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Ann Thorac Surg 2007;83:715-723
© 2007 The Society of Thoracic Surgeons

Reviews

Selecting a Vasopressor Drug for Vasoplegic Shock After Adult Cardiac Surgery: A Systematic Literature Review

Moritoki Egi, MDa, Rinaldo Bellomo, MDa,*, Christoph Langenberg, MDa, Michael Haase, MDa, Anja Haase, B Pharma, Laurie Doolan, MDb, George Matalanis, MDc, Siven Seevenayagam, MDc, Brian Buxton, MDc

a Department of Intensive Care and Medicine, University of Melbourne, Austin Hospital, Heidelberg Victoria, Australia
b Department of Anesthesia, Austin Hospital, Heidelberg Victoria, Australia
c Department of Cardiac Surgery, Austin Hospital, Heidelberg Victoria, Australia

* Address correspondence to Dr Bellomo, Department of Intensive Care, Austin Hospital, 145 Studley Rd, Heidelberg Victoria, 3084 Australia. (Email: rinaldo.bellomo{at}austin.org.au).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
The choice of vasopressors to treat vasodilatory shock after cardiac surgery is a matter of controversy. We have systematically reviewed the literature and found that the data are insufficient to guide choice of agent. However, we found sufficient evidence that when a target blood pressure can not be achieved with a single agent, addition of another is more likely to help achieve the blood pressure target. We also found that there is no evidence that vasopressors induce organ ischemia. Finally, the lack of high quality data indicate that large multicenter trials are needed in this field.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 References
 
Vasodilatory (vasoplegic) shock requiring vasopressor support is a recognized and relatively common complication of cardiopulmonary bypass (CPB) [1]. It is characterized by an adequate or elevated cardiac output, a low mean arterial pressure, and evidence of organ dysfunction, such as oliguria or elevated lactate levels or confusion or coronary ischemia. Such physiologic changes in association with a low blood pressure suggest organ dysfunction secondary to insufficient perfusion pressure in turn secondary to vasodilatation. They lead to the initiation of vasopressor therapy with the aim of restoring vessel tone toward normal and improving the perfusion of vital organs. The underlying mechanisms responsible for the decreased vascular resistance seem related to a systemic inflammatory response to CPB and are only partly understood [2–8]. Several factors are associated with postoperative CPB vasodilatory shock, including chronic heart failure, preoperative use of vasodilators, such as angiotensin-converting enzyme inhibitors and beta-blockers, or postoperative use of amiodarone and phosphodiesterase III inhibitors [9–13].

The syndrome of vasoplegic shock has been reported in approximately 5% to 20% of adult patients after CPB [7]. Such shock is typically of limited severity and may only require low doses of vasopressor support to maintain vital organ perfusion pressure [14]. However, in a smaller percentage of cases, a more severe syndrome develops, which requires high-dose vasopressor therapy [10, 15]. The mortality associated with this condition is considerable [16].

Despite a wide range of available vasopressor agents, no consensus exists on the treatment of hyperdynamic vasodilatory shock postoperative CPB, and there is controversy about the choice of vasopressor to achieve an adequate mean arterial pressure (MAP) [17].

This systematic review of the literature seeks to examine the pharmacological options for vasopressor support in the postoperative CPB patient and to describe and classify the available evidence for the choice of vasopressor drugs after CPB in adults.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 References
 
We performed a systematic literature search (January 1980–July 2006) with preset rules. The literature search was performed with MEDLINE and PubMED using the following key words: cardiac surgery, cardiopulmonary bypass, coronary artery bypass grafting, valve surgery, norepinephrine, vasopressin, phenylephrine, methylene blue, dopamine, vasopressor, alpha adrenergic, vasoactive, low systemic vascular resistance, vasoplegia, shock, ischemia, perfusion, and blood flow.

All articles in question were obtained. The bibliographies of articles identified through this methodology were also studied for articles that might have been missed by the electronic reference library methodology. Non-English language papers, animal studies, pediatric studies, and in vitro studies were not included. Papers were selected and graded for quality of evidence according to the methodology of Cook and colleagues [18] (Tables 1, 2). Go One of authors (ME) performed the literature search, read all the articles, and selected those relevant to the current review.


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  		Table 1. Grading of Levels of Evidence
 

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  		Table 2. Grading of Evidence Statements
 
Particular attention was given to the following issues regarding each agent: (1) the ability of each vasopressor to increase systemic arterial pressure; (2) the effects of each vasopressor on systemic hemodynamics; (3) the effect of each vasopressor on measures of vital organ perfusion and function; (4) the effect of each vasopressor on major clinical outcomes (eg, time spent in the hospital or intensive care unit or need for ventilation or artificial renal support); (5) the effect of each vasopressor on survival; and (6) the presence of any important side effects of each vasopressor.

Data on the use of each drug were examined. Evidence-based recommendations were developed where possible.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
Our literature search identified 786 articles. Of these, 164 articles were relevant to cardiac surgery. Of these 164 articles, only 56 reported clinical studies of vasopressor drugs in cardiac surgery patients. Of these 56 articles, only 37 assessed these agents in the postoperative CPB period. These 37 articles were used for the current systematic review. The results of our literature search are considered by pharmacological groups and agents.

Catecholamines
Natural and synthetic catecholamines have different hemodynamic effects because of their differential ability to stimulate adrenergic receptors. Accordingly we considered each separately.

Norepinephrine
Norepinephrine increases MAP by stimulation of {alpha}1-adrenergic receptors in vascular smooth muscle and ß receptors in the kidney causing angiotensin II release [19].

We found 12 studies [17, 20–30] of which only 7 report on its MAP effect, and all found that norepinephrine increases MAP after CPB [22, 23, 25–27, 29, 30]. This increase is typically associated with no change in heart rate, cardiac index, pulmonary capillary wedge pressure, and central venous pressure, but with a significantly greater increase in left ventricular stroke work index [26].

In one study, norepinephrine infusion induced no change in left internal mammary artery graft flows and significantly increased flow through saphenous vein grafts by 21% (n = 21).

Totaro and Raper conducted a small randomized study to compare norepinephrine and epinephrine in patients requiring vasopressor support for the management of vasodilatory shock after CPB (n = 36) [23]. None of 17 patients allocated to the norepinephrine group had acidosis, hyperlactatemia, or a significant decrease in base excess or pH develop. Norepinephrine was associated with a significantly higher base excess and pH (at 1 hour and 6 to 10 hours after starting the infusion) and a lower cardiac index and mixed venous PO2 (at 1 hour after start the infusion) compared with epinephrine. During the norepinephrine study period, cardiac index and limb blood flow, measured using strain gauge plethysmography, did not change significantly compared with the pre-infusion period. Maillet and colleagues [20] also showed that the postoperative use of norepinephrine did not induce hyperlactatemia after cardiac surgery.

Only three studies assessed the effect of norepinephrine infusion on measures of organ perfusion or function. Dunser and colleagues [21] showed that in 63 patients with vasodilatory shock, norepinephrine infusion was not an independent predictor of ischemic skin lesions. Nygren and colleagues [30] conducted small randomized crossover trials to compare norepinephrine and phenylephrine in 10 patients after uncomplicated coronary artery bypass surgery. Norepinephrine infusion did not impair perfusion of the gastrointestinal mucosa. Both norepinephrine and phenylephrine increased splanchnic oxygen extraction and the mixed venous-hepatic vein oxygen saturation gradient significantly. This increase was more pronounced with phenylephrine. Morimatsu and colleagues [17] showed that norepinephrine infusion in patients with hypotensive vasodilatation after CPB did not increase postoperative serum creatinine concentration.

Phenylephrine
Phenylephrine is an {alpha}1-selective agonist. It activates ß adrenergic receptors only at much higher concentrations [31].

We found only nine studies investigating phenylephrine in postoperative CPB patients [26–28, 30, 32–36]. Six of these investigations described that phenylephrine was effective in increasing MAP [26, 27, 30, 32–36]. As part of one randomized study involving patients who had taken angiotensin-converting enzyme inhibitors, phenylephrine failed to increase MAP in a single individual who then went on to respond to angiotensin II [33]. Two remaining studies did not describe the effect of phenylephrine on MAP [28, 36].

In 1991, DiNardo and colleagues [26] showed that phenylephrine at a dose of 0.87 ± 0.37 µg/kg/min increased MAP by 19 mm Hg (25.3%). These increases are typically accompanied by no changed in heart rate, pulmonary capillary wedge pressure, central venous pressure, and cardiac index [34].

In a small randomized study, phenylephrine infusion to increase MAP by 20% and increased internal mammary artery flow in 100% (20 of 20) of patients who were also receiving an infusion of milrinone (level II). However, phenylephrine decreased flow in 40% of patients (4 of 10) who were also receiving a continuous infusion of glyceryl trinitrate (2 µg/kg/min) [32].

In a recent randomized study, phenylephrine infusion to increase MAP by 20%, increased radial artery graft flow in patients by 40%, compared with an increase of 37% with nicardipine and 48% with nitroglycerin (level II) [35].

A prospective crossover observational study investigated the effect of norepinephrine, phenylephrine, and epinephrine on graft blood flow using an electromagnetic flow probe [26]. Phenylephrine infusion to increase MAP by 20 mm Hg significantly decreased flow in the internal mammary artery graft by 20% and induced no significant change in flow through the saphenous vein grafts.

Only two studies assessed organ function during phenylephrine infusion. In this small randomized study, postoperative creatinine clearance was not significantly different in the phenylephrine group compared with either preoperative creatinine clearance or angiotensin II infusion [33]. A study comparing phenylephrine to norepinephrine is previously described [30].

We found no data relating the use of phenylephrine in postoperative CPB patients to survival.

One study assessed the role of postoperative phenylephrine use in relation to the onset of atrial fibrillation after coronary artery bypass grafting [36]. This retrospective study concluded that vasopressor use (including phenylephrine, dopamine, and dobutamine) was an independent predictor of atrial fibrillation after coronary artery bypass grafting. In the univariate analysis, the incidence of atrial fibrillation was significantly lower in patients with phenylephrine compared with patients with dopamine.

Dopamine
Dopamine is a naturally occurring catecholamine that binds to both {alpha} and ß receptor subgroups with ß effects predominating at low dose and {alpha} effects predominating at high dose [31].

We identified five articles reporting the use of high-dose dopamine (equal or greater than 10 µg/kg/min) in postoperative CPB patients [29, 37–40]. Three described that dopamine increased MAP [29, 39, 40]. Two did not describe its effect on MAP.

Dopamine at a dose of 10 µg/kg/min produced either a 23 mm Hg (35%) [29] or a 15 mm Hg (19%) [40] increase MAP compared with the control period.

Only one controlled observational study assessed the hemodynamic changes induced by high-dose dopamine (8 patients had 10 µg/kg/min, 2 patients had 20 µg/kg/min) compared with dobutamine at the same dose [37]. Changing from dobutamine to the same dose of dopamine produced no significant change of MAP. However, dopamine use decreased heart rate and cardiac index and significantly increased pulmonary capillary wedge pressure.

Sato and colleagues [39] have shown that dopamine at a dose of 16 to 20 µg/kg/min produced an average of 9 mm Hg (13.3%) increase in systolic blood pressure compared with the control period. This increase was accompanied by a significant increase in heart rate, pulmonary capillary wedge pressure, and cardiac index. In this study, renal blood flow was measured by the thermodilution method. Renal blood flow increased by 45% (from 431 to 645 mL/min), and vascular resistance for the renal and systemic circulations was decreased by 23% (from 119 to 92 unit/m2) and 30% (from 27.5 to 19.2 units/mm2), respectively.

We were unable to find further data relating to the effect of dopamine on major clinical outcomes or survival in postoperative CPB patients.

Angiotensin II
Angiotensin II is an octapeptide with physiologic effects on vascular tone, renal function, and cardiac function [41]. We identified only one article relating to the use of angiotensin II in postoperative CPB patients [33]. In this small randomized study (level 2), angiotensin II increased MAP and maintained systemic vascular resistance in patients taking angiotensin-converting enzyme inhibitors preoperatively. One patient, in whom phenylephrine did not increase MAP, responded to angiotensin II infusion. Postoperative creatinine clearance was not significantly different in the angiotensin II group compared with preoperative creatinine clearance [33]. There are no data on the effect of angiotensin II on major clinical outcomes or survival.

Methylene Blue
Methylene blue inhibits nitric oxide synthase and guanylyl cyclase and can prevent nitric oxide-mediated vasodilation [42]. We identified three articles reporting its use in postoperative CPB patients [43–45].

The first is a four-center open label placebo-controlled randomized study (level 2) of methylene blue (1.5 mg/kg over 1 hour) in patients with vasoplegic syndrome postoperative CPB. This syndrome was defined as a MAP < 50 mm Hg, a central venous pressure < 5 mm Hg, and pulmonary capillary wedge pressure < 10 mm Hg, a cardiac index ≥ 2.5 L min-1 m-2, and a vasopressor drug requirement (n = 56) [43]. In the presence of these criteria, patients receiving an average of 0.7 µg/kg/min of norepinephrine were randomized to either methylene blue or a placebo. At the time of randomization, their MAP was 48 mm Hg, their central venous pressure was 3.9 mm Hg, and their pulmonary capillary wedge pressure was 7.9 mm Hg.

In this study, 2 hours after infusion of methylene blue, vasoplegia completely resolved in all patients (28 patients) compared with none in the control group. No data were reported about changes in hemodynamics. Furthermore, the methylene blue group patients had a significantly lower mortality and incidence of renal failure, respiratory failure, neuropathy, arrhythmias, sepsis, and multiorgan dysfunction.

Leyh and colleagues [44] conducted a prospective observational study to test the effect of methylene blue (administration, 2 mg/kg over 20 minutes) in 54 patients with norepinephrine-refractory vasoplegia (MAP < 60 mm Hg, cardiac output > 4.0 L/min, systemic vascular resistance < 600 dyne/sec/cm-5 during intravenous norepinephrine infusion at ≥ 0.5 mcg/kg/min). In these patients, central venous pressure was a mean of 14 mm Hg before intervention and cardiac output was 7.6 L/min. One hour after administration of methylene blue, MAP increased (from 68 mm Hg to 72 mm Hg) and the norepinephrine dose decreased (from 0.5 to 0.35 mcg/kg/min). After 6 hours, MAP was 71 mm Hg and the norepinephrine requirement was 0.2 µg/kg/min. These changes were accompanied by a significant decrease in cardiac output (from 7.6 L/min to 6.5 L/min). The serum creatine level did not change significantly within 48 hours after administration of methylene blue compared with the control period.

Recently, Ozal and colleagues [45] conducted a prospective randomized study to test the effect of the prophylactic methylene blue (2 mg/kg over 30 minutes) 1 hour before surgery in patients with pre-defined risks for vasoplegic shock. The two groups (n = 50 in each) showed a significant difference in the incidence of vasoplegic shock (0% in methylene blue patients vs 26% in controls; p < 0.0001) and intensive care unit stay (1.2 days in MB patients vs 2.1 days in controls; p < 0.0001).

Arginine Vasopressin
Vasopressin is a vasopressin receptor agonist. Its principal function is to enhance conservation of water by increasing the permeability of collecting ducts to water (V2 receptors). Vasopressin is also a potent vasoconstrictor and exerts a direct constrictive action on specific smooth muscle receptors (V1 receptors). The V1 receptor activation increases intracellular ionized calcium concentration and contributes to the ultimate response including vasoconstriction, glycogenolysis, platelet aggregation, and adenocorticotropic hormone release [46].

We found 14 studies of vasopressin in postoperative CPB patients [10, 21, 47–58]. Four publications came from a single randomized controlled study. Thirteen reported that vasopressin was effective in increasing MAP [10, 47–58]. One study did not describe the effect of vasopressin on MAP.

We found three randomized controlled studies. In 1977, the first study was made by Argenziano and colleagues [58] was a small (n = 10) single center, randomized, double-blind placebo-controlled study (level 2) of vasopressin (6 IU/hr) in patients undergoing placement of a left ventricular assist device. Vasopressin (6 IU/hr) infusion was begun 5 minutes after CPB and significantly increased MAP by 27 mm Hg (47.3%) and decreased norepinephrine requirement by 16 µg/min (60.0%) without changes in the cardiac index.

In 2003, Morales and colleagues [50], conducted a randomized, double-blind placebo-controlled study (level 2) to assess the effect of vasopressin (1.8 IU/hr) infusion starting 20 minutes before CPB in 27 patients undergoing cardiac surgery while on angiotensin-converting enzyme inhibitors therapy. The 13 patients allocated to vasopressin infusion had significantly lower peak norepinephrine doses (vasopressin at 4.6 ± 2.5 µg/min vs placebo at 7.3 ± 3.5 µg/min; p = 0.03), duration of catecholamine use (vasopressin at 5 ± 6 hours vs placebo at 11 ± 7 hours; p = 0.03) and a number of hypotensive episodes (vasopressin at 1 ± 1 vs placebo at 4 ± 2; p < 0.01).

In 2003, Dunser and colleagues [47–49, 51] conducted a randomized, controlled study (level 2) comparing norepinephrine combined with vasopressin (4 IU/hr) with norepinephrine alone. In this study, 48 patients suffering from vasodilatory shock (MAP < 70 mm Hg, despite adequate fluid resuscitation and a norepinephrine requirement > 0.5 µg/kg/min) were included; the vasopressin plus the norepinephrine group had a significantly higher MAP and cardiac index and lower norepinephrine requirements [51].

Argenziano and colleagues [10, 57] conducted two further studies of vasopressin (6 IU/hr) in patients undergoing placement of a left ventricular assist device with similar findings.

In a separate study by the same group, vasopressin (4–6 IU/hr) infusion to postoperative CPB patients with catecholamine-resistant shock increased MAP by 27 mm Hg (49.1%) and decreased norepinephrine requirement by 0.49 mcg/min/kg (30.2%) with no change in cardiac index and a significant increase in the left ventricular stroke work index [53].

In another study by the same group, vasopressin (4–6 IU/hr) infusion to patients with catecholamine-resistant septic (58.3%) or postoperative CPB shock (41.6%) increased MAP by 24 mm Hg (40.7%) and decreased norepinephrine requirement by 0.47 µg/min/kg (26.1%) and heart rate by 6 beats per minute (5.2%) with no change in stroke volume, but a significant decrease in cardiac index [54].

Morales and colleagues [55] infused vasopressin (6 IU/hr) in patients with postoperative left ventricular assist device vasodilatory shock increased MAP by 17 mm Hg (29%) and decreased norepinephrine requirement by 3.8 µg/min (32.4%) accompanied by no change in cardiac index.

Finally, Masetti and colleagues [52] infused vasopressin (> 6 IU/min) in patients with postoperative CPB shock requiring high-dose norepinephrine (> 30 µg/kg/min) and increased MAP by 30 mm Hg (33.5%). This change was accompanied by a significant decrease in cardiac index.

We found six studies that reported the effects of vasopressin on organ perfusion or function and clinical outcomes.

In a randomized, controlled study, Dunser and colleagues [47, 51], found that vasopressin plus norepinephrine led to significantly higher bilirubin levels, lower platelet counts, lower gut mucosal PaCO2, and a lower lactate compared with controls.

Morales and colleagues [50] found that vasopressin (0.03 IU/min) infusion starting 20 minutes before CPB was associated with a shorter intubation time (vasopressin at 1.0 ± 0.4 days; placebo at 1.4 ± 0.5 days; p = 0.02), and length of intensive care unit stay (vasopressin at 1.2 ± 0.4 days; placebo at 2.1 ± 1.4 days; p = 0.03). In another study, urine output significantly increased after administration of vasopressin (> 6 IU/hr) infusion [52]. In patients with pos left ventricular assist device vasodilatory shock receiving vasopressin (6 IU/hour) infusion, 81.8% of patients with renal insufficiency recovered. Furthermore, 80% of patients with postoperative left ventricular assist device renal insufficiency also recovered [55]. Dunser and colleagues [21] showed that in 63 patients with vasodilatory shock, vasopressin infusion dose did not correlate with ischemic skin lesions.


   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
Vasodilatory (vasoplegic) shock occurs after CPB in approximately 10% of patients. It seems to contribute to morbidity and mortality, length of intensive care unit and hospital stay, and increased cost of care [16]. The widespread use of phosphodiesterase III inhibitors [59–61], angiotensin-converting enzyme inhibitors [62–64], beta blocking agents [65–67], or other potent vasodilators at the time surrounding cardiac surgery may also contribute to the incidence and severity of vasodilatory shock after CPB [9–13]. The incidence of vasoplegic shock has been reported in approximately 5% to 20% of adult patients after CPB [7, 10, 15]. Such shock is typically mild and may only require low doses of vasopressor support to maintain vital organ perfusion pressure [14]. However, Carrel and colleagues [15] have reported that a more severe form of vasoplegic shock, which requires high-dose vasopressor therapy, occurred in 7.5% of postoperative cardiac patients. Furthermore, Gomes and colleagues [16] have also reported that the mortality associated with such severe vasoplegic shock postoperative cardiac surgery was as high as 25%. Thus, this issue is of relevance to cardiac surgeons.

In this setting, vasopressor drugs are often used to maintain an adequate MAP, although there is uncertainty about what constitutes an "adequate" target MAP in such patients [68, 69]. Furthermore, as many drugs are available to increase blood pressure, there is controversy about which agent should be preferably used [17].

To assist clinicians faced with making choices in this field, we conducted a systematic review of the literature searching for data related to the use of vasopressor agents in postoperative CPB patients in the last 27.5 years. The most remarkable finding of this review is the lack of randomized trials focusing on important clinical outcomes in the setting of a relatively common clinical scenario.

The available evidence is often heterogeneous and is unsuitable for meta-analysis. Also, the level of evidence available is low. Of 37 retrieved articles, no level 1 and only 13 level 2 studies were identified [23, 30, 32, 33, 35, 43, 45, 47–51, 58] (Table 3). Furthermore, four of these came from one single study [47–49, 51]. In addition, there were only 14 level 3 and 10 level 4 studies (Table 4).


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  		Table 3. Randomized Studies to Test the Effect of Vasopressor Drugs in Post-Cardiac Surgery Patients (January 1980–July 2006)
 

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  		Table 4. Level 3 and 4 Evidence to Test the Effect of Vasopressor Drugs in Post-Cardiac Surgery Patients (January 1980–July 2006)
 
Nonetheless, after our systematic analysis of the literature, we considered that despite the limitations of the data, some statements can be made, each with an associated level of evidence.

Statement 1: (grade C, level 2)—Norepinephrine, high-dose dopamine, phenylephrine, angiotensin II, methylene blue, and vasopressin, all can increase MAP after CPB.

Statement 2: (grade C, level 2)—There is insufficient evidence to indicate that vasopressor therapy targeted to a given MAP after CPB, using any of the vasopressor drugs available, is physiologically or clinically superior to achieving the same target when using another drug.

Statement 3: (grade C, level 2)—When a target MAP can not be achieved with the high-dose infusion of a single vasopressor agent, the addition of another vasopressor agent, which acts though a different mechanism, is more likely to allow restoration of the MAP to the desired level than further increases in the initial agent.

Statement 4: (grade C, level 2)—There is insufficient evidence that vasopressor drug infusion leads to decreased organ perfusion or function in postoperative CPB patients with vasodilatory shock.

Statement 5: (grade C, level 2)—Norepinephrine infusion postoperative CPB is associated with a significantly lower base deficit, a lower lactate concentration, a higher pH, a lower cardiac index, and a lower mixed venous PO2 compared with epinephrine infusion.

Statement 6: (grade C, level 2)—In patients with vasodilatory shock requiring vasopressor support and with low filling pressures (central venous pressure < 5 mm Hg, pulmonary capillary wedge pressure < 10 mm Hg), methylene blue may reduce the duration of the vasoplegic syndrome and the need for norepinephrine infusion. Methylene blue may also reduce mortality and morbidity in these patients.

Statement 7: (grade C, level 2)—Prophylactic use of methylene blue may reduce postoperative CPB hypotension and vasopressor requirements. Methylene blue in this setting may also be associated with shorter length of stay in the ICU.

Statement 8: (grade C, level 2)—Prophylactic use of vasopressin reduces postoperative CPB hypotension and vasopressor requirements. Vasopressin in this setting may also be associated with shorter intubation time and length of stay in the ICU.

These statements for vasopressor support in vasoplegic shock after adult cardiac surgery may be compared with those published for septic shock [70, 71]. In this setting, it is reported that (1) either norepinephrine or dopamine is the first choice vasopressor agent to correct hypotension in septic shock (grade D), (2) phenylephrine and vasopressin are not recommended as first-line agents in the treatment of septic shock (grade D), and (3) vasopressin may be considered for salvage therapy (grade E). The important difference seen in postoperative cardiac surgery seems to be that some advantages exist for norepinephrine and dopamine over epinephrine and phenylephrine, although there is no high-quality primary evidence to recommend one catecholamine as opposed to another.

Our study had several limitations. First our literature search was performed using MEDLINE and PubMED, not through other important databases, such as the Cochrane systematic reviews database (ie, Embase and Cinahl). The use of more databases may have made the literature review more comprehensive, however our literature review was conducted with preset rules. Furthermore our literature search identified 513 articles from MEDLINE and 492 articles from PubMED. Thus the overlap between MEDLINE and PubMED included only 219 articles from 786.

Second the selection of 37 relevant articles from 786 articles was performed by only one author (ME). The selection by multiple authors by consensus might have minimized the bias. However the selection was done with preset inclusions criteria (ie, human study, English articles, adult patients, related cardiac surgery, and vasopressor), which already acted to minimize selection bias.

Third we used preset key words to search the literature. Thus it is possible that we missed some studies that involved vasopressor agents but did not use our key words. However this seems unlikely.

In conclusion, the evidence available concerning the choice of vasopressor support after CPB is insufficient to determine which agent should be used in preference, because all studies so far have focused on physiologic rather than clinical outcomes. However evidence-based statements can be formulated to help guide clinicians in their selection of drugs and overall approach to the optimization of MAP in patients with postoperative CPB vasoplegia.

Large, multicenter, randomized controlled trials are needed in this group of patients to test whether the choice of vasopressor agent affects clinical outcomes.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

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