Cardiac arrest

* BACKGROUND Although published algorithms and guidelines list epinephrine and vasopressin as either/or choices for treatment of ventricular fibrillation and/or pulseless ventricular tachycardia, little is known about how critical care providers respond to this recommendation.

* OBJECTIVE To assess the use of vasopressin as a first-line drug of choice for ventricular fibrillation and/or pulseless ventricular tachycardia and describe factors that may influence decision making for using vasopressin.

* METHODS A convenience sample from 4 academic medical centers in the United States was recruited to complete a 20-item survey on demographic factors such as year of last Advanced Cardiac Life Support (ACLS) provider course, specialty certification, predominant practice responsibility, and beliefs related to the use of vasopressin for cardiac arrest. Descriptive statistics, Pearson correlation analysis, and logistic regression were used to analyze the data.

* RESULTS A total of 214 critical care providers (80% registered nurses) completed the survey. Year of last ACLS course (r = -0.188, P = .006) was a significant demographic factor, and behavioral beliefs (attitude about using vasopressin) had the strongest relationship (r = 0.687, P < .001) and were the best predictor for intentions to use or recommend the use of vasopressin (beta = 0.589, P < .001).

* CONCLUSIONS Despite the recommendation for vasopressin as an agent equivalent to epinephrine for treatment of ventricular fibrillation and/or pulseless ventricular tachycardia, 63% of respondents used epinephrine as a first-line drug of choice. More research is needed to address the classification system for interpreting the quality of evidence that may influence practice. (American Journal of Critical Care. 2005;14:481-493)

**********

Sudden cardiac death accounts for the majority of deaths related to cardiovascular disease in the United States. (1) Prompt initiation of cardiopulmonary resuscitation with defibrillation for ventricular fibrillation and pulseless ventricular tachycardia is essential for survival. (2) Since the introduction of the standardized course Advanced Cardiac Life Support (ACLS) by the American Heart Association (AHA) in 1974, the ACLS treatment guidelines have become widely accepted as the standard of emergency cardiac care. (2) The ACLS guidelines have been revised during the past 2 decades, adding recommendations that reflect new clinical and research evidence. One of the most recent changes is the recommendation to use vasopressin (class IIb) as an alternative to epinephrine (class indeterminate) if spontaneous circulation is not restored after 3 defibrillating shocks in patients with ventricular fibrillation and/or pulseless ventricular tachycardia. (2) In this article, we address the role of vasopressin during cardiopulmonary resuscitation and report findings among critical care providers about the use of vasopressin as first-line drug therapy for patients with ventricular fibrillation and/or pulseless ventricular tachycardia. We also consider questions about the level of scientific evidence and the quality of evidence, such as the AHA ACLS guidelines, that influence critical care practice.

Literature Review

Historical Background

For 30 years, ACLS guidelines have consistently recommended epinephrine as the only choice for first-line drug therapy if defibrillation is unsuccessful for treatment of ventricular fibrillation and/or pulseless ventricular tachycardia. In 2000 this recommendation changed when the AHA, in conjunction with a variety of other national and international organizations, published a revised comprehensive review and recommendations for cardiopulmonary resuscitation and emergency cardiac care. (2) After more than 500 worldwide experts reviewed and discussed the science on the use of vasopressin in ventricular fibrillation and/or pulseless ventricular tachycardia, a recommendation was made to AHA that vasopressin should be an alternative to epinephrine. The AHA ACLS algorithm for ventricular fibrillation and/or pulseless ventricular tachycardia now states that if initial defibrillation attempts are not successful, administration of epinephrine 1 mg intravenously every 3 to 5 minutes (class indeterminate) or administration of vasopressin as a single 40-unit intravenous dose (class IIb) should be considered. (2)

The level of scientific evidence and the quality of that evidence led the AHA to classify vasopressin as a class IIb drug and epinephrine as a class indeterminate drug in the management of patients with ventricular fibrillation and/or pulseless ventricular tachycardia. In order to ensure an evidence-based approach to resuscitation, a specific template for classifying AHA ACLS recommendations has been in existence since 1992. (2) The recommendations are classified as follows (2):

* class I, always useful with excellent supporting data;

* class IIa, probably useful with good supporting data;

* class IIb, possibly useful with fair supporting data;

* class III, probably harmful; and

* class indeterminate, with inconclusive supporting data.

Pathophysiology of Vasopressin

Endothelium-derived peptides are important regulators of cardiovascular function. First reported by Yanagisawa et al (3) as potent vasoconstrictor peptides, endothelium-derived peptides also have mitogenic and inflammatory properties. (4-6) Endothelin-1, endothelin-2, and endothelin-3 are the 3 isoforms identified; endothelin-1 is studied the most in cardiopulmonary resuscitation. (5) The major site of production of endothelin-1 is endothelial cells; other sites, in order, are the heart, the kidneys, the posterior lobe of the pituitary gland, and the central nervous system. Activation of endothelin-1 leads to an initial release of vasodilator substances, such as nitric oxide and prostaglandins, before vasoconstriction occurs. (7) Vasopressin is a known modulator for the release of endothelin-1 from the vascular endothelium. (5,6)

Secreted from the posterior lobe of the pituitary gland, vasopressin is the most potent natural vasoconstrictor known. (8) Vasopressin release, which is tightly regulated by osmoreceptors in the hypothalamus, is primarily activated by plasma osmolarity. Vasopressin activity is mediated by the G protein receptors [V.sub.1a], [V.sub.1b], and [V.sub.2]. Among the 3 receptors, vasopressin has the most affinity for the [V.sub.2] receptor, which leads to significant renal effects. (8) Other physiological responses that cause the release of vasopressin include gastrointestinal and uterine motility; liver glycogenolysis; platelet aggregation; secretion of adrenocorticotropin, aldosterone, and coagulation factor VIII; pain; nausea; and hypoxia. (8)

Studies in Animals and Humans

The evidence for the 2000 ACLS recommendations that epinephrine and vasopressin be used for management of patients with ventricular fibrillation and/or pulseless ventricular tachycardia comes primarily from studies in animals (9-16); data from studies in humans are limited. (17-19) Epinephrine and/or vasopressin is used during cardiopulmonary resuscitation primarily to increase peripheral vasoconstriction and optimize cardiac output while correction of ventricular fibrillation and/or pulseless ventricular tachycardia is attempted through direct-current countershock or antiarrhythmic agents. (2) In studies in animals, (9-16) increased peripheral vasoconstriction resulted in increased perfusion pressures, increased myocardial and cerebral blood flow, and overall improved outcomes. However, the data for clinical cardiac arrest are less definitive for both epinephrine and vasopressin. (17-19) To date, no trials of epinephrine compared with placebo in humans have been done. Clinical trials of treatment with standard epinephrine and high-dose epinephrine have been completed, (9,12,19) but none of the trials included use of a placebo control.

At the time of the 2000 ACLS guidelines review, in most of the laboratory and clinical studies, treatment with vasopressin during cardiac arrest caused by ventricular fibrillation improved hemodynamic status, myocardial blood flow, and short-term overall outcomes more than did treatment with placebo or epinephrine. Lindner et al (18) were the first to study the use of vasopressin during cardiac arrest attributable to ventricular fibrillation in humans. The 8 patients in that study (18) had no increase in myocardial oxygen demand or lactate production when they were given vasopressin after they did not respond to defibrillation and intravenous epinephrine.

Lindner et al (19) later conducted a double-blinded, randomized study in which they compared vasopressin with epinephrine in patients (n = 40) who had out-of-hospital cardiac arrest due to ventricular fibrillation. In that study, (19) survival outcome at 24 hours was significantly better in patients who received 40 units of vasopressin than in patients who received 1 mg of epinephrine. However, after the release of the 2000 ACLS guidelines, the results of a larger randomized trial (n = 200) by Stiell et al (20) differed from those of Lindner et al. (19) Stiell et al evaluated the outcome of receiving vasopressin or epinephrine for treatment of asystole, pulseless electrical activity, or refractory ventricular fibrillation. They found that survival to 1 hour (P = .66) and survival to discharge from the hospital (P = .67) did not differ between patients given vasopressin and patients given epinephrine.

The other studies reviewed for the 2000 ACLS guidelines were predominately investigations in pigs. (9,10,12,15,16) Compared with treatment with epinephrine, treatment with vasopressin during resuscitation enhanced vasoconstrictive effects during hypoxic and acidotic states associated with cardiac arrest due to ventricular fibrillation. (9,10) In addition, vasopressin was more effective than epinephrine in increasing cerebral perfusion during resuscitation. (12,15,16)

Researchers also think that stress hormones affect hemodynamic status during cardiopulmonary resuscitation in humans. Schultz et al (21) noted that nonsurvivors of cardiopulmonary resuscitation had low levels of adrenocorticotropin and cortisol. However, it was not until after the release of the 2000 ACLS guidelines that Kornberger et al (12) found that vasopressin enhances the release of adrenocorticotropin with subsequent elevation of serum cortisol and improved vascular tone. Other researchers found improved outcomes with repeated doses of vasopressin, (23) elevated endogenous levels of vasopressin, (24) and combination therapy of vasopressin and epinephrine. (25)

Researchers continued to use laboratory studies to evaluate the use of vasopressin during cardiopulmonary resuscitation after the 2000 ACLS guidelines. Krismer et al (26) evaluated the effect of vasopressin on adrenal medullary and cortical blood flow in pigs (n = 19) randomized to receive epinephrine, vasopressin, or a placebo. Medullary and cortical adrenal blood flow pressures were significantly higher when vasopressin and epinephrine were used than when the placebo was used. However, flow pressures were significantly higher with vasopressin than with epinephrine. (26) Stadlbauer et al (27) evaluated neurological effects in pigs (n = 16) randomized to receive a combination of vasopressin and epinephrine, epinephrine, or a placebo. The combination of vasopressin and epinephrine, but not epinephrine alone or placebo alone, resulted in long-term survival with no neurological deficits.

Although some studies (28-32) have indicated that treatment with vasopressin has overall beneficial effects, other studies (33-36) have indicated areas of concern. The main areas of concern are limited clinical studies, (30) reduction in myocardial contractility, (33) increased pulmonary resistance, (34) impairment of microvascular blood flow, (35) and myocardial ischemia during intraoperative hypotensive states. (36) However, Bone et al (32) concluded that the adverse effects revealed in these studies (30,33-36) were probably irrelevant in acute emergency situations such as cardiac arrest due to ventricular fibrillation.

In 2004, Wenzel et al (37) published the results of a clinical trial of the use of vasopressin during cardiopulmonary resuscitation. The concerns about the lack of clinical trials may now start to decrease, especially concern about the role of vasopressin in asystole. During a 3-year period, patients (n = 1186) in 33 different communities in Europe were randomized to receive 2 injections of either 40 units of vasopressin or 1 mg of epinephrine for treatment of out-of-hospital cardiac arrest. The eligibility criteria included the presence of ventricular fibrillation, pulseless electrical activity, or asystole that required cardiopulmonary resuscitation. The results revealed no significant differences in the rates of hospital admission between the groups with either ventricular fibrillation or pulseless electrical activity; however, in patients with asystole, rates of admission were higher for patients treated with vasopressin than for patients treated with epinephrine. (37)

The study by Wenzel et al (37) brought timely needed evidence of the efficacy of vasopressin as the first-line drug intervention for patients with ventricular fibrillation and/or pulseless electrical activity compared with the efficacy of epinephrine. McIntyre (38) thinks that the results of this study (37) are so profound that experts on cardiopulmonary resuscitation and emergency cardiac care should immediately convene and develop interim guidelines, because ACLS revisions are scheduled only every 4 to 5 years. Even though our study reported in this issue of the American Journal of Critical Care was completed before the release of the landmark vasopressin study (37) by Wenzel et al, the question remains, what are critical care providers doing with the current ACLS recommendations for first-line drug intervention in patients with ventricular fibrillation and/or pulseless ventricular tachycardia?

Theoretical Framework for the Study

For more than 2 decades, the theory of reasoned action (TRA) of Ajzen and Fishbein (39) has been used to explain the behavioral beliefs (attitude about a certain behavior), normative beliefs (what others think about the behavior), and control beliefs (how much control to change the behavior) that influence decisions. For our study, beliefs about the use of vasopressin may help explain if this drug will be used or recommended as a first-line drug of choice for ventricular fibrillation and/or pulseless ventricular tachycardia. According to the TRA, intention to perform behavior is predominately determined by both an individual's behavioral beliefs (attitude toward performing the behavior) and normative beliefs (what others think about performing the behavior). (39)

The cornerstone of the theory is that intention is the best predictor of behavior. Likewise, the subjective norms or normative beliefs held by an individual directly influence the intention. The other determinant of behavioral intention is perceived behavioral control, which implies that an individual's motivation is influenced by how difficult the behaviors are perceived to be or how successful the individual can be in performing the behavior. In addition, external factors such as demographics, self-efficacy, and personality traits can influence the dependent criterion (intention to do the behavior or the actual performance of the behavior). (39)

An example of a study with a TRA framework, with close parallels to our study, is an investigation by Ellison. (40) Ellison surveyed 288 nurses about their perceived beliefs on family presence during resuscitative efforts and invasive procedures. The results revealed a significant relationship between behavioral beliefs (attitude) toward family presence and the external factors of educational preparation (r = 0.216, P < .01), type of certification (r = 0.216, P < .01), and area of specialization (r = -0.234, P < .01). (40) Similarly, our results reveal relationships between predictor variables, such as behavioral beliefs (attitude about vasopressin use) and external factors (eg, timing of ACLS course, profession, predominant clinical responsibility), and the dependent criterion (intention to use or recommend vasopressin).

Methods

The purpose of this study was to assess the use of vasopressin as a first-line drug of choice for treatment of patients with ventricular fibrillation and/or pulseless ventricular tachycardia and to describe factors that may influence decision making for using vasopressin among critical care providers in 4 academic settings in the United States.

Sample

After approval was obtained from the appropriate institutional review board, a convenience sample of critical care providers from the 4 academic medical centers was recruited to complete a 20-item survey. Participants for the study were recruited by the investigators affiliated with acute and critical care units in academic medical centers in Washington DC, Dallas, Tex, Fort Worth, Tex, and San Diego, Calif. Settings in which the participants were recruited included cardiovascular, surgical, and medical intensive care units; operating rooms; emergency departments; telemetry units; and step-down medical-surgical units.

Psychometric Analysis of the Instrument

A pilot study (n = 79 critical care providers) was conducted at 2 medical centers, in Washington, DC, and Dallas, Tex, to test the validity and reliability of the instrument. On the basis of the TRA of Ajzen and Fishbein, (39) the survey was developed and underwent content review by 2 nursing faculty colleagues with research experience and 2 healthcare professionals with ACLS instructor experience. Reviewers were asked to use a Likert scale of 1 to 5 to comment on the clarity (1 = not clear to 5 = very clear) and appropriateness (1 = not appropriate to 5 = very appropriate) of each question. Questions with scores of 3 or less on clarity and/or appropriateness were evaluated for possible revision or deletion. In addition, the reviewers addressed the overall scope of the questionnaire by using a Likert scale of 1 to 5 (1 = poorly designed to 5 = well designed).

The appropriateness, meaningfulness, and usefulness of specific inferences made from the pilot test scores were finalized for the validity process. (41) No items were added or reworded, and the mean time for completion of the survey was less than 5 minutes. The coefficient (Cronbach) et was .80 for the 10 items that addressed the TRA framework (n = 79 for the pilot study). However, reliability testing was not completed on individual subscales in the instrument (items addressing behavioral beliefs, normative beliefs, and control beliefs). Power analysis revealed that for an et of .05, a power of 80% and a small effect size of 20%, an approximate sample size of 197 was needed. (41)

Procedure

The surveys were hand distributed on site to targeted critical care providers (registered nurses, advanced practice nurses, physician assistants, clinical pharmacists, and physicians) in the affiliated academic settings by us. Informed consent was addressed in a cover letter attached to each survey. Participants were given the option to complete the survey at that time or to return it within 1 week to a designated area.

Data Analysis

Responses were entered into SPSS Data Editor, version 12.0 (SPSS Inc, Chicago, Ill), and data were analyzed for frequencies, measures of central tendency and dispersion, and reliability statistics. Missing values for continuous variables used in the correlation and regression analysis were replaced with the mean value for that item. A 1-way analysis of variance was used to investigate differences in behavioral beliefs, normative beliefs, and intentions according to selected demographic variables such as type of profession, predominant area of responsibility, ACLS provider status, ACLS instructor status, age, and sex. Pearson product moment correlation was used to study the relationships between the variables, and multiple regression was applied to find the best predictor for the dependent variable (intentions to use vasopressin as first-line drug therapy for patients with ventricular fibrillation and/or pulseless ventricular tachycardia).

Results

Characteristics of the Sample

A total of 214 critical care providers participated in the study (including the 79 participants in the pilot study) by providing complete survey information for data analysis. As summarized in Table 1, the majority of the participants were women (66.8%); the mean age was 38.8 years (SD 9.1, range 21-64). The majority of the participants were white (72.4%) and worked full time (91.6%). A total of 92% of the participants were ACLS providers, and 21.8% were ACLS instructors. in addition, most of the participants (76.2%) had had ACLS training within the previous 2 years. The majority of the participants were registered nurses (79.9%), and 7% identified themselves as advanced practice nurses. Of the advanced practice nurses, 8 were nurse practitioners, 3 were clinical nurse specialists, and 4 were nurse anesthetists (nurse midwives were not targeted for this study). Clinical practice was the predominant area of responsibility for the majority of the participants (90.1%). Slightly less than half of the participants (49.8%) reported certification in their specialty area.

TRA Measures

Internal consistency and reliability of measures for the tool were again computed as in the pilot study, and the Cronbach [alpha] increased slightly to .84. Analysis of the TRA subscales revealed the following Cronbach [alpha]'s: external factors (3 items) .68 and behavioral beliefs (4 items) .87. Values for normative beliefs and control beliefs were not computed because each involved only a single item.

All of the TRA-related questions (Table 2) required a Likert-scale response of 1 to 5. Three external factor items were evaluated for the TRA framework: awareness of AHA ACLS recommendations, frequency of seeing vasopressin used, and frequency of recommending or using vasopressin. Most of the participants (71.5%) were very aware (scores [greater than or equal to] 4) of the 2000 AHA ACLS recommendations for the use of vasopressin as an alternative to epinephrine as first-line drug therapy during ventricular fibrillation and/or pulseless ventricular tachycardia. Only 12.6% of the participants reported that they frequently (scores [greater than or equal to] 4) saw vasopressin used as an alternative to epinephrine as first-line drug therapy during ventricular fibrillation and/or pulseless ventricular tachycardia. Nearly a quarter of the participants (24.3%), reported that they frequently (mean scores [greater than or equal to] 4) used or recommended the use of vasopressin as an alternative to epinephrine as first-line drug therapy during ventricular fibrillation and/or pulseless ventricular tachycardia.

The majority of the participants had positive behavioral beliefs (attitudes toward the use of vasopressin, items 4-7 in Table 2). The percentages of respondents who had scores of 4 or greater were 79.4% for the importance of using vasopressin, 74.3% for the relevance of using vasopressin, 78.1% for the value of using vasopressin, and 72.4% for the receptiveness to use or recommend vasopressin.

Participants rated the normative beliefs (receptiveness of others to use or recommend vasopressin) somewhat lower than they rated their own receptiveness: 8.0% reported that others were not receptive (scores [less than or equal to] 2), 41.6% reported others' receptiveness as neutral (scores = 3), and 49.5% reported that their colleagues were receptive to the use of vasopressin (scores [greater than or equal to] 4). Item 9 addressed the level of control in using or recommending the use of vasopressin, and the results were fairly equal: 32.7% of the respondents had scores of 2 or less, 35.5% had scores of 3, and 31.3% had scores of 4 or greater. On the dependent criterion, intent to use vasopressin within the next 6 months, 63.1% of the participants reported high intentions (scores [greater than or equal to] 4).

Of note, 15% of the participants provided open comments at the end of the survey. The written responses included the following:

Statistical testing for Pearson correlation (Table 3) revealed that all of the independent variables were significantly correlated with intent to use vasopressin. One demographic variables of interest was significantly associated with intentions to use vasopressin. The more recent the ACLS course attendance, the more likely was the intention to use vasopressin (r = -0.188, P=.006). The strongest correlation was with behavioral beliefs (r=0.687, P < .001); next strongest was with control beliefs (r=0.467, P < .001).

The regression results are presented in Table 4. Because external factors of time since last attendance at an ACLS course and age were significantly associated with intention scores, they were used as control variables. Time since last ACLS training was converted into indicator variables; more than 2 years was the control category. Model 1 includes time since ACLS training and age. As can be seen in Table 4, this model is significant (F = 3.495, P = .017) but explains only about 3% of the variance in intentions (adjusted [R.sup.2] = 0.034). External factors (the mean of the scores on awareness, frequency of use, and frequency of seeing vasopressin used) were added next in model 2, again yielding a significant model (F = 9.466, P < .001). Model 2 explains nearly 14% of the variance in intention scores (adjusted [R.sup.2] = 0.137).

Behavioral, normative, and control beliefs are added in model 3 (Table 4). Behavioral beliefs are measured by several items (the mean scores on importance, relevance, valuable, and receptiveness), normative beliefs by the score on perception of colleagues' receptiveness to vasopressin use, and control beliefs by the score on perception of one's control over clinical practice. Model 3, the full model, was significant (F = 37.796, P < .001), with an adjusted squared multiple correlation ([R.sup.2]) of 0.547, meaning 55% of the variance can be explained by these predictors. Time since training, behavioral beliefs, and control beliefs are significantly associated with intentions to use or recommend the use of vasopressin, when age, external factors, and normative beliefs are controlled for. The association between behavioral beliefs (attitude) and intention scores is highly significant ([beta] = 0.755, P < .001). For each unit increase in participants' score on items related to attitude about vasopressin, the intention scores to use or recommend the use of vasopressin increase by 0.755 units ([beta] value or unstandardized regression coefficient).

The Figure is a model that shows the standardized regression coefficients (beta values from model 3 in Table 4). Arrows that go from each independent variable to the dependent variable of intentions indicate the standardized coefficient on that independent variable, controlling for all other variables in the full model (ie, model 3 in Table 4). The use of standardized regression coefficients also allows the ranking of the strength of the various independent variables. As the Figure reveals, behavioral beliefs (self-perceived attitude) has the highest standardized regression coefficient (beta = 0.589, P < .001); next highest is control beliefs (beta = 0.235, P < .001). On the basis of a standardized regression coefficient approximately 2.5 times larger than that for control beliefs, attitude appears to be the best predictor of critical care providers' intentions to use or recommend the use of vasopressin as first-line drug therapy for patients with ventricular fibrillation and/or pulseless ventricular tachycardia.

Discussion

Implications for Practice

In this sample of 214 critical care providers, the majority (71.5%) reported a high level of awareness (scores [greater than or equal to] 4) of the ACLS 2000 recommendation for vasopressin (class IIb) as an alternative to epinephrine (class indeterminate) if spontaneous circulation is not restored after 3 defibrillating shocks in patients with ventricular fibrillation and/or pulseless ventricular tachycardia. However, only 27.7% of the participants reported a high level of frequency (scores [greater than or equal to] 4) of seeing, doing, or recommending the use of vasopressin as an alternative to epinephrine for treatment of patients with ventricular fibrillation and/or pulseless ventricular tachycardia. Lack of awareness has been identified by others (42-46) as a possible deciding factor in following practice guidelines; however, lack of awareness did not appear to be a deciding factor in our study.

As research on the TRA framework suggests, (39) the leading predictor for intentions toward the dependent criterion (in our study, intentions to use vasopressin as an alternative to epinephrine for treatment of ventricular fibrillation and/or pulseless ventricular tachycardia) was behavioral beliefs (attitudes). Unlike other investigators (42-46) of evidenced-based guidelines, we did not specifically target physicians' practices. A small percentage of critical care providers in our study were physicians (9.8%) or professionals such as advanced practice nurses, clinical pharmacists, or physician assistants (9.4%), who typically are in positions to influence practice decisions. This characteristic was recognized as a limitation of the study and may be reflected in the small percentage of participants (31.3%) who thought they had a high level of control to use or recommend using vasopressin as first-line drug therapy for patients with ventricular fibrillation and/or pulseless ventricular tachycardia.

In a time when the accountability of clinical practitioners is of the utmost importance, attempts to influence decision making in order to improve patients' outcomes should be evidence based. When time is of the essence, decisions must be made quickly. The care provider must be able to clearly rationalize why one drug was selected over another drug. Novices in critical care who do not know the long clinical history of the efficacy of epinephrine may make decisions on the basis of which classification is considered best: class IIb or class indeterminate. To the average healthcare provider, are these 2 classifications all that different?

Evidence exists that use of practice guidelines does improve patients' outcomes and that the guidelines should be reviewed and updated as needed. In a systematic review, Grimshaw and Russell (47) noted that at least 1 improvement of care occurred in 93% of the studies reviewed when a change of practice occurred consistent with a guideline recommendation. As indicated in the study by Cline et al, (43) periodic evaluation of adherence to ACLS guidelines provides opportunities to raise awareness and implement changes to improve patients' outcomes. Even though our findings about the subjective norms (what others thought about the use of vasopressin as first-line drug therapy for ventricular fibrillation and/or pulseless ventricular tachycardia) did not have a strong correlation with the dependent criterion (intentions to use vasopressin), almost half of the participants (49.5%) thought that colleagues' impressions of vasopressin influenced decision making.

The purpose of our study was to evaluate current practice in the treatment of patients with ventricular fibrillation and/or pulseless ventricular tachycardia when the ACLS recommendations essentially support either epinephrine or vasopressin as the first-line drug of choice. We think that the recent findings of Wenzel et al (37) will allow a clearer interpretation of a classification recommendation for the use of vasopressin in patients with ventricular fibrillation and/or pulseless ventricular tachycardia. Interpretation of the current classification of vasopressin as a class IIb agent and epinephrine as a class indeterminate agent may be too narrow (ie, care providers may not perceive that much difference between the 2 classifications) to influence decision making. In addition, critical care providers may think that if a drug has a long history of use, a lack of proof of efficacy may not indicate an actual lack of efficacy.

[ILLUSTRATION OMITTED]

Limitations

The limitations of our study provide opportunities for future research. The wording of the demographic items did not adequately identify advanced practice nurses. We were surprised at the actual numbers; more certified registered nurse anesthetists and/or nurse practitioners were observed participating in the study than the data indicate. We think that the classification of registered nurse was selected by many respondents and that the classification of advanced practice nurse (with subsequent selection for nurse practitioner, clinical nurse specialist, certified registered nurse anesthetist) was overlooked. In addition, because 79.9% of the participants were registered nurses, the sample cannot be generalized for a broad representation of critical care providers.

Another limitation was that 2 of the TRA framework components (subscales) were not adequately represented on the measurement tool. Normative beliefs (what others think about vasopressin) and control beliefs (how much control to use or recommend the use of vasopressin) were both addressed with only a single item. The other TRA subscales, behavioral beliefs and external factors, also need additional items to increase reliability measures. (41) In addition, the wording of items for behavioral beliefs needs to be revised. The mean scores for those items were almost the same, and the items were not easily differentiated by using similar words as important, valuable, and relevant.

Even though our results resulted in a significant model, with 55% of the variance explained by the predictors, we recommend adding self-efficacy items for future research. Borenstein et al (48) found that the perceived effectiveness of following clinical practice recommendations increased the likelihood that the recommendations would be adopted for clinical practice. Thus, it would be helpful to know the level of effectiveness critical care providers perceived in using or recommending the use of vasopressin as first-line drug therapy for treatment of patients with ventricular fibrillation and/or pulseless ventricular tachycardia.

Conclusion

This study revealed that among critical care providers at 4 academic medical centers in the United States, epinephrine is the first-line drug of choice for treating patients with ventricular fibrillation and/or pulseless ventricular tachycardia. Because new evidence from Wenzel et al (37) suggests that treatment with vasopressin and treatment with epinephrine result in equivalent outcomes, perhaps critical care providers need updated ACLS recommendations that better reflect current science. In addition, if decision making is to continue to be influenced by evidence-based guidelines, we question if epinephrine should be reclassified at least as a class IIb agent (possibly useful with fair supporting evidence) for first-line drug therapy for patients with ventricular fibrillation and/or pulseless ventricular tachycardia.

Even more important, more emphasis needs to be directed at how best to interpret and actualize scientific evidence at the bedside. Knowledge and awareness of evidence and research are paramount in clinical practice, but the outcomes will never fully be achieved unless caregivers' actions remain consistent with current scientific evidence. Chamberlain (49(p 575)) notes, "There are lessons to be learned from the history of resuscitation. Progress in all disciplines can be hastened if new ideas are welcomed but then evaluated critically, if old practices are not discarded until they can be replaced by others that are demonstrably better."

Commentary by Mary Jo Grap (see shaded boxes).

REFERENCES

(1.) American Heart Association. Heart Disease and Stroke Statistics: 2004 Update. Dallas, Tex: American Heart Association; 2003.

(2.) American Heart Association in Collaboration With the International Liaison Committee on Resuscitation. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiac care. Circulation. 2000;102(suppl I):11-1384.

(3.) Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332:411-415.

(4.) Weissberg PL, Witchell C, Davenport AP, Hesketh TR, Metcalfe JC. The endothelin peptides ET-1, ET-2, ET-3 and sarafotoxin S6b are co-mitogenic with platelet-derived growth factor fur vascular smooth muscle cells. Atherosclerosis. 1990;85:257-262.

(5.) Ortega Mateo A, de Artinano AA. Highlights on endothelins: a review. Pharmacol Res. 1997;36:339-351.

(6.) Balakrishnan SM, Gopalakrishnan V, McNeill JR. Endothelin contributes to the hemodynamic effects of vasopressin in spontaneous hypertension. Eur J Pharmacol. 1997;334:55-60.

(7.) Haynes WG, Webb DJ. Endothelin as a regulator of cardiovascular function in health and disease. J Hypertens. 1998;16:1081-1098.

(8.) Norman AW, Litwack G. Posterior pituitary hormones. In: Hormones. 2nd ed. San Diego, Calif: Academic Press: 1997:109-130.

(9.) Wenzel V, Lindner KH, Prengel AW, et al. Vasopressin improves vital organ blood flow after prolonged cardiac arrest with postcountershock pulseless electrical activity in pigs. Crit Care Med. 1999;27:486-492.

(10.) Wenzel V, Lindner KH, Krismer AC, Miller EA, Voelckel WG, Lingnau W. Repeated administration of vasopressin but not epinephrine maintains coronary perfusion pressure after early and late administration during prolonged cardiopulmonary resuscitation in pigs. Circulation. 1999;99: 1379-1384.

(11.) Wenzel V, Lindner KH, Prengel AW, Lurie KG, Strohmenger HU. Endobronchial vasopressin improves survival after cardiopulmonary resuscitation in pigs. Anesthesiology. 1997;86:1375-1381.

(12.) Prengel AW, Lindner KH, Keller A, Lurie KG. Cardiovascular function during the postresuscitation phase after cardiac arrest in pigs: a comparison of epinephrine versus vasopressin. Crit Care Med. 1996;24:2014-2019.

(13.) Strohmenger HU, Lindner KH, Keller A, Lindner IM, Pfenninger E, Bothner U. Effects of graded doses of vasopressin on median fibrillation frequency in a porcine model of cardiopulmonary resuscitation: results of a prospective, randomized, controlled trial. Crit Care Med. 1996;24:1360-1365.

(14.) Prengel AW, Lindner KH, Keller A. Cerebral oxygenation during cardiopulmonary resuscitation with epinephrine and vasopressin in pigs. Stroke. 1996; 27:1241-1248.

(15.) Lindner KH, Prengel AW, Pfenninger EG, et al. Vasopressin improves vital organ blood flow during closed-chest cardiopulmonary resuscitation in pigs. Circulation. 1995;91:215-221.

(16.) Lindner KH, Brinkmann A, Pfenninger EG, Lurie KG, Goertz A, Lindner IM. Effects of vasopressin on hemodynamic variables, organ blood flow, and acid-base status in a pig model of cardiopulmonary resuscitation. Anesth Analg. 1993;77:427-435.

(17.) Lindner KH, Strohmenger HU, Ensinger H, Hetzel WD, Ahnefeld FW, Georgieff M. Stress hormone response during and after cardiopulmonary resuscitation. Anesthesiology. 1992;77:662-668.

(18.) Lindner KH, Prengel AW, Brinkmann A, Strohmenger HU, Lindner IM, Lurie KG. Vasopressin administration in refractory cardiac arrest. Ann Intern Med. 1996;124:1061-1064.

(19.) Lindner KH, Dirks B, Strohmenger HU, Prengel AW, Lindner IM, Lurie KG. Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation. Lancet. 1997;349:535-537.

(20.) Stiell IG, Hebert PC, Wells GA, et al. Vasopressin versus epinephrine for inhospital cardiac arrest: a randomised controlled trial. Lancet. 2001; 358:105-109.

(21.) Schultz CH, Rivers EP, Feldkamp CS, et al. A characterization of hypothalamic-pituitary-adrenal axis function during and after human cardiac arrest. Crit Care Med. 1993;21:1339-1347.

(22.) Kornberger E, Prengel AW, Krismer A, et al. Vasopressin-mediated adrenocorticotropin release increases plasma cortisol concentrations during cardiopulmonary resuscitation. Crit Care Med. 2000;28:3517-3521.

(23.) Achleitner U, Wenzel V, Strohmenger HU, et al. The effects of repeated doses of vasopressin or epinephrine on ventricular fibrillation in a porcine model of prolonged cardiopulmonary resuscitation. Anesth Analg. 2000; 90:1067-1075.

(24.) Krismer AC, Lindner KH, Wenzel V, et al. The effects of endogenous and exogenous vasopressin during experimental cardiopulmonary resuscitation. Anesth Analg. 2001;92:1499-1504.

(25.) Mayr VD, Wenzel V, Voelckel WG, et al. Developing a vasopressor combination in a pig model of adult asphyxial cardiac arrest. Circulation. 2001; 104:1651-1656.

(26.) Krismer AC, Wenzel V, Voelckel WG, et al. Effects of vasopressin on adrenal gland regional perfusion during experimental cardiopulmonary resuscitation. Resuscitation. 2003;56:223-228.

(27.) Stadlbauer KH, Wagner-Berger HG, Wenzel V, et al. Survival with full neurologic recovery after prolonged cardiopulmonary resuscitation with a combination of vasopressin and epinephrine in pigs. Anesth Analg. 2003;96:1743-1749.

(28.) Wenzel V, Ewy GA, Lindner KH. Vasopressin and endothelin during cardiopulmonary resuscitation. Crit Care Med. 2000;28(11 suppl):N233-N235.

(29.) Cain BS, Shannon-Cann J. Vasopressin in advanced cardiac life support? Crit Care Med. 2001;29:1649.

(30.) Wenzel V, Lindner KH. Arginine vasopressin during cardiopulmonary resuscitation: laboratory evidence, clinical experience and recommendations, and a view to the future. Crit Care Med. 2002;30(4 suppl):S157-S161.

(31.) Chen P. Vasopressin: new uses in critical care. Am J Med Sci. 2002; 324:146-154.

(32.) Bone HG, Westphal M, Van Aken HC. Vasopressin: not only good news. Crit Care Med. 2002;30:2604-2605.

(33.) Leather HA, Segers P, Berends N, Vandermeersch E, Wouters PF. Effects of vasopressin on right ventricular function in an experimental model of acute pulmonary hypertension. Crit Care Med. 2002;30:2548-2552.

(34.) Scharte M, Meyer J, Van Aken H, Bone HG. Hemodynamic effects of terlipressin (a synthetic analog of vasopressin) in healthy and endotoxemic sheep. Crit Care Med. 2001;29:1756-1760.

(35.) Westphal M, Freise H, Kehrel BE, Bone HG, Van Aken H, Sielendamper AW. Arginine vasopressin compromises gut mucosal microcirculation in septic rats. Crit Care Med. 2004;32:194-200.

(36.) Medel J. Boccara G, Van de Steen E, Bertrand M, Godet G, Coriat P. Terlipressin for treating intraoperative hypotension: can it unmask myocardial ischemia? Anesth Analg. 2001;93:53-55.

(37.) Wenzel V, Krismer AC, Arntz HR, et al. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med. 2004;350:105-113.

(38.) McIntyre KM. Vasopressin in asystolic cardiac arrest. N Engl J Med. 2004;350:179-181.

(39.) Ajzen I, Fishbein M. Understanding Attitudes and Predicting Social Change. Englewood Cliffs, N J: Prentice Hall; 1980.

(40.) Ellison S. Nurses' attitudes toward family presence during resuscitative efforts and invasive procedures. J Emerg Nurs. 2003;29:515-521.

(41.) Pedhazur EJ, Schmelkin-Pedhazur L. Measurement, Design, and Analysis: An Integrated Approach. Mahwah, NJ: Lawrence Erlbaum Associates Inc; 1991.

(42.) Greco PJ, Eisenberg JM. Changing physicians' practices. N Engl J Med. 1993;329:1271-1274.

(43.) Cline DM, Welch KJ, Cline LS, Brown CK. Physician compliance with advanced cardiac life support guidelines. Ann Emerg Med. 1995;25:52-57.

(44.) Weingarten S, Stone E, Hayward R, et al. The adoption of preventive care practice guidelines by primary care physicians: do actions match intentions? J Gen Intern Med. 1995; 10:138-144.

(45.) Weingarten S. Practice guidelines and prediction rules should be subject to careful clinical testing. JAMA. 1997;277:1977-1978.

(46.) Cabana MD, Rand CS, Powe NR, et al. Why don't physicians follow clinical practice guidelines? A framework for improvement. JAMA. 1999; 282:1458-1465.

(47.) Grimshaw MJ, Russell IT. Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations. Lancet. 1993;342:1317-1322.

(48.) Borenstein J, Chiou CF, Henning JM, et al. Physician attitudes toward strategies to promote the adoption of medical evidence into clinical practice. Am J Manag Care. 2003;9:225-234.

(49.) Chamberlain D. Never quite there: a tale of resuscitation medicine. Clin Med. 2003;3:573-577.

To purchase electronic or print reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 809-2273 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, reprints@aacn.org.

By Janie Heath, PhD, APRN-BC, ANP, ACNP, Dave Hanson, RN, MSN, CCRN, Rebecca Long, RN, MS, CCRN, CMSRN, and Nancy A. Crowell, MA. From Acute Care Nurse Practitioner and Critical Care Clinical Nurse Specialist Program (JH) and School of Nursing and Health Studies (JH, NAC), Georgetown University, Washington, DC, Cardiovascular Surgery Critical Care, Clarian Health Partners, Methodist Hospital, Indianapolis, Ind (DH), and Veterans Affairs Healthcare System and San Diego State University, School of Nursing, San Diego, Calif (RL).

COPYRIGHT 2005 American Association of Critical-Care Nurses
COPYRIGHT 2005 Gale Group