blood for medical purposes. Again, the point here is that the doctrine issued by the Watchtower organization is representative of its own hierarchy, and not of the entire population of Jehovah's Witnesses.
Members of Associated Jehovah's Witnesses for Reform on Blood applaud efforts such as those depicted by Sniecinski et al. (1) to advance medical practices in an effort to improve medical therapies and outcomes for patients with peculiar religious convictions. However, we also remind medical doctors to treat Jehovah's Witnesses patients as each individual prefers rather than as a religious organization prefers them to be treated. In this respect clinicians should take the necessary measures to ensure that choices are autonomous personal decisions rather than transposing organizational religious ideology as though it represents individual conviction. At a minimum, treating physicians should arrange for a private meeting with patients so they have an opportunity to speak for themselves, free from religious pressure and in the absence of family members who are also Jehovah's Witnesses. Again, doctors are looking to confirm an individual's preference regarding blood product transfusion and not the preference of family members or a religious organization. Clinicians should likewise avoid pressuring the patient to act contrary to his or her own convictions.
Testemunha de Jeova-editorial
Optimal Care for Patients Who Are Jehovah’s Witnesses
[Editorial]
Schiller, Harvey Jon MD
Conflict of Interest: Dr. Schiller is an unpaid volunteer staff member of Watchtower.
Address correspondence and reprint requests to H. Jon Schiller, MD, 100 Watchtower Dr., Patterson, NY 12563. Address e-mail to Joschill@jw.org.
The article by Sniecinski et al. (1) on the treatment of two Jehovah's Witnesses with coagulopathy presents a laudable approach toward improved communication with patients who may offer a rather unique medical challenge. Three aspects of this paper merit comment.
First, the paper highlights how far we have come in the past few decades in the treatment of Jehovah's Witnesses. Notice, for example, that the postoperative hematocrit in these two patients were 23% and 20% respectively, and that both patients had “good outcomes.” Actually, this is not unusual in the reports on patients who are Jehovah's Witnesses. Yet, it was not that long ago that some physicians generally applied the “10/30” rule as a transfusion trigger. We have learned much about alternatives for treating anemia and now coagulopathy, as this paper shows.
Second, the authors commendably capture the issue here that the decision on whether to receive these processed blood fractions was up to the two patients. This is not, though, some recent “official” change of position. The decision on blood fractions for Jehovah's Witnesses has long been understood to be up to the individual. For example, in a 1981 position paper in JAMA, Dixon and Smalley (2) reported: “While these verses [Genesis 9:3, 4; Leviticus 17:13, 14; Acts 15:19–21] are not stated in medical terms, Witnesses view them as ruling out transfusion of whole blood, packed RBCs, and plasma, as well as WBC and platelet administration. However, Witnesses' religious understanding does not absolutely prohibit the use of components such as albumin, immune globulins, and hemophiliac preparations; each Witness must decide individually if he can accept these” (2). That is still the basic position of Jehovah's Witnesses.
Third, in their paper reporting two good outcomes, Sniecinski et al. (1) conclude that their use of blood fractions “likely contributed to the good outcomes of these patients.” That may be true, but one can never say for sure. Would the patients have survived and done well had they elected not to take these fractions? Over the years, countless papers across all medical specialties have documented good outcomes for Jehovah Witness patients, even when they seemed contrary to expectations. With Witness patients, as the authors rightly note, each individual decides whether to accept minor blood fractions. That decision may be based partly on the information we physicians provide. We need to take care not to “talk a patient into something.” Both these patients received cryoprecipitate, a product pooled from many patients. Though the safety of such products has improved markedly with viral detection and inactivation methods, review of the literature reveals that there is, and will likely continue to be, some element of hazard (3–6). What if a Witness patient received a blood-borne pathogen or had another severe effect (West Nile, Creutzfeldt-Jakob disease, etc.) from our conscientious care? If we had not carefully explained this possibility, he or she might think it was worse than ironic.
Despite our enlightened medical opinion, we know that, morally and legally, the decision about the risks of any procedure must rest with the patient. The article rightly concludes that the physician should “thoroughly discuss what processed blood fractions are acceptable to each individual in this patient population.”
Occasionally, this may seem frustrating. The physician may find that a particular medical procedure or fraction is acceptable to one Witness patient but not to another. Still, is that not what the patient's faith and conscience call on him to do, to make his own decision? And is not the physician's responsibility to help inform the patient and then to do our best within the boundaries defined by the patient's faith and conscience?
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