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American Journal of Critical Care. 2006;15: 580-593
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CE Article

Hemodynamic Changes During Discontinuation of Mechanical Ventilation in Medical Intensive Care Unit Patients

By Susan K. Frazier, RN, PhD, Kathleen S. Stone, RN, PhD, Debra Moser, RN, DNSc, Rebecca Schlanger, RN, MS, CNP, Carolyn Carle, RN, MS, ANP, Lauren Pender, RN, BSN, Jeanne Widener, RN, MS and Heather Brom, RN, BS. From University of Kentucky College of Nursing, Lexington, Ky (SKF, DM) and Ohio State University College of Nursing, Columbus, Ohio (KSS, RS, CC, LP, JW, HB).

Corresponding author: Susan K. Frazier, RN, PhD, Associate Professor, University of Kentucky College of Nursing, 523 CON Bldg, Lexington, KY 40536-0232 (e-mail: skfraz2{at}email.uky.edu).


   Abstract
Top
 Abstract
Review of the Literature
 Purpose
 Methods
 Results
 Discussion
 Limitations
 Conclusions
 References
 
• Background Cardiac dysfunction can prevent successful discontinuation of mechanical ventilation. Critically ill patients may have undetected cardiac disease, and cardiac dysfunction can be produced or exacerbated by underlying pathophysiology.

• Objective To describe and compare hemodynamic function and cardiac rhythm during baseline mechanical ventilation with function and rhythm during a trial of continuous positive airway pressure in medical intensive care patients.

• Methods A convenience sample of 43 patients (53% men; mean age 51.1 years) who required mechanical ventilation were recruited for this pilot study. Cardiac output, stroke volume, arterial blood pressure, heart rate, cardiac rhythm, and plasma catecholamine levels were measured during mechanical ventilation and during a trial of continuous positive airway pressure.

• Results One third of the patients had difficulty discontinuing mechanical ventilation. Successful patients had significantly increased cardiac output and stroke volume without changes in heart rate or arterial pressure during the trial of continuous positive airway pressure. Unsuccessful patients had no significant changes in cardiac output, stroke volume, or heart rate but had a significant increase in mean arterial pressure. The 2 groups of patients also had different patterns in ectopy. Concurrently, catecholamine concentrations decreased in the successful patients and significantly increased in the unsuccessful patients during the trial.

• Conclusions Patterns of cardiac function and plasma catecholamine levels differed between patients who did or did not achieve spontaneous ventilation with a trial of continuous positive airway pressure. Cardiac function must be systematically considered before and during the return to spontaneous ventilation to optimize the likelihood of success.

Notice to CE enrollees:
A closed-book, multiple-choice examination following this article tests your understanding of the following objectives:
  1. Describe the hemodynamic alterations induced by discontinuation of mechanical ventilation.
  2. Recognize the significant influence cardiovascular function may have on the success of ventilator discontinuation.
  3. Understand the patterns of cardiac response during weaning trials.

To read this article and take the CE test online, visit www.ajcconline.org and click "CE Articles in This Issue."

Mechanical ventilation is one of the most common interventions in critical care.1 Unfortunately, as many as one third of patients have difficulty establishing and maintaining adequate spontaneous ventilation after a period of mechanical ventilation.1,2 Discontinuation of mechanical ventilation is commonly called "weaning," though most patients do not require the gradual reduction in ventilatory support implied by this term. Thus, the Collective Task Force of the American College of Chest Physicians, the American Association for Respiratory Care, and the American College of Critical Care Medicine has encouraged the use of "ventilator discontinuation," a more encompassing term, in its published evidence-based guidelines.3 Reasons for failure to establish independent, spontaneous ventilation after a period of ventilator support include oxygenation failure, respiratory muscle dysfunction, psychological dependence, and cardiovascular dysfunction.3,4

Cardiovascular dysfunction may contribute to unsuccessful ventilator discontinuation and promote prolonged dependence on mechanical ventilation. Prolonged dependence is associated with greater risk of mortality,5–7 increased morbidity,6–8 longer length of stay in both the intensive care unit (ICU) and the hospital,5,6,8 and a reduction in functional capacity after discharge from the hospital.9 Cardiovascular dysfunction after extubation may also necessitate reintubation and further ventilator-dependent days. Premature extubation with subsequent reintubation and resumption of mechanical ventilation is also associated with increased morbidity and mortality rates.8,10


   Review of the Literature
Top
 Abstract
 Review of the Literature
Purpose
 Methods
 Results
 Discussion
 Limitations
 Conclusions
 References
 
Numerous investigators in the past 25 years described cardiovascular responses to mechanical ventilation, particularly when used in conjunction with positive end-expiratory pressure. These studies provided evidence that positive-pressure mechanical ventilation with subsequent changes in intrathoracic pressure primarily reduced preload11–14 and left ventricular after-load.15–17 However, later investigations18–21 indicated the importance of baseline ventricular function in the cardiovascular response to mechanical ventilation. Discontinuation of mechanical ventilation also alters cardiovascular state because of changes in intrathoracic pressure.

Cardiovascular instability during discontinuation of mechanical ventilation was first described more than 30 years ago by Beach et al22 in postoperative cardiac surgery patients. Patients who had decreased cardiac output in response to ventilator discontinuation had a concurrent increase in central venous pressure, pulmonary vascular resistance, and systemic vascular resistance. Fifteen years later, Demling et al10 found that 32% of surgical and burn ICU patients (n=22) required reintubation because of unstable hemodynamic status and pulmonary edema. In a similar study,23 nearly one fourth of medical ICU (MICU) patients who did not achieve spontaneous ventilation (n = 18) required reinstitution of mechanical ventilation because of congestive heart failure. Other investigators24,25 have described the need for significantly longer periods of mechanical ventilation in patients with left ventricular dysfunction.

The return to normal mechanics of ventilation commonly increases venous return. Teboul et al26 found a significant increase in right ventricular afterload (pulmonary vascular resistance) during T-piece breathing in patients with chronic obstructive pulmonary disease. Right ventricular dysfunction has been indicated by increased end-diastolic volume during T-piece ventilation in cardiac surgery patients.27 In a sheep model of sepsis, pulmonary vascular resistance was significantly and progressively increased and right ventricular ejection fraction was significantly and progressively reduced with the use of incremental continuous positive airway pressure (CPAP).28 Several investigators26–28 concluded that the global consequences of the cardiovascular response depended on the efficacy of compensatory mechanisms.

In ventilator-dependent patients with chronic cardiopulmonary disease (n=15), left ventricular responses to the discontinuation of mechanical ventilation included the development of acute heart failure concurrently with significant elevations in plasma levels of catecholamines.29 In another study,30 patients with chronic obstructive pulmonary disease without diagnosed coronary artery disease had a significant decrease in left ventricular ejection fraction during T-piece breathing. Clochesy et al23 found that left ventricular function, 24-hour fluid balance, and the number of drugs used to treat heart failure were significantly associated with duration of mechanical ventilation.23 In a more recent survival analysis,27 duration of ventilation was significantly longer in patients with left ventricular dysfunction than in patients without such dysfunction.

Surprisingly, cardiac rhythm has not been examined in any of the studies of ventilator discontinuation in animals or humans.31 Cardiac dysrhythmias may reduce cardiac efficiency and oxygen delivery. Evidence indicates that acute and chronic mechanical cardiac alterations such as those associated with alterations in preload and afterload are arrhythmogenic.32 A considerable degree of evidence links chronic ventricular overload with dysrhythmias.33–36 Ventricular tachyarrhythmias and a greater incidence of sudden cardiac death are more likely in patients with chronic congestive heart failure and associated ventricular dilatation and increased afterload than in patients without these abnormalities.33,34

Although the underlying mechanisms of these dysrhythmias are not clear, current theories suggest that changes in volume and resistance produce mechanical stresses that may influence the function of mechano-sensitive, ion-selective channels in myocytes.37–39 Changes in myocyte cytosolic ion concentration induce electrophysiological alterations that may stimulate dysrhythmias. Ventilator discontinuation may induce mechanical alterations such as acute stretch of the atria and ventricles with increased end-diastolic volume and elevations in afterload. Thus, theoretically, the discontinuation process may generate dysrhythmias.


Cardiovascular instability occurs frequently during discontinuation of mechanical ventilation.

 

In summary, evidence indicates that the institution of mechanical ventilation and the return to spontaneous ventilation induce alterations in intrathoracic pressure that influence cardiovascular function. Despite this evidence, cardiovascular status is not always systematically evaluated before and during discontinuation of mechanical ventilation. Most published criteria1–3,40 require stable hemodynamic status without further definition or description of specific criteria. In addition, many investigators who have suggested that cardiac dysfunction may prevent successful discontinuation of mechanical ventilation studied patients with known cardiac disease. However, many critically ill patients may have undetected cardiac dysfunction. The underlying pathophysiological processes inherent to the critical illness may also induce alterations in cardiac function and affect a patient’s ability to compensate. Thus, many critically ill patients may be unable to respond to hemodynamic changes produced by ventilator discontinuation.


   Purpose
Top
 Abstract
 Review of the Literature
 Purpose
Methods
 Results
 Discussion
 Limitations
 Conclusions
 References
 
The purpose of this investigation was to describe and compare hemodynamic function and cardiac rhythm during baseline mechanical ventilation with function and rhythm during a CPAP ventilator discontinuation trial in a heterogeneous group of MICU patients. The specific aims of the investigation were to


   Methods
Top
 Abstract
 Review of the Literature
 Purpose
 Methods
Results
 Discussion
 Limitations
 Conclusions
 References
 
Design
A descriptive, comparative, repeated-measures design was used in this pilot study. Cardiovascular variables were measured at least 48 hours after the institution of mechanical ventilation and again during the initial CPAP trial. The variables included systolic and diastolic pressure, mean arterial pressure (MAP), cardiac output and stroke volume, heart rate, and cardiac rhythm. Plasma levels of catecholamines were measured at the same time points because of the influence of catecholamines on cardiovascular function.

Sample and Setting
In this pilot investigation, we studied a nonprobability convenience sample (n = 43) of patients after approval by the Biomedical Institutional Review Board of The Ohio State University. The investigation was conducted at The Ohio State University Medical Center, Columbus, Ohio, in the MICU, a 25-bed unit with a mean daily census of 18.4 patients. Nearly all patients in this unit (96%) required mechanical ventilation at some point during their hospitalization, and approximately 30% of patients supported with mechanical ventilation in the unit experienced difficulty in discontinuing ventilator support.

A standardized protocol was used daily to evaluate all patients receiving mechanical ventilation. Each patient’s primary nurse and respiratory therapist used specific parameters: frequency–tidal volume ratio less than 105, positive end-expiratory pressure 5 cm H2O or less, presence of a cough and gag reflex, ratio of PaO2 to fraction of inspired oxygen greater than 200, negative inspiratory force greater than –20 cm H2O, and dopamine infusion 5 µg/kg per minute or less. Once a patient met these established criteria, clinicians initiated a 2-hour trial with CPAP at 5 cm H2O.

All patients admitted to the MICU who required mechanical ventilation and met study inclusion criteria were eligible to participate. Inclusion criteria were mechanical ventilation for a minimum of 48 hours before entry into the study, ventilation administered via an oral or a nasal endotracheal tube, age 18 years or older, and cardiac rhythm originating in the sinus node. Exclusion criteria were administration of continuous vasoactive therapy during ventilator discontinuation, known neurological disorder that might alter ventilatory drive, use of a cardiac pacemaker, recent myocardial infarction (<6 months earlier), recent cerebrovascular accident (<6 months earlier) or diabetes mellitus, use of ß-adrenergic receptor antagonist medications, and terminal status. The criteria of sinus rhythm, no pacemaker, no recent myocardial infarction, no stroke or diabetes, and no use of ß-antagonists were necessary because electrocardiographic (ECG) data were later used to evaluate autonomic tone.

Measures
  Arterial Blood Pressures.   Arterial blood pressure was the value in millimeters of mercury of pressure measured by using a polyvinyl chloride catheter connected to a calibrated transducer (Sorenson, Chicago, Ill). Systolic and diastolic pressures were obtained at the peak and trough, respectively, of the arterial pressure pulse. MAP represented the mean driving pressure of the blood and was calculated by using the following equation: MAP = 2 (diastolic pressure) + systolic pressure/3. The highest and lowest pressures during the data collection periods were used for analysis. Data were collected as the patient received baseline mechanical ventilation (24 hours) and during the CPAP trial (2 hours).

  Cardiac Output.   Cardiac output was the volume of blood ejected by the heart in liters per minute as determined by the differential Fick partial rebreathing technique41 (NICO model 7300, Novametrix Medical Systems, Wallingford, Conn). This method uses a variation of the Fick equation with carbon dioxide used as the indicator substance. The indirect Fick equation is stated as CO = (VCO2/CFormulaCO2) – CaCO2, where CO is the cardiac output, VCO2 is the volumetric carbon dioxide or the clearance of carbon dioxide, CFormulaCO2 is the mixed venous oxygen concentration of carbon dioxide, and CaCO2 is the arterial concentration of carbon dioxide.

Volumetric carbon dioxide is the difference between carbon dioxide content in expired and inspired gas as measured by infrared spectrography. A rebreathing circuit (dead space 150 mL) placed between the endotracheal tube and the ventilator circuit diverted exhaled gas from the endotracheal tube to the rebreathing circuit at regular intervals (about every 3 minutes). The patient rebreathed this gas for about 50 seconds, and elimination of carbon dioxide was reduced during this period. Cardiac output was calculated by determining the difference between elimination of carbon dioxide during normal ventilation and elimination during the rebreathing period. Estimates of intrapulmonary shunt were calculated and were included in the measurement.

Values used for analysis were the mean of measures made during a 1-hour period the morning of baseline data collection and the mean of measures made at 1 hour into the CPAP trial. The baseline period used was chosen to represent a mean morning cardiac output while the patient received mechanical ventilation. Measures were made at the 1-hour point in the CPAP trial because previous research20 indicated that hemodynamic alterations occur within 15 minutes of removal of positive-pressure ventilation and are stabilized within 60 minutes of the change in intrathoracic pressure.

The range of cardiac output measured with this method is 0 to 19.9 L/min. Bias and precision of this measure, compared with cardiac output determined by using a thermodilution method, have been reported as 0.01 ± 0.62 L/min with a correlation coefficient of r = 0.8542 and 0.01 ± 0.69 L/min.43 This technique has been found to be valid and reliable with a variety of patients, including patients after cardiac surgery,42 patients with multiple trauma,43 patients with high and low pulmonary shunt fractions receiving mechanical ventilation,44 and children who require cardiac catheterization.45


Discontinuation of mechanical ventilation causes alterations in intrathoracic pressure that affect cardiac function.

 

  Stroke Volume.   Stroke volume was the volume in milliliters ejected by the heart with each beat as determined by the differential Fick partial rebreathing method.

  Heart Rate.   Heart rate was calculated as the number of R waves each minute obtained from a continuous ECG recording. Values used for analysis were the mean of measures made during a 1-hour period the morning of baseline data collection and the mean of measures made 1 hour into the CPAP trial. These times were chosen to coincide with measurement of cardiac output.

  Cardiac Rhythm.   Cardiac rhythm was determined by evaluation of cardiac electrical events obtained by using a calibrated, frequency-modulated 3-channel ECG monitor (Zymed, Camarillo, Calif) using leads I, II, and V2. Holter tapes were scanned with a scanner (model 363, Delmar AccuPlus, Del Mar Medical, Irvine, Calif) in semiautomatic mode with operator confirmation of all beats. Ectopic beats per hour were calculated from the 24-hour baseline data tape and from the 2-hour CPAP trial time.

  Catecholamines.   Epinephrine and norepinephrine are plasma catecholamines liberated in response to activation of the sympathetic nervous system. Catecholamine concentrations were measured using a Waters 460 Electrochemical Detector (Milford, Mass) with high-pressure liquid chromatography with electrochemical detection and an acid-washed alumina extraction procedure.46 Intra-assay and inter-assay coefficients of variation were less than 8% for both epinephrine and norepinephrine, indicating reproducible and valid measurement.

Procedure
Informed consent was obtained from each patient or the patient’s appropriate surrogate before the patient’s entry into the study. Patients remained in the study until the following occurred: they were weaned and extubated, they requested to be removed from the study, their condition was evaluated as terminal, they experienced a complication that excluded them from participating in the study (eg, myocardial infarction), or they received 28 continuous days of mechanical ventilation without attempts to discontinue ventilation. At the time of admission to the study, demographic data were collected from the patient’s medical record. For those variables measured more than once in a 24-hour period (eg, arterial blood gases), the highest and lowest values in that 24-hour period were recorded. Because of the potential effect of fluid volume status on cardiac function,23,27 fluid volume balance was monitored daily.

At baseline, within 24 hours of entry into the study, blood was obtained for baseline determination of catecholamine levels. These specimens were collected in the early morning via an indwelling vascular access device after a 30-minute period without nursing or medical intervention. Patients were supine with the head of the bed elevated no more than 30° to control factors that influence neurohormones.

Blood was placed in prechilled, polyethylene tubes containing EDTA 1 mg/mL, gently inverted to ensure proper mixing, and immediately placed in ice. Within 20 minutes of sampling, plasma was extracted by centrifuging the tubes in a refrigerated centrifuge (4°C) at 3000g for 10 minutes. The plasma was then drawn off, placed in a polypropylene sample tube, and flash-frozen at –70°C for batch analysis by the Endocrine Laboratory of the Clinical Research Center, The Ohio State University.

After preparation of the skin according to the regimen recommended by the American Heart Association, electrodes were placed in the appropriate configuration, and a 24-hour, 3-lead continuous ECG recording was obtained for baseline cardiac rhythm. Arterial blood pressures were evaluated by using an established arterial cannula connected to a standardized, calibrated pressure transducer. Cardiac output and stroke volume were measured by using the carbon dioxide rebreathing technique described earlier.

All patients were evaluated every morning by MICU clinicians, who used protocol criteria. The study project director also evaluated patients each morning to determine their readiness to discontinue ventilation and to calculate their ongoing fluid balance. Once a patient met the established criteria, study personnel placed the continuous ECG recording device. ECG recordings were started 1 hour before the CPAP trial, obtained continuously throughout the trial period (2 hours) and up to 24 hours after extubation for patients whose initial trial was successful. Blood samples for catecholamine levels were obtained 1 hour after initiation of the CPAP trial. Arterial blood pressures, cardiac output, and stroke volume were also measured at this point.


At baseline, patients who failed the CPAP trial had more ventricular ectopy than did those with a successful trial.

 

Samples for measurement of arterial blood gases were obtained at the end of the 2-hour CPAP trial, and patients with adequate oxygenation and ventilation were extubated. Mechanical ventilation was resumed for patients who experienced hypoxemia, hypercapnia, and/or cardiorespiratory distress. Success was defined as independent spontaneous ventilation for 48 hours after extubation. Mechanical ventilation was resumed for patients who did not tolerate spontaneous, independent ventilation during the CPAP trial, and subsequent trials were also evaluated until discontinuation was successful. This report includes only data from the initial CPAP trial. Data were analyzed by using SPSS for Windows 13.0 (SPSS Inc, Chicago, Ill).

Data Analysis
Descriptive statistics were used to characterize the sample and to describe cardiovascular function during baseline mechanical ventilation and discontinuation of ventilation. Subjects were separated into successful and unsuccessful groups on the basis of the outcome of their CPAP trial, and variables were described and compared. Repeated-measures analysis of variance was used to compare mean values obtained during baseline mechanical ventilation with values obtained during the CPAP trial. Differences were considered significant at an a priori {alpha} level of .05 or less.


   Results
Top
 Abstract
 Review of the Literature
 Purpose
 Methods
 Results
Discussion
 Limitations
 Conclusions
 References
 
Characteristics of the Sample
A total of 43 patients were enrolled in the study (Table 1Go). Slightly more than half (53%) were men. Patients had a mean age of 51.1 years and were hospitalized a mean of 2.5 days before MICU admission and initiation of mechanical ventilation. Nearly half (47%) of the patients were admitted because of pulmonary conditions (eg, acute respiratory distress syndrome, pneumonia, exacerbation of chronic obstructive pulmonary disease). Approximately one fifth (21%) had previously documented heart disease, which included hypertension (n = 4), remote myocardial infarction (>20 years before this admission; n=1), coronary artery disease (n = 2), cor pulmonale (n = 2), and heart failure (n = 1). The mean score on the Acute Physiology and Chronic Health Evaluation II at the time of admission to the study was 25.7, and the mean score on the Glasgow Coma Scale was 9. At the time of the CPAP trial, the mean score on the Acute Physiology and Chronic Health Evaluation II had improved to 14, and the mean score on the Glasgow Coma Scale had increased to 12.


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  		Table 1 Characteristics of the patients (n = 43) at the time of entry into the study

 
Slightly more than one third of the patients (35%) did not achieve independent spontaneous ventilation with the initial CPAP trial and required a mean of 1.5 attempts (range 1–10 trials) before they were successful. Mean duration of mechanical ventilation was 11.7 days. Additional clinical and ventilator variables at baseline and on the day of the CPAP trial are given in Table 2Go.


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  		Table 2 Clinical characteristics of the patients (n = 43) at the time of entry into the study and on the day of trial of continuous positive airway pressure*

 
At entry into the study, patients had a mean positive fluid balance of 653 (SD 1254) mL. At the time patients met the established criteria for the CPAP trial, they had a mean negative fluid balance of –315 (SD 1737) mL. Patients who were successful with their CPAP trial had smaller changes in fluid balance than did patients who were not successful; for the successful group, the change was from 628 (SD 1243) mL at baseline to –292 (SD 1814) mL during CPAP; for the unsuccessful group, the change was from 1104 (SD 1210) mL at baseline to –418 (SD 1479) mL during CPAP.

Arterial blood gases, ratio of PaO2 to fraction of inspired oxygen, frequency–tidal volume ratio, mean airway pressure, peak airway pressure, and airway resistance were also measured at baseline with the patients receiving mechanical ventilation and at the end of the 2-hour CPAP trial to determine differences between the successful and unsuccessful groups (Table 3Go). These variables did not differ significantly between the groups.


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  		Table 3 Comparison of blood gas and selected pulmonary values during trial of continuous positive airway pressure in patients who were successful (n = 28) or unsuccessful (n = 15) in achieving spontaneous ventilation during the trial*

 

Supraventricular ectopic beats during the CPAP trial more than doubled in patients who failed the trial.

 

Hemodynamic Indices
  Arterial Blood Pressure.   Systolic and diastolic pressure and MAP results were evaluated for the highest and lowest values obtained during the data collection periods. For the entire group, none of the pressures at baseline differed significantly from those during the CPAP trial (Table 4Go). When patients were separated into groups on the basis of the outcome of their CPAP trials (successful or unsuccessful), differences between the 2 groups in systolic or diastolic pressure were not significant. However, patients who were unsuccessful had a significant change in MAP, from a mean of 86 (SD 26) mm Hg at baseline to a mean of 110 (SD 18) mm Hg during the trial (P = .008), whereas the successful group had no significant change.


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  		Table 4 Arterial blood pressures at baseline and during continuous positive airway pressure in 43 patients

 
  Cardiac Output.   For the total sample, mean cardiac output was 5.3 (SD 2.9) L/min at baseline during mechanical ventilation (Figure 1Go) and increased significantly to 6.5 (SD 2.9) L/min during the CPAP trial (P = .036). Within the 2 groups, the increase from the baseline value to the CPAP value was significant for the successful group (P = .013) but not for the unsuccessful group.


Figure 1
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  		Figure 1 Cardiac output response to trial of continuous positive airway pressure (CPAP) for all patients (n = 43) and for patients who were successful (n = 28) or unsuccessful (n = 15) in achieving spontaneous ventilation.

 
  Stroke Volume.   For the total sample, mean stroke volume was 52 (SD 36) mL per beat at baseline during mechanical ventilation (Figure 2Go) and increased significantly to 78 (SD 38) mL per beat (P < .001) during the CPAP trial. Within the 2 groups, the increase from the baseline value to the CPAP value was significant (P = .007) for the successful group but not for the unsuccessful group.


Figure 2
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  		Figure 2 Stroke volume response to trial of continuous positive airway pressure (CPAP) for all patients (n = 43) and for patients who were successful (n = 28) or unsuccessful (n = 15) in achieving spontaneous ventilation.

 
  Heart Rate.   For the total sample, mean heart rate was 92 (SD 20) beats/min at baseline during mechanical ventilation and 93 (SD 18) beats/min during the CPAP trial (P = .48). Mean heart rates for the 2 groups were similar at baseline and did not change significantly during the CPAP trial: 95 beats/min at baseline versus 93 beats/min during the trial for the successful group and 97 versus 98 beats/min for the unsuccessful group.

  Cardiac Rhythm.   Baseline electrocardiographic data were evaluated from a 24-hour Holter tape as previously described. CPAP trial data collection began 1 hour before the start of the 2-hour CPAP trial and ended with the end of the trial (extubation or return to mechanical ventilation). All patients were in normal sinus rhythm. A total of 4 patients (3 successful, 1 unsuccessful) experienced excessive ectopy throughout hospitalization; the data on these 4 were excluded from the analysis. Overall, in the 39 patients whose data were analyzed, the number of supraventricular ectopic beats per hour during the CPAP trial was almost double the number at baseline; the number of ventricular ectopic beats per hour decreased by nearly two thirds (Table 5Go). However, patients who were unsuccessful in the CPAP trial tended to have more ventricular ectopy at baseline than did patients in the successful group. Successful patients tended to have a decrease in ventricular ectopic beats during the CPAP trial; the unsuccessful group had no change. During the CPAP trial, the number of supraventricular ectopic beats per hour increased in both groups. The increase was greater for the unsuccessful group; in this group, the number of beats per hour more than doubled.


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  		Table 5 Summary of ventricular and supraventricular ectopy in patients who were or were not successful in achieving spontaneous ventilation during a trial of continuous positive airway pressure*

 
  Catecholamines.   The plasma concentrations of epinephrine and norepinephrine at baseline and during the CPAP trial are given in Table 6Go. For the unsuccessful group, the increase in norepinephrine from the mean baseline value of 4037 (SD 3008) nmol/mL to the CPAP value of 5668 (SD 5343) nmol/mL was significant (P = .02).


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  		Table 6 Plasma catecholamine levels at baseline and during continuous positive airway pressure for patients who were or were not successful in achieving spontaneous ventilation

 

   Discussion
Top
 Abstract
 Review of the Literature
 Purpose
 Methods
 Results
 Discussion
Limitations
 Conclusions
 References
 
The patients in this study received mechanical ventilation for a mean of almost 12 days primarily for pulmonary reasons. Only about one fifth of the sample had previously diagnosed heart disease. Slightly more than one third of the sample had difficulty discontinuing mechanical ventilation. There were striking differences in cardiac function between those patients who were successful and patients who were unsuccessful with the CPAP trial. In successful patients, cardiac output and stroke volume increased significantly without a change in heart rate or arterial pressure. Patients who were unsuccessful had no significant change in cardiac output, stroke volume, or heart rate but did have a significant increase in MAP in response to the CPAP trial.

Although highly variable, patterns in ectopy differed between the 2 groups of patients. In the successful group, ventricular ectopy decreased from 2 events per hour at baseline to 1 event per hour during the CPAP trial. In the unsuccessful group, ventricular ectopy was more prevalent at baseline and did not change during the CPAP trial. Supraventricular ectopic beats increased by about one third during the CPAP trial in the successful group, from 2.7 events per hour at baseline to 4.4 events per hour, and more than doubled in the unsuccessful group, from 2.8 events per hour to 6.5 events per hour.

Changes in plasma concentrations of catecholamines occurred in conjunction with changes in cardiac function. In the successful group, the epinephrine and norepinephrine concentrations during the CPAP trial were less than the values at baseline. In the unsuccessful group, both epinephrine and norepinephrine levels increased during the CPAP trial. Surprisingly, arterial blood gases and pulmonary variables measured at the end of the 2-hour CPAP trial did not differ significantly between the 2 groups.

Previous investigators23,24,47,48 reported cardiac instability in response to the institution of spontaneous ventilation. Our results support the importance of cardiac function and heart-lung interactions in patients receiving mechanical ventilation. In our study, the transition from mechanical to spontaneous ventilation was associated with significant hemodynamic changes in those patients who were able to successfully establish spontaneous ventilation. Successful patients increased cardiac output in response to the CPAP trial because of a significant increase in stroke volume. Reinstitution of spontaneous ventilation most likely generated reduced intrathoracic pressure to produce inspiration, which augmented the venous return gradient and increased venous return.20,46 Mitchell et al49 recently concluded that phasic alterations in venous return generated by mechanical ventilation modify cardiac function and output because of direct ventricular interaction. These investigators found that ventilatory maneuvers changed venous return and vena caval blood flow, shifted the interventricular septum, influenced left ventricular diastolic filling, and altered end-diastolic volume and stroke volume.

In our successful patients, stroke volume and subsequent cardiac output most likely were augmented via the Frank-Starling mechanism. This intrinsic property of cardiac muscle produced enhanced contractile performance in response to increased muscle length or stretch. Although the concept of length-dependent changes in stroke work has been documented and studied for more than 100 years, scientists still do not have a full explanation of the mechanisms that produce this effect.50–53

Moss and Fitzsimons53 presented potential contributing factors that produce greater calcium sensitivity in myocytes with more ventricular volume and greater myocyte stretch. Fiber diameter may be more important than fiber length in the Frank-Starling mechanism. Reduced interspace distance between the contractile proteins, actin and myosin, ensures greater proximity of the proteins with greater cross-bridge binding and increased contractile force.52,53 Evidence also suggests that cross-bridge binding involves positive cooperativity. Thus, the initial formation of cross bridges facilitates the formation of even more cross bridges with subsequently increased contractile force.54

Finally, the protein titin may be an important component of the Frank-Starling mechanism. This protein accounts for much of the passive stiffness of cardiac muscle. Changes in volume produce strain in this giant protein, which may pull the actin and myosin filaments closer together and increase the likelihood of cross-bridge formation.54–57 Those patients who were unsuccessful in the CPAP trial had no change in stroke volume and thus could not respond to alterations in intrathoracic pressure and venous return via the Frank-Starling mechanism. However, our data suggest that these patients did attempt to respond.


Successful patients increased cardiac output by increasing stroke volume in response to the CPAP trial.

 

Patients who were unsuccessful had a significant increase in catecholamine concentration and MAP during the CPAP trial, changes that indicate a sympathetic nervous system response to spontaneous ventilation. Because mean levels of arterial blood gases did not differ significantly between the 2 groups at the end of the CPAP trial, a likely cause of this increase in sympathetic activation is cardiovascular dysfunction in response to changes in intrathoracic pressure. The inability of the heart to respond to subsequent alterations in venous return may have produced an imbalance between oxygen demand and delivery. This imbalance generated sympathetic outflow to maintain organ perfusion and oxygen delivery. The resultant vasoconstriction indicated by the increase in MAP augmented left ventricular afterload, a change that might further impede ventricular ejection in patients with cardiac dysfunction.

In both groups of patients, heart rate during the CPAP trial did not differ significantly from heart rate at baseline. A primary determinant of heart rate is autonomic tone or the balance between sympathetic and parasympathetic stimulation. In the total sample of patients, mean catecholamine levels were elevated at baseline; the levels decreased during the CPAP trial in successful patients and increased in unsuccessful patients. Despite elevated catecholamine concentrations, heart rate did not significantly change during the CPAP trial in unsuccessful patients. This lack of response could indicate desensitization of ß-receptors in the myocardium, a common occurrence in patients with chronic elevations in neurohormone concentrations.58,59 The responsiveness of ß-receptors is also blunted with aging,60,61 but the mean age of our patients was 51 years, so age is not a likely explanation for the lack of response. This finding requires further investigation, because most likely many critically ill patients receiving mechanical ventilation have consistently elevated catecholamine levels that may be further increased in response to a stressor such as the reinstitution of spontaneous ventilation.62

Patterns of ectopy before and during discontinuation of mechanical ventilation have not previously been reported. Ectopic beats in particular influence ventricular filling time and oxygen delivery and so should be a concern in patients supported with mechanical ventilation. All patients in the study were in normal sinus rhythm. However, many of them had ventricular and supraventricular ectopic beats. Patients who were unsuccessful in the CPAP trial tended to have more ventricular ectopy at baseline than did successful patients, and the number of events per hour in the unsuccessful group did not change significantly during the CPAP trial. All patients experienced increased supraventricular ectopy during the CPAP trial.

These supraventricular ectopic beats may be related to changes in atrial and ventricular blood volume and increased afterload. This phenomenon, mechanoelectrical feedback, indicates that alterations in electrophysiological properties of cardiac muscle are produced by mechanical changes. The results of this phenomenon include shortening of the duration of action potentials, changes in the amplitudes of resting diastolic and systolic action potentials, and stimulation of early afterdepolarizations, with ectopic beats arising from myocardial areas experiencing the greatest degree of stretch.36


Patients who failed the trial had more ventricular ectopy on the ventilator and during the trial.

 

Pye and Cobbe35 found that acutely increased ventricular volume was arrhythmogenic, and Kamkin et al63 found an increased susceptibility to mechanical atrial stretch induced by volume after acute myocardial infarction. Sideris et al64 found that an acute increase in afterload was arrhythmogenic and that interventions to reduce afterload decreased arrhythmogenesis. In studies in both animals38,49,63 and humans,61,64–67 chronic ventricular dilatation consistently decreased ventricular action potential duration and refractoriness, changes that enhance the development of dysrhythmias. These findings provide evidence that our patients most likely had increases in atrial volume with the return to spontaneous ventilation and that atrial mechanical stretch increased the number of supraventricular ectopic beats.

In the unsuccessful patients in our study, an increase in afterload was suggested by a significant increase in MAP during the CPAP trial. This group also experienced the effects of sustained elevations of catecholamine level on cardiac action potential.68 Because current antiarrhythmic therapies are targeted toward electrical disturbances, these therapies may be ineffective in patients with dysrhythmias due to mechanical changes.36 Dysrhythmias induced by mechanical alterations may be more effectively managed by therapies such as preload and afterload reduction to enhance the mechanical function of the heart.


   Limitations
Top
 Abstract
 Review of the Literature
 Purpose
 Methods
 Results
 Discussion
 Limitations
Conclusions
 References
 
This investigation was a pilot study. Therefore, the sample consisted of a small number of heterogeneous patients; the small sample size reduced the power of the statistical tests. Strict inclusion and exclusion criteria limit the generalizability of the findings, but these data do provide support for continued investigation of cardiovascular function in other subpopulations of critically ill patients who require mechanical ventilation. Although data collection points were selected on the basis of previous studies of hemodynamic alterations that occur with the reinstitution of spontaneous ventilation after mechanical ventilation, the data provide only a snapshot of cardiac function at 2 time points. Significant alterations could have occurred at times other than those chosen for data collection.


   Conclusions
Top
 Abstract
 Review of the Literature
 Purpose
 Methods
 Results
 Discussion
 Limitations
 Conclusions
References
 
Slightly more than one third of the patients in the study experienced difficulty with spontaneous ventilation after a period of mechanical ventilation. Patterns of cardiac response differed significantly between the group who achieved spontaneous ventilation with the CPAP trial and the group who did not. Patterns in cardiac dysrhythmias were also apparent. Cardiovascular status and responses to the return to spontaneous ventilation should be systematically evaluated before, during, and after discontinuation of mechanical ventilation. Clear criteria for stable hemodynamic status should be determined and defined for consistency. Predictors of cardiac response to the stress of spontaneous ventilation should be identified and strategies should be used to optimize cardiac function to reduce duration of mechanical ventilation and the morbidity and mortality related to discontinuation of mechanical ventilation.


   ACKNOWLEDGMENTS
 
Research support for this investigation was provided by grant 1 R15 NR05059-01 from the National Institute of Nursing Research, an Agilent Technologies–American Association of Critical-Care Nurses research grant, and grant M01 RR00034 from a National Institutes of Health General Clinical Research Center.

To purchase 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{at}aacn.org.


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 Discussion
 Limitations
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