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Ann Thorac Surg 1997;64:148-153
© 1997 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Phrenic Nerve Injury After Coronary Artery Grafting: Is It Always Benign?

Departments of Cardiovascular Surgery and Radiology, Edith Wolfson Medical Center, Holon, and Sackler School of Medicine, Tel Aviv University,Tel Aviv, Israel

Accepted for publication January 21, 1997.

	Abstract

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Background. The purpose of this study was to evaluate the effect of phrenic nerve injury (PNI) occurring during coronary artery bypass grafting in patients with major chronic obstructive pulmonary disease (COPD).

Methods. Over a 42-month period, 1,303 patients underwent primary coronary artery bypass grafting. Sixty-seven (5.14%) had major COPD, and 29 (43.3%) of these 67 sustained PNI (group I). These patients were matched for age and ejection fraction with 29 CABG patients with COPD but without PNI (group II), 29 patients without COPD but with PNI (group III), and 29 patients with neither COPD nor PNI (group IV). The groups were compared on the basis of preoperative and operative factors and immediate and midterm morbidity and mortality.

Results. There were no significant differences between the groups with respect to hypertension, diabetes, ejection fraction, number of grafts, internal mammary artery use, cardiopulmonary bypass time, and ischemic time. Postoperatively, group I had a longer total hospitalization (group I, 11.7 days; group II, 7.8 days; group III, 7.8 days; and group IV, 6 days; p = 0.0001) and stay in the intensive care unit (I, 3.6 days; II, 2.2 days; III, 2.1 days; and IV, 1.2 days; p = 0.0023). More patients in group I required reintubation (I, 37.9%; II, 3.4%; III, 6.9%; and IV, 0%; p < 0.0001). Mean follow-up was 32.8 months (range, 7 to 48 months). Group I had more hospital readmissions (I, 78; II, 50; III, 61; and IV, 28; p < 0.007) and lower cumulative survival (I, 60.6%; II, 93%; III, 96.8%; and IV, 100%; p < 0.0015) compared with the other groups.

Conclusions. In patients with COPD, PNI during coronary artery bypass grafting has a major negative impact on immediate and midterm results.

	Introduction

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Chronic obstructive pulmonary disease (COPD) has been shown to be a significant risk factor for early and midterm mortality and morbidity in patients undergoing coronary artery bypass grafting (CABG) [1]. Patients with COPD have been shown to have longer hospital stays and reduced quality of life after CABG [1].

Patients undergoing CABG have an incidence of phrenic nerve paralysis that ranges from 10% to 60% [2–7]. Chronic obstructive pulmonary disease has been demonstrated to be a risk factor for phrenic nerve injury (PNI) in patients undergoing CABG [1]. Phrenic nerve injury is known to have a mild impact on morbidity and mortality in the CABG population at large [2, 5]. The purpose of this study was to evaluate the effect of PNI on morbidity and mortality in patients undergoing CABG with major COPD.

	Patients and Methods

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Between June 1991 and December 1994, 1,303 patients underwent primary CABG at our institution. Of these, 67 patients (5.14%) were considered to have major COPD. We defined patients with major COPD on the basis of the following criteria: the patient was actively followed up for COPD in the pulmonary clinic; the patient was being treated with medication for COPD; and the referring physician had to consider the COPD dominant to or codominant with the ischemic heart disease [1].

Of the 67 patients with major COPD, 29 (43.3%) had a PNI during CABG (group I). Another 29 patients had COPD but no PNI (group II). These patients were matched to group I on the basis of the date of operation. Group I was compared with a group of 29 patients without COPD who underwent CABG and sustained a PNI (group III). Group II patients were compared with 29 patients undergoing CABG who had neither major COPD or diaphragmatic injury (group IV, control group). The patients were matched for age, sex, ejection fraction, and date of operation.

For this study, heavy smoking was defined as more than 15 cigarettes per day for longer than 5 years.

The groups were evaluated for preoperative and operative characteristics. The postoperative course, including length of intensive care unit (ICU) stay, total hospitalization, morbidity, and 30-day mortality was evaluated.

Operative Techniques and Postoperative Monitoring
The operative techniques included a median sternotomy and single aortic and venous cannulation. The internal mammary artery (IMA) was harvested using cautery and was based on a pedicle 2 cm wide. The left pleural space was opened widely in all patients. The patients were cooled to 26°C, and iced saline solution was applied for topical hypothermia. Antegrade and combined antegrade and retrograde techniques of cardioplegia were employed. Early in the study, crystalloid cardioplegia was used; and later we switched to blood cardioplegia. Cardioplegia was administered intermittently every 20 minutes at a temperature of 4°C. For antegrade and retrograde cardioplegia, an initial dose of antegrade cardioplegia was given followed by retrograde cardioplegia every 20 minutes. The IMA graft was directed medially, and the pericardium was incised to allow the IMA to reach the left anterior descending coronary artery without tension. Proximal venous grafts were performed using a partial clamp.

During hospitalization, all patients were monitored continuously for arrhythmias. A bedside electronic monitor was used in the ICU, and telemetry to a control nursing station was used on the ward. Major arrhythmias were considered to be those occurring for more than 1 minute, those with malignant potential, or those causing hemodynamic compromise.

Follow-up
All patients or their families were contacted between June and August 1995. All survivors were seen in our clinic to evaluate the postoperative course. This evaluation included a history of all readmissions to the hospital and their causes. Patients were asked to assess their present quality of life as compared with their preoperative state in terms of exercise capability, breathing difficulty, and the ability to perform desired tasks.

All patients had chest roentgenograms preoperatively, before discharge, and at the last follow-up. These were evaluated by a radiologist (R.K.) unfamiliar with the patient's clinical status.

The postoperative roentgenograms were examined for evidence of a newly elevated diaphragm and other pulmonary complications. For the left hemidiaphragm to be considered paralyzed, the following criteria had to be met: the left hemidiaphragm was located below the right hemidiaphragm on the preoperative posteroanterior chest roentgenogram; the left hemidiaphragm was at least one rib higher than the right hemidiaphragm on the discharge posteroanterior chest roentgenogram; and the hemidiaphragm either had returned to its normal location by late follow-up or was confirmed by ultrasound to be paralyzed at that time. No paralyzed right hemidiaphragm was present in this study. All diaphragms defined as being paralyzed (groups I and III) were checked by ultrasound at the last follow-up to determine the diaphragmatic function.

Pulmonary function tests (forced expiratory volume in 1 second [FEV₁] and forced vital capacity) were performed on all patients before operation and on all survivors at the last follow-up.

Statistical Analysis
One-way analysis of variance was used to compare the overall means of the four groups. In addition, contrasts were calculated to test the mean difference of specific pairwise comparisons. Pearson's ² test, with three degrees of freedom, was used for the comparison of percent presentation of characteristics in the four groups. Life-table survival was calculated for each group, and relevant pairwise comparisons of cumulative survival were tested with the Kaplan-Meier log-rank statistic. Assumptions of all these tests were checked and found to be satisfactory.

	Results

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Preoperative Characteristics
Preoperative characteristics of all four groups are shown in Table 1. There were no significant differences in the demographic data for the groups. Operative risk factors, including diabetes, hypertension, unstable angina, previous myocardial infarction, and ventricular ejection fraction, were similar in the groups. Among the COPD patients (groups I and II), there were more heavy smokers and more patients with substantial arrhythmias than in the patients without COPD (groups III and IV). There were no significant differences in these factors between groups I and II and between groups III and IV.

View larger version (22K): [in this window] [in a new window]   Fig 1. . Cumulative survival curves demonstrate reduced survival over midterm follow-up for patients with chronic obstructive pulmonary disease sustaining phrenic nerve injury during coronary artery bypass grafting (group I).

MORBIDITY.
During follow-up, there were significantly more complications among group I patients. The readmissions resulting from complications are summarized in Table 5. Group I had significantly more total readmissions; a higher proportion of patients with multiple readmissions was also found in this group. For the select group of patients having multiple readmissions, respiratory complications were the primary reason in group I only (Fig 2).

View larger version (33K): [in this window] [in a new window]   Fig 2. . Causes of readmission after coronary artery bypass grafting in patients with two or more readmissions. In patients with chronic obstructive pulmonary disease (COPD) and phrenic nerve injury (PNI) (COPD + PNI) (group I), the primary cause is respiratory. In groups II (COPD), III (PNI), and IV (CONTROL), the primary cause of readmission is cardiac related.

A comparison of preoperative and late postoperative pulmonary function is shown in Table 2. Groups I and II had significantly reduced preoperative values for FEV₁ compared with groups III and IV (p = 0.0001). There was a reduction in FEV₁ in groups II, III, and IV from the preoperative to late follow-up studies.

QUALITY OF LIFE.
The results of our quality of life survey are shown in Figure 3. Patients with COPD (groups I and II) have a lesser quality of life, and in these patients, diaphragmatic injury further reduces the benefits of CABG.

View larger version (16K): [in this window] [in a new window]   Fig 3. . Quality of life after coronary artery bypass grafting. Preoperative chronic obstructive pulmonary disease (COPD) combined with intraoperative phrenic nerve injury (PNI) causes substantial reduction in quality of life at midterm follow-up. Numerals on ordinate are percentages.

	Comment

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

The incidence of PNI after CABG ranges from 10% to 60% [2, 6, 9, 10]. Recent reports [3, 4] on patients undergoing CABG with cold hypothermia continue to show an incidence of diaphragmatic injury of 32% to 58%. Despite the high rate of injury, the clinical impact of such injury has been reported to be mild [2,11–14], with up to 90% of these injuries resolving within 1 year [7, 15].

Chronic obstructive pulmonary disease has been shown to be associated with an increased incidence of PNI [1]. In the present study, we have demonstrated that PNI during CABG has highly significant clinical consequences for patients with major COPD.

Pulmonary Complications
Previous studies [16–18] have shown that in patients undergoing CABG, the FEV₁ will be reduced to two thirds of its previous value. It has been found that patients with major COPD have increased pulmonary complications and longer ICU and hospital stays after CABG [1]. In the present study, we confirmed this effect of COPD on CABG patients, but within the total COPD group (groups I and II), we were able to demonstrate a highly morbid effect of PNI. Within the overall COPD group, patients with PNI had a longer hospital stay, a longer ICU stay, and a greater incidence of reintubation or prolonged intubation than those without PNI.

Arrhythmias
The association of COPD with an increased incidence of ventricular and supraventricular arrhythmias is well established [19, 20]. Chronic obstructive pulmonary disease has also been identified as a risk factor for major postoperative arrhythmias in patients undergoing CABG [1, 21]. Our present study confirms this. Within the overall COPD group, PNI did not increase the incidence of postoperative arrhythmias, thus implying that most of the acute morbidity caused by PNI is pulmonary in nature.

Reversal of Phrenic Nerve Injury
Follow-up of up to 19 months has been reported for PNI [5, 7, 15]. The recovery has been studied physiologically [5], by roentgenography [7], and by electric stimulation [6]. Phrenic nerve regeneration is estimated at a rate of 1 mm/d [7]. On the basis of these studies, phrenic nerve recovery occurs at least partially in 75% to 90% of patients with such injury. Our study reports a 30-month follow-up with ultrasound evaluations. We found eight (28%) of 28 diaphragms still paralyzed in group III patients and 5 (24%) of 21 in patients with COPD. These data are consistent with those in the literature [5, 7]. The high number of diaphragms that remained paralyzed makes it highly unlikely that the paralysis in all was due to phrenic nerve transection. Thus, our study demonstrates that PNI caused by hypothermia or ischemia can persist for up to 44 months. Our data cannot demonstrate an effect of COPD regarding percentage of patients who recover phrenic nerve function or the timing of that recovery.

Functionally, we could not demonstrate a reduction in pulmonary function between groups I and III at last follow-up. This is probably due to the fact that patients with COPD who experienced major pulmonary embarrassment because of PNI died during follow-up. Thus, the patients with the greatest pulmonary effects of PNI in group I were probably not available for reevaluation at last follow-up.

Mortality
A preoperative FEV₁ of less than 1.25 has been shown to increase acute postoperative morbidity in CABG patients [8]. Chronic obstructive pulmonary disease has been demonstrated to be a significant factor in intermediate survival in CABG patients [1]. Our present study confirms this finding. However, it clearly indicates that the great majority of patients who died by midterm follow-up were patients with COPD who sustained a PNI during the CABG procedure (see Fig 1).

Quality of Life
Quality of life after CABG, from both the cardiac and the functional standpoint, is good [22]. Chronic obstructive pulmonary disease has been shown to reduce the functional results of CABG in the intermediate follow-up period [1]. In the present study, we have been able to confirm this. Further, we have been able to demonstrate that within the total COPD group, PNI further reduces quality of life. As follow-up progressed, group I patients continued to have recurrent respiratory problems that led to multiple hospital admissions and reduced their functional ability, despite apparently adequate cardiac function after operation.

Limitations of Study
There are a number of limitations to our study. First, the study is retrospective in the selection of patients. Within this constraint, we defined PNI as precisely as possible. However, we cannot exclude the possibility that some of these patients had left lower lobe atelectasis that raised the left diaphragm and mimicked PNI. Second, our study cannot identify the cause of PNI in these patients. It is known that iced saline solution (a practice now abandoned at our institution) can cause PNI, as can cautery dissection of the IMA and splitting the pericardium to shorten the course of the IMA graft. As all these techniques were practiced in all these patients, we cannot identify a specific cause for PNI in this patient population. Finally, the best way to prove that PNI in COPD patients contributes to mortality would be to perform multivariate analysis on our entire population of 1,303 patients. However, we lack sufficient follow-up on all 1,303 patients; therefore, a case-controlled study was performed.

Recognizing these limitations, we believe the following conclusions are warranted: clinical COPD is a significant cause of morbidity and mortality after CABG; PNI in such patients is a malignant complication that increases immediate and midterm morbidity and mortality; and the reduced benefit of CABG reported for patients with COPD is further reduced in those patients sustaining a PNI during CABG.

We make the following two recommendations: in patients with major clinical COPD, indications for CABG should be restricted; and in patients with major COPD undergoing CABG, great care should be taken to avoid PNI. Thus, the following proposals should be adopted for these patients: Topical iced saline slush for cooling the heart is contraindicated. Consideration should be given to the use of tepid or warm cardioplegia. Use of IMA grafts should be restricted to young patients. When IMA grafts are used, excessive mobilization of the artery should be avoided to prevent ischemic [6] or proximity injury to the phrenic nerve; in situations where such mobilization is required to perform an in situ left IMA graft, a free IMA graft should be used instead.

	Acknowledgments

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
This report was prepared in consultation with Diklah Geva, MSc, who performed the statistical calculations, and with the technical assistance of Sally Esakov, BA.

	Footnotes

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Address reprint requests to Dr Cohen, Department of Cardiovascular Surgery, Edith Wolfson Medical Center, PO Box 5, Holon 58100, Israel.

	References

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Amram J. Cohen Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cohen, A. J. Articles by Schachner, A. Search for Related Content PubMed PubMed Citation Articles by Cohen, A. J. Articles by Schachner, A.