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Postoperative Phrenic Nerve Palsy in Patients with Open-Heart Surgery
Postoperative Phrenic Nerve Palsy in Patients with Open-Heart Surgery Omkar N. Markand, M.D., F.R.C.P.(C), S. S. Moorthy, M.D., Yousuf Mahomed, M.D., Robert D. King, M.D., and John W. Brown, M.D. ABSTRACT We prospectively studied patients undergoing open-heart surgical procedures to evaluate the role of phrenic nerve palsy in the causation of the high incidence of pulmonary complications reported in these patients. Although atelectasis, or infiltrates, or both developed in the left lower lobe of 98% of the patients (43 of 44) with or without similar changes on the right side, only 5 (11%)of the 44 patients had diaphragmatic dysfunction following operation. in 1, the left phrenic nerve became inexcitable; 2 had paresis of the left hemidiaphragm, and 2 had paresis of the right hemidiaphragm. Although damage to the phrenic nerve can occur during open-heart operations, a relatively low incidence of this complication does not support it as the major cause of postoperative pulmonary complications. Atelectasis, usually of the left lower lobe, has been recognized as a common postoperative complication in patients undergoing open-heart surgical procedures, but the cause has remained controversial. Mechanical factors, such as retraction of the left lower lobe during operation or postoperative gastric distention, have been considered by some, whereas others have implied transient paresis of the left hemidiaphragm secondary to surgical or hypothermic injury to the phrenic nerve [l, 21. We carried out a prospective study of patients undergoing open-heart surgical procedures to evaluate their diaphragmatic function by transcutaneous phrenic nerve stimulation in the neck before and after the operation.
Material and Methods Fifty patients undergoing open-heart procedures at the Indiana University Hospital from January to June, 1983, were included in the study. The study had prior approval by the Indiana University School of Medicine committee on protection of human subjects. Informed consent was obtained before each patient entered the study. The patients ranged in age from 31 to 72 years with a mean age of 56 years. There were 38 men and 12 women. The surgical procedures included 35 coronary artery bypass operations, 7 aortic valve replacements, 4 mitral valve replacements, 1 combined aortic and mitral valve replacement, 2 combined coronary artery bypass From the Departments of Neurology, Anesthesia, and Surgery, Indiana University School of Medicine, Indianapolis, IN. Accepted for publication Mar 30, 1984. Address reprint requests to Dr. Markand, Department of Neurology, Riley A599N, 702 Barnhill Dr, Indianapolis, IN 46223.
68
and aortic valve replacement procedures, and 1 repair of a congenital atrial septa1 defect. None of the patients undergoing coronary artery bypass in this series had internal mammary artery grafts. Phrenic nerve conduction was assessed usually 1 to 2 days before the operation and repeated 6 to 8 days after the operation, by which time the lateral part of the lower chest was free of bandages and a satisfactory recording could be obtained. We recently described the technique of transcutaneous phrenic nerve stimulation in detail [ 3 ] . In short, the left and right phrenic nerves were stimulated percutaneously at the posterior border of the sternocleidomastoid muscles at the level of the upper part of the thyroid cartilage. The diaphragmatic potential was recorded from surface disc electrodes placed over the ipsilateral seventh intercostal space close to the costal margin (7CS) with reference to an electrode over the xiphoid process (XP) or the opposite knee. The graphs were plotted such that the positivity at the 7CS electrode resulted in an upgoing waveform. To ensure exactly the same location of the XP and 7CS recording electrodes for the preoperative and postoperative phrenic studies, distances were measured in each patient between the suprasternal notch and XP electrode and between the XP and the two 7CS electrodes at the time of preoperative assessment. These measurements allowed proper placement of electrodes during the postoperative study when the landmarks were not easily identifiable because of the midsternal incision and the associated superficial edema. A diaphragmatic potential of less than 0.4 mV in amplitude or more than 10 msec in latency was considered abnormal. Also, a leftkight amplitude ratio of the diaphragmatic potential of more than 2.0 or less than 0.5 was considered abnormal. All patients had radiographs of the chest before the operation and at variable intervals (usually three to five times) during the first week after the operation. The presence and location of infiltrates and atelectasis and the position of the hemidiaphragm were noted for each examination. We also obtained the following data: duration of cardiopulmonary bypass, use of topical ice or cold solution for cardiac cooling, lowest myocardial temperature, length of intubation, and duration of hospital stay. Student t and chi-square tests were used for statistical analysis; a p value less than 0.05 was considered statistically significant. During the same study period, an additional 7 patients were evaluated with phrenic studies because they had respiratory difficulty after cardiothoracic surgical procedures.
69 Markand et al: Phrenic Nerve Palsy after Open-Heart Surgery
Results All 50 patients included in the study had preoperative assessment of their phrenic nerve function, but postoperative evaluation could be completed in only 44 patients. Four patients declined postoperative phrenic studies because of discomfort associated with the electrical stimulation of the phrenic nerves during the preoperative evaluation. Two patients could not be restudied because the electrophysiologist (0.N. M.) was not available to perform the test. Thus, data were analyzed for the 44 patients who had both preoperative and postoperative electrophysiological studies. The preoperative radiographs of the chest showed no infiltrate or atelectasis except in 1 patient with subsegmental bibasilar atelectasis that was more extensive on the left side. Postoperatively all patients had three or more studies in the first week after operation. Fortythree patients (98%)showed atelectasis, or infiltrates, or both in one or more of the postoperative radiographs. Changes occurred only in the left base in 13 (30%), whereas 30 (70%) had bilateral changes. In patients with bilateral pulmonary atelectasis, infiltrates, or both, the alterations generally were more severe on the left side. The changes initially occurred on the left side with subsequent development of similar abnormalities on the
right side. The chest radiographs usually showed more severe alterations 2 days after the operation rather than in the immediate postoperative period. In all patients, the amplitude and the latency of the diaphragmatic potential were normal in the preoperative studies. Postoperatively, 5 patients had marked changes in their phrenic studies (Table 1).Patient 1 had the most prominent change; his left phrenic nerve became totally inexcitable. It remained so for four months before the function returned in the last study performed 28 weeks after the operation (Fig 1).In 2 patients (Nos. 3, 4, see Table 1) the left and in 2 (Nos. 2, 5), the right phrenic responses were markedly reduced in amplitude (Fig 2). The 3 patients with abnormal electrical responses to left phrenic stimulation also demonstrated elevation of the left hemidiaphragm on chest radiograph. On the other hand, the 2 patients with right phrenic abnormality on electrical study failed to show radiological findings of hemidiaphragmatic paresis. After the 5 patients with obvious postoperative changes in phrenic nerve function were excluded, the mean values for amplitude and latency of the diaphragmatic potential in the remaining 39 patients in the operative and postoperative studies were compared (Table 2). The latency of the right and left diaphragmatic re-
Table 1. Preoperative and Postoperative Studies in 5 Patients Who Had Substantial Changes in Phrenic Nerzv Conduction Phrenic Nerve Studies Amplitude (mV)
Latency (msec) ~
_
_
_
~
Patient No., Age (yr), Sex
Operation(s)
Time of Study
Right
Left
Right
Left
Comments
1. 54, M
CABG
Preop Postop, Postop, Postop, Postop, Postop, Preop Postop,
0.80 X X X X 0.40 0.60 0.70
7.9 8.6 7.2 7.5 7.3 7.6 6.5 7.4
8.9 X
Extubated on POD 1; infiltrates and pleural effusion in left lower lobe; elevated L hemidiap hragm
2 wk
1.00 0.80 0.75 0.60 0.70 0.80 0.60 0.30
Preop Postop, 1 wk Postop, 2 wk
0.90 0.60 0.60
0.95 0.10 0.20
8.9 8.9 9.6
7.9 8.3 10.5
Preop Postop, Postop, Postop, Postop, Preop Postop, Postop,
0.60 0.60 0.45 0.45 0.45 0.60 0.30 0.26
0.60 0.16 0.12 0.16 0.26 0.90 0.60 0.75
7.9 8.0 7.6 7.4 7.6 6.3 7.2 7.1
8.2 7.7 9.1 9.6 8.5 6.2 6.5 6.3
2. 69, F
3. 70, F
4. 57, F
5. 59, M
MVR
CABG + resection of LV aneurysm AVR + MVR
CABG
CABG = coronary artery bypass grafting; MVR ventricular; POD = postoperative day.
=
1 wk 6 wk 10 wk 15 wk 28 wk
1.5 wk 3 wk 12 wk 22 wk
1 wk 3 wk
X X
X 14.1 6.2 7.0
mitral valve replacement; AVR = aortic valve replacement; X
=
Extubated on POD 2; right-sided atelectasis and infiltrates; bilateral pleural effusion Extubated on POD 1; bilateral atelectasis and infiltrates; bilateral pleural effusion; elevated L hemidiaphragm Extubated on POD 1; bilateral basal atelectasis; elevated L hemidiaphragm
Extubated on POD 1; bilateral basal atelectasis and infiltrates; right-sided pleural effusion no diaphragmatic potential; LV
=
left
70 The Annals of Thoracic Surgery Vol 39 No 1 January 1985
RT PHRENIC N.
L T PHRENIC N.
&*
C
X P ICS
A
I
-
__
~
ID
1 5 0 0 p V
10msec
Fig 1 . Serial phrenic nerve studies in Patient I (see Table 1) (A) one day before coronary bypass and ( B ) 1 , (C) 6 , ( D ) 10, and (€) 28 weeks after the operation. The left phrenic nerve became inexcitable after operation. Function returned in the last study, but the diaphragmatic potential is of lower amplitude and prolonged latency (14.0 rnsec).
sponses showed no major change after the operation. There was a tendency for the amplitude of the diaphragmatic potential to decrease in the postoperative study, but the difference reached statistical significance only for right phrenic stimulation. Following operation, 38 patients (86%)were extubated within a day. Five were extubated 2 days and 1, 4 days after the operation. Of the 5 patients who had marked postoperative alteration of the phrenic nerve study, only Patient 2 needed a longer period (2 days) of assisted ventilation after the operation. Among the 44 patients, 26 had intermittent cold blood potassium cardioplegia without topical myocardial cooling and 18 had topical cooling with either cold saline or ice-slushed saline solution. Phrenic palsy developed in 2 patients from the former group (without topical cooling) and in 3 from the latter (with topical cooling); the difference was not statistically significant. The lowest myocardial temperature recorded in the patients without phrenic palsy was 12.08" f 2.13"Ccompared with 12.24' k 2.11"Cin those with postoperative phrenic palsy. The level of systemic hypothermia was also similar (24" to
10 msec
rnOCC
Fig 2. Phrenic nerve studies in Patient 3 (see Table 1) ( A ) one day before, ( B ) 1 week after, and (C) 2 weeks after coronay arte y bypass and resection of left ventricular aneurysm. Studies show marked reduction in the amplitude of the diaphragmatic potential postoperatively on left phrenic stimulation. (XP = electrode placed over the xiphoid process; 7CS = electrode placed over the ipsilateral seventh intercostal space close to the costal margin; K = electrode placed over the knee.)
25°C) in patients with and without phrenic palsy. Duration of cardiopulmonary bypass was found to be longer in the patients with phrenic palsy: 170.40 k 38.44 minutes versus 126.08 k 33.18 minutes in patients without phrenic palsy. This difference was statistically significant ( p < 0.02). Seven patients were referred for phrenic studies because they could not be weaned off mechanical ventilation or had respiratory difficulties following cardiothoracic operations. These patients were derived from a total of 224 patients who had open-heart procedures Table 2. Preoperative and Postoperative Studies of Diaphragmatic Potential in 39 Patients" Variable Right phrenic nerve stimulation Amplitude (mV) Latency (msec) Left phrenic nerve stimulation Amplitude (mV) Latency (msec)
Preoperahve Study
Postoperative Study
Significance
0.81 C 0.20 7.86 2 0.76
0.71 2 0.20 7.91 t- 0.71
y < 0.05 NS
0.78 2 0.23 7.85 2 0.68b
0.70 0.21 7.92 t- 0.7Ib
*
NS NS
'Values shown are mean f standard deviation. bFor this study, N = 38; in 1 patient, diaphragmatic potential on left phrenic stimulation did not have a good "takeoff" to determine latency accurately.
NS
=
not significant.
71 Markand et al: Phrenic Nerve Palsy after Open-Heart Surgery
Table 3 . Phrenic Nerve Conduction in 7 Patients Who Had Respiratory Difficulties following Cardiothoracic Operations Phrenic Nerve Studies Amplitude Patient No., Age, Sex
Operation(s)
1. 3 mo, Ma
Repair of coarctation
2. 73 yr, Ma
Cholecystectomy, CABG (5 yr previously) Repair of mitral insufficiency
3. 9 mo, F
Interval after Operation
Latency (msec)
(mv)
Right
Left
Right
4d
0.90
X
6d 9 wk 11 wk 7d
X X X 0.80
X X X 1.00
X X X 4.5
X X X 4.0
4.1
Left
Comments
X
Extubated on POD 10; bilateral infiltrates; elevated L hemidiaphragm Patient remained on respirator until his death 3 mo after cholecystectomy Extubated on POD 15; bilateral infiltrates; elevated R diaphragm Extubated on POD 13; bilateral infiltrates; pleural effusion Extubated on POD 1; bilateral infiltrates; elevated L hemidiaphragm Extubated on POD 12; atelectasis and pleural effusion in left lower lobe
4. 4 yr, F
Repair of AV canal
8d
0.55
0.40
4.3
4.4
5. 4 yr, F
Repair of atrial septa1 defect
4d
0.55
0.60
4.9
4.9
6. 71 yr, F”
CABG
0.18 0.20 0.20 0.36 0.40 0.45
X X
8.5 8.7 8.5 7.3 7.3 10.0
X X X 13.5 9.4 9.5
7. 63 yr, M
CABG
12 d 2.5 wk 8 wk 12 wk 20 wk 7d
X 0.16 0.44 0.65
Extubated on POD 3; atelectasis of left lower lobe; bilateral pleural effusion
“Patient had abnormal phrenic nerve studies.
CABG = coronary artery bypass grafting; AV
=
atrioventricular; X
=
no diaphragmatic potential; POD
during the study period but were not included in the prospective study. They did not have preoperative assessment of phrenic nerve function. Electrical stimulation of their phrenic nerves demonstrated evidence of unilateral diaphragmatic paralysis in 1 and bilateral dysfunction in 2 of these patients; phrenic study results were normal in the remaining 4 patients (Table 3). One patient (No. 2; see Table 3) studied a week after removal of the gallbladder for acute cholecystitis, showed inexcitable phrenic nerves bilaterally. Two additional studies over the succeeding three months also failed to evoke a response even on intense stimulation of his phrenic nerves. This patient had undergone coronary artery bypass grafting five years previously when a left phrenic paralysis developed; his chest radiograph before the gallbladder operation showed an elevated left hemidiaphragm. Damage to the diaphragm itself or to the phrenic nerve during cholecystectomy resulted in bilateral inexcitable phrenic nerves that required artificial ventilation until the patient’s death three months after the gallbladder operation. In a 3-month-old child (Patient 1; see Table 3) the left phrenic nerve was found to be inexcitable following repair of coarctation of the aorta, but a normal diaphrag-
=
postoperative day
matic response was recorded on the other side. In the remaining patient (No. 6; see Table 3) who had coronary artery bypass grafting, inexcitable left phrenic nerves were associated with a reduced response on right-sided stimulation. Serial studies in this patient demonstrated a partial return of function by twelve weeks and almost normal function by twenty weeks after the operation. The phrenic latency gradually decreased as the diaphragmatic potential attained normal amplitude. All 7 patients had pulmonary atelectasis, or infiltrates, or both, often bilaterally, and the changes were not appreciably different in the patients with or without abnormal phrenic nerve conduction studies. Three patients with abnormal phrenic nerve studies had radiographic evidence of diaphragmatic paralysis on the ipsilateral side. Two patients (Nos. 3, 5; see Table 3) were suspected of having diaphragmatic paralysis on radiological grounds but had normal and symmetrical responses on phrenic nerve stimulation.
Comment Infiltrates or atelectasis or both developed in the left lower lobe of 98% (43 of 44) of patients with or without a similar involvement of the right lower lobe in the im-
72 The Annals of Thoracic Surgery Vol 39 No 1 January 1985
mediate postoperative period. These findings are similar to the observations of Good and colleagues [l]and Benjamin and associates [2], who reported an incidence of more than 85% for similar complications following coronary artery bypass. Three causes have been proposed for such a high incidence of postoperative pulmonary complications: (1)gastric distention following operation with elevation of the hemidiaphragm, (2) damage to the phrenic nerves as a result of direct surgical trauma or from topical hypothermia secondary to ice cooling of the heart, and (3) trauma to the lung, particularly the left lower lobe secondary to retraction during operation. The role of gastric distention can be virtually eliminated because nasogastric tubes inserted before the operation failed to prevent pulmonary complications. Mechanisms similar to the postoperative atelectasis observed in upper abdominal operations are also not responsible, as the routine use of positive end-expiratory pressure has been found to be ineffective in preventing pulmonary complications following coronary artery bypass grafting [l]. Transient paralysis of the left phrenic nerve resulting from hypothermic injury secondary to ice cooling of the heart has been strongly supported by evidence from Benjamin and co-workers [2]. They reported left lower lobe infiltrates and atelectasis in 63 to 85% of their patients who underwent operation with topical cooling of the heart using ice compared with an incidence of 32.5% in patients without such intraoperative cooling. These authors found a high incidence (69.2%)of abnormal diaphragmatic motion in the chest radiographs of patients with left lower lobe abnormality, but they did not carry out electrophysiological studies of the phrenic nerves. That transient phrenic nerve dysfunction can develop secondary to hypothermic injury has been shown experimentally by Marco and colleagues [4], who found that application of ice to the phrenic nerves of dogs for 30 to 60 minutes resulted in paralysis lasting one to four weeks. Whether this paralysis is the sole mechanism for the almost invariable development of infiltrates and atelectasis observed after open-heart operations in human beings, however, can be questioned on several grounds. First, a high incidence of pulmonary complications following open-heart surgery has been reported, even when ice cooling of the heart was not carried out. In our series all but 1 of the patients had these postoperative complications. Second, we and other groups [l] have shown that the incidence of atelectasis and infiltrates is higher 2 or more days following rather than immediately after operation, a finding that would be difficult to explain if the changes were due to hypothermic phrenic nerve injury sustained during the operation. Third, our electrophysiological evaluation of phrenic nerve-diaphragm function assessed in patients before and after open-heart procedures established that 89% (39/44) of the patients had no marked changes in phrenic nerve conduction following operation. We think that trauma to the lungs secondary to retraction and subsequent pulmonary contusion is probably
the most common cause for the high incidence of pulmonary complications seen in the immediate postoperative period following open-heart surgical procedures. Decreased ability to cough secondary to chest pain and sedation with resultant retained secretions may be additional causative factors. The more common and severe involvement of the left side probably reflects more severe operative trauma due to the retraction of the left lung. There is also an increasing body of evidence that microaggregates of platelets, fibrin, and leukocytes lodging in the pulmonary vasculature during extracorporeal circulation may contribute to pulmonary complications after open-heart surgery [5]. Undoubtedly a small proportion of patients do sustain phrenic nerve damage during cardiothoracic operations; the incidence of this complication was 11%(5 of 44 patients) in our prospective study. The incidence of total phrenic paralysis, however, was lower: only 1 of the 44 had total lack of response on stimulation of the left phrenic nerve after the operation. Three other patients with total phrenic nerve paralysis were identified among 224 open-heart operations conducted during the same study period-an incidence of approximately 1.5%. Others [6-81 have reported a similar incidence of this complication following cardiothoracic operations. We think that phrenic nerve damage is primarily a stretch injury, which may occur during retraction of the sternum or prolonged pericardial stretch applied through weights during the operation. Although the use of topical cardiac cooling or the lowest myocardial temperature during operation had no major influence when considered individually, hypothermic injury may play an important additive role in causing phrenic palsy. Longer duration of cardiopulmonary bypass in patients in whom phrenic palsy developed would support the notion that longer duration of stretch and prolonged systemic hypothermia may be crucial etiological factors. Reducing the duration of both the systemic hypothermia and the pericardial stretch during operation may help reduce the incidence of intraoperative phrenic injury. The present investigation had one notable limitation in that the electrophysiological evaluation was performed at least 6 days after the operation because of the technical difficulties in the immediate postoperative period. It is therefore possible that we may have missed cases of transient postoperative diaphragmatic dysfunction, which might have recovered by the time of the electrical evaluation. Nonetheless, our investigation strongly suggests that diaphragmatic paresis of a clinically significant degree occurs in a much smaller percentage of patients after open-heart procedures than the incidence of postoperative pulmonary complications would dictate. We found no change in the latency but a slight decrease (10%) in the mean amplitude of the diaphragmatic potential following open-heart operation (see Table 2). The change, which was slightly greater for the right-sided stimulation, remains unexplained. It may be due to increased tissue impedance secondary to postop-
73 Markand et al: Phrenic Nerve Palsy after Open-Heart Surgery
erative alterations in the intrathoracic and superficial tissues. The effect of phrenic nerve palsy on the mechanics of respiration varies according to the status of other respiratory muscles and associated pulmonary complications. Unilateral phrenic nerve palsy in the presence of pulmonary infiltrates or effusion may compromise ventilation to the extent that prolonged ventilatory support is required, as was the case in 3 of our 4 patients who had total paralysis of the diaphragm on one or both sides. The only patient with bilateral inexcitable phrenic nerves required mechanical ventilation until his death. Stephens [6] reported that compared with older children, infants with unilateral phrenic paralysis did less well in the immediate postoperative period because they more commonly required prolonged ventilatory support and, rarely, diaphragmatic plication. The long-term outcome of unilateral phrenic paralysis, even when complete, appears to be favorable, at least in adults, because all of the patients in our series attained normal ventilatory status after 2 to 3 weeks. The stretch injury to the phrenic nerve is mainly to the axons, and the integrity of the nerve remains largely intact; hence, recovery may be expected. The time taken for recovery depends on the site of injury and the rate of regeneration. When the phrenic nerve was crushed in the neck as a therapeutic procedure to treat tuberculosis, the majority of patients had return of diaphragmatic motion over the following six months [9]. Similar nerve injury in the thorax is expected to take a shorter period for recovery. Three of our 4 patients who had follow-up studies extending beyond ten weeks of the operation showed evidence of recovery of the phrenic nerve function; the recovery time appears to be between three and six months. In the past phrenic nerve paralysis has been detected largely by radiological investigations. Electrophysiological assessment of the phrenic nerve function has been mentioned only rarely in patients who experienced phrenic paralysis following cardiothoracic operations [lo-121. An elevated hemidiaphragm in radiographs of the chest with atelectasis and infiltrates of the lower lobe on that side is suggestive of unilateral phrenic paralysis, but local pulmonary pathology, eventration of the diaphragm, or infradiaphragmatic disease may produce similar findings. A fluoroscopic examination of the chest that demonstrates reduced excursion of the hemidiaphragm and paradoxical motion is considered diagnostic of diaphragmatic paralysis, although fluoroscopy may be delayed because of the condition of the patient. The findings also may be difficult to interpret, particularly in the presence of pleural effusion or atelectasis. Un-
equivocal evidence of phrenic nerve damage, on the other hand, can be quickly established by percutaneous phrenic nerve stimulation. The technique is easy, can be performed at the bedside of the patient, and can be repeated as often as desired. Serial studies may also provide the earliest evidence of return of phrenic nerve function. Therefore, electrophysiological evaluation of phrenic nerves should be included in the assessment of patients who have ventilatory difficulties, pulmonary atelectasis and infiltrates, and elevation of hemidiaphragm in the postoperative period following cardiothoracic surgical procedures. We thank the cardiovascular surgical house staff for their cooperation in obtaining preoperative and postoperative phrenic nerve studies on patients in their care. We also thank Mrs. Martha Stanley for typing the manuscript.
References 1. Good JT Jr, Wolz JF, Andersen JT, et al: The routine use of positive end-expiratory pressure after open heart surgery. Chest 76~397,1979 2. Benjamin JJ, Cascade PN, Rubenfire M, et al: Left lower lobe atelectasis and consolidation following cardiac surgery: the effect of topical cooling on the phrenic nerve. Radiology 142:11, 1982 3. Markand ON, Kincaid JC, Pourmand RA, et al: Electrophysiologic evaluation of diaphragm by transcutaneous phrenic nerve stimulation. Neurology 34:604, 1984 4. Marco JD, Hahn JW, Barner HB: Topical cardiac hypothermia and phrenic nerve injury. Ann Thorac Surg 23235, 1977 5. Ratliff NB, Young WG Jr, Hackel DB, et al: Pulmonary injury secondary to extracorporeal circulation. J Thorac Cardiovasc Surg 65:425, 1973 6. Stephens JW: Neurological sequelae of congenital heart surgery. Arch Neurol 7450, 1962 7. Mickell JJ, Oh KS, Siewers RD, et al: Clinical implications of postoperative unilateral phrenic nerve paralysis. J Thorac Cardiovasc Surg 76297, 1978 8. Lederman RJ, Breuer AC, Hanson JR, et al: Peripheral nervous system complication of coronary artery bypass graft surgery. Ann Neurol 12:297, 1982 9. Iverson LI, Mittal A, Dugan DJ, et al: Injuries to the phrenic nerve resulting in diaphragmatic paralysis with special reference to stretch trauma. Am J Surg 132:263, 1976 10. Davis JN: Phrenic nerve conduction in man. J Neurol Neurosurg Psychiatry 30:420, 1967 11. Shaw RK, Glenn WWL, Hogan JF, Phelps ML: Electrophysiological evaluation of phrenic nerve function in candidates for diaphragm pacing. J Neurosurg 53345, 1980 12. Moosa A: Phrenic nerve conduction in children. Dev Med Child Neurol 23:434, 1981
Material and Methods Fifty patients undergoing open-heart procedures at the Indiana University Hospital from January to June, 1983, were included in the study. The study had prior approval by the Indiana University School of Medicine committee on protection of human subjects. Informed consent was obtained before each patient entered the study. The patients ranged in age from 31 to 72 years with a mean age of 56 years. There were 38 men and 12 women. The surgical procedures included 35 coronary artery bypass operations, 7 aortic valve replacements, 4 mitral valve replacements, 1 combined aortic and mitral valve replacement, 2 combined coronary artery bypass From the Departments of Neurology, Anesthesia, and Surgery, Indiana University School of Medicine, Indianapolis, IN. Accepted for publication Mar 30, 1984. Address reprint requests to Dr. Markand, Department of Neurology, Riley A599N, 702 Barnhill Dr, Indianapolis, IN 46223.
68
and aortic valve replacement procedures, and 1 repair of a congenital atrial septa1 defect. None of the patients undergoing coronary artery bypass in this series had internal mammary artery grafts. Phrenic nerve conduction was assessed usually 1 to 2 days before the operation and repeated 6 to 8 days after the operation, by which time the lateral part of the lower chest was free of bandages and a satisfactory recording could be obtained. We recently described the technique of transcutaneous phrenic nerve stimulation in detail [ 3 ] . In short, the left and right phrenic nerves were stimulated percutaneously at the posterior border of the sternocleidomastoid muscles at the level of the upper part of the thyroid cartilage. The diaphragmatic potential was recorded from surface disc electrodes placed over the ipsilateral seventh intercostal space close to the costal margin (7CS) with reference to an electrode over the xiphoid process (XP) or the opposite knee. The graphs were plotted such that the positivity at the 7CS electrode resulted in an upgoing waveform. To ensure exactly the same location of the XP and 7CS recording electrodes for the preoperative and postoperative phrenic studies, distances were measured in each patient between the suprasternal notch and XP electrode and between the XP and the two 7CS electrodes at the time of preoperative assessment. These measurements allowed proper placement of electrodes during the postoperative study when the landmarks were not easily identifiable because of the midsternal incision and the associated superficial edema. A diaphragmatic potential of less than 0.4 mV in amplitude or more than 10 msec in latency was considered abnormal. Also, a leftkight amplitude ratio of the diaphragmatic potential of more than 2.0 or less than 0.5 was considered abnormal. All patients had radiographs of the chest before the operation and at variable intervals (usually three to five times) during the first week after the operation. The presence and location of infiltrates and atelectasis and the position of the hemidiaphragm were noted for each examination. We also obtained the following data: duration of cardiopulmonary bypass, use of topical ice or cold solution for cardiac cooling, lowest myocardial temperature, length of intubation, and duration of hospital stay. Student t and chi-square tests were used for statistical analysis; a p value less than 0.05 was considered statistically significant. During the same study period, an additional 7 patients were evaluated with phrenic studies because they had respiratory difficulty after cardiothoracic surgical procedures.
69 Markand et al: Phrenic Nerve Palsy after Open-Heart Surgery
Results All 50 patients included in the study had preoperative assessment of their phrenic nerve function, but postoperative evaluation could be completed in only 44 patients. Four patients declined postoperative phrenic studies because of discomfort associated with the electrical stimulation of the phrenic nerves during the preoperative evaluation. Two patients could not be restudied because the electrophysiologist (0.N. M.) was not available to perform the test. Thus, data were analyzed for the 44 patients who had both preoperative and postoperative electrophysiological studies. The preoperative radiographs of the chest showed no infiltrate or atelectasis except in 1 patient with subsegmental bibasilar atelectasis that was more extensive on the left side. Postoperatively all patients had three or more studies in the first week after operation. Fortythree patients (98%)showed atelectasis, or infiltrates, or both in one or more of the postoperative radiographs. Changes occurred only in the left base in 13 (30%), whereas 30 (70%) had bilateral changes. In patients with bilateral pulmonary atelectasis, infiltrates, or both, the alterations generally were more severe on the left side. The changes initially occurred on the left side with subsequent development of similar abnormalities on the
right side. The chest radiographs usually showed more severe alterations 2 days after the operation rather than in the immediate postoperative period. In all patients, the amplitude and the latency of the diaphragmatic potential were normal in the preoperative studies. Postoperatively, 5 patients had marked changes in their phrenic studies (Table 1).Patient 1 had the most prominent change; his left phrenic nerve became totally inexcitable. It remained so for four months before the function returned in the last study performed 28 weeks after the operation (Fig 1).In 2 patients (Nos. 3, 4, see Table 1) the left and in 2 (Nos. 2, 5), the right phrenic responses were markedly reduced in amplitude (Fig 2). The 3 patients with abnormal electrical responses to left phrenic stimulation also demonstrated elevation of the left hemidiaphragm on chest radiograph. On the other hand, the 2 patients with right phrenic abnormality on electrical study failed to show radiological findings of hemidiaphragmatic paresis. After the 5 patients with obvious postoperative changes in phrenic nerve function were excluded, the mean values for amplitude and latency of the diaphragmatic potential in the remaining 39 patients in the operative and postoperative studies were compared (Table 2). The latency of the right and left diaphragmatic re-
Table 1. Preoperative and Postoperative Studies in 5 Patients Who Had Substantial Changes in Phrenic Nerzv Conduction Phrenic Nerve Studies Amplitude (mV)
Latency (msec) ~
_
_
_
~
Patient No., Age (yr), Sex
Operation(s)
Time of Study
Right
Left
Right
Left
Comments
1. 54, M
CABG
Preop Postop, Postop, Postop, Postop, Postop, Preop Postop,
0.80 X X X X 0.40 0.60 0.70
7.9 8.6 7.2 7.5 7.3 7.6 6.5 7.4
8.9 X
Extubated on POD 1; infiltrates and pleural effusion in left lower lobe; elevated L hemidiap hragm
2 wk
1.00 0.80 0.75 0.60 0.70 0.80 0.60 0.30
Preop Postop, 1 wk Postop, 2 wk
0.90 0.60 0.60
0.95 0.10 0.20
8.9 8.9 9.6
7.9 8.3 10.5
Preop Postop, Postop, Postop, Postop, Preop Postop, Postop,
0.60 0.60 0.45 0.45 0.45 0.60 0.30 0.26
0.60 0.16 0.12 0.16 0.26 0.90 0.60 0.75
7.9 8.0 7.6 7.4 7.6 6.3 7.2 7.1
8.2 7.7 9.1 9.6 8.5 6.2 6.5 6.3
2. 69, F
3. 70, F
4. 57, F
5. 59, M
MVR
CABG + resection of LV aneurysm AVR + MVR
CABG
CABG = coronary artery bypass grafting; MVR ventricular; POD = postoperative day.
=
1 wk 6 wk 10 wk 15 wk 28 wk
1.5 wk 3 wk 12 wk 22 wk
1 wk 3 wk
X X
X 14.1 6.2 7.0
mitral valve replacement; AVR = aortic valve replacement; X
=
Extubated on POD 2; right-sided atelectasis and infiltrates; bilateral pleural effusion Extubated on POD 1; bilateral atelectasis and infiltrates; bilateral pleural effusion; elevated L hemidiaphragm Extubated on POD 1; bilateral basal atelectasis; elevated L hemidiaphragm
Extubated on POD 1; bilateral basal atelectasis and infiltrates; right-sided pleural effusion no diaphragmatic potential; LV
=
left
70 The Annals of Thoracic Surgery Vol 39 No 1 January 1985
RT PHRENIC N.
L T PHRENIC N.
&*
C
X P ICS
A
I
-
__
~
ID
1 5 0 0 p V
10msec
Fig 1 . Serial phrenic nerve studies in Patient I (see Table 1) (A) one day before coronary bypass and ( B ) 1 , (C) 6 , ( D ) 10, and (€) 28 weeks after the operation. The left phrenic nerve became inexcitable after operation. Function returned in the last study, but the diaphragmatic potential is of lower amplitude and prolonged latency (14.0 rnsec).
sponses showed no major change after the operation. There was a tendency for the amplitude of the diaphragmatic potential to decrease in the postoperative study, but the difference reached statistical significance only for right phrenic stimulation. Following operation, 38 patients (86%)were extubated within a day. Five were extubated 2 days and 1, 4 days after the operation. Of the 5 patients who had marked postoperative alteration of the phrenic nerve study, only Patient 2 needed a longer period (2 days) of assisted ventilation after the operation. Among the 44 patients, 26 had intermittent cold blood potassium cardioplegia without topical myocardial cooling and 18 had topical cooling with either cold saline or ice-slushed saline solution. Phrenic palsy developed in 2 patients from the former group (without topical cooling) and in 3 from the latter (with topical cooling); the difference was not statistically significant. The lowest myocardial temperature recorded in the patients without phrenic palsy was 12.08" f 2.13"Ccompared with 12.24' k 2.11"Cin those with postoperative phrenic palsy. The level of systemic hypothermia was also similar (24" to
10 msec
rnOCC
Fig 2. Phrenic nerve studies in Patient 3 (see Table 1) ( A ) one day before, ( B ) 1 week after, and (C) 2 weeks after coronay arte y bypass and resection of left ventricular aneurysm. Studies show marked reduction in the amplitude of the diaphragmatic potential postoperatively on left phrenic stimulation. (XP = electrode placed over the xiphoid process; 7CS = electrode placed over the ipsilateral seventh intercostal space close to the costal margin; K = electrode placed over the knee.)
25°C) in patients with and without phrenic palsy. Duration of cardiopulmonary bypass was found to be longer in the patients with phrenic palsy: 170.40 k 38.44 minutes versus 126.08 k 33.18 minutes in patients without phrenic palsy. This difference was statistically significant ( p < 0.02). Seven patients were referred for phrenic studies because they could not be weaned off mechanical ventilation or had respiratory difficulties following cardiothoracic operations. These patients were derived from a total of 224 patients who had open-heart procedures Table 2. Preoperative and Postoperative Studies of Diaphragmatic Potential in 39 Patients" Variable Right phrenic nerve stimulation Amplitude (mV) Latency (msec) Left phrenic nerve stimulation Amplitude (mV) Latency (msec)
Preoperahve Study
Postoperative Study
Significance
0.81 C 0.20 7.86 2 0.76
0.71 2 0.20 7.91 t- 0.71
y < 0.05 NS
0.78 2 0.23 7.85 2 0.68b
0.70 0.21 7.92 t- 0.7Ib
*
NS NS
'Values shown are mean f standard deviation. bFor this study, N = 38; in 1 patient, diaphragmatic potential on left phrenic stimulation did not have a good "takeoff" to determine latency accurately.
NS
=
not significant.
71 Markand et al: Phrenic Nerve Palsy after Open-Heart Surgery
Table 3 . Phrenic Nerve Conduction in 7 Patients Who Had Respiratory Difficulties following Cardiothoracic Operations Phrenic Nerve Studies Amplitude Patient No., Age, Sex
Operation(s)
1. 3 mo, Ma
Repair of coarctation
2. 73 yr, Ma
Cholecystectomy, CABG (5 yr previously) Repair of mitral insufficiency
3. 9 mo, F
Interval after Operation
Latency (msec)
(mv)
Right
Left
Right
4d
0.90
X
6d 9 wk 11 wk 7d
X X X 0.80
X X X 1.00
X X X 4.5
X X X 4.0
4.1
Left
Comments
X
Extubated on POD 10; bilateral infiltrates; elevated L hemidiaphragm Patient remained on respirator until his death 3 mo after cholecystectomy Extubated on POD 15; bilateral infiltrates; elevated R diaphragm Extubated on POD 13; bilateral infiltrates; pleural effusion Extubated on POD 1; bilateral infiltrates; elevated L hemidiaphragm Extubated on POD 12; atelectasis and pleural effusion in left lower lobe
4. 4 yr, F
Repair of AV canal
8d
0.55
0.40
4.3
4.4
5. 4 yr, F
Repair of atrial septa1 defect
4d
0.55
0.60
4.9
4.9
6. 71 yr, F”
CABG
0.18 0.20 0.20 0.36 0.40 0.45
X X
8.5 8.7 8.5 7.3 7.3 10.0
X X X 13.5 9.4 9.5
7. 63 yr, M
CABG
12 d 2.5 wk 8 wk 12 wk 20 wk 7d
X 0.16 0.44 0.65
Extubated on POD 3; atelectasis of left lower lobe; bilateral pleural effusion
“Patient had abnormal phrenic nerve studies.
CABG = coronary artery bypass grafting; AV
=
atrioventricular; X
=
no diaphragmatic potential; POD
during the study period but were not included in the prospective study. They did not have preoperative assessment of phrenic nerve function. Electrical stimulation of their phrenic nerves demonstrated evidence of unilateral diaphragmatic paralysis in 1 and bilateral dysfunction in 2 of these patients; phrenic study results were normal in the remaining 4 patients (Table 3). One patient (No. 2; see Table 3) studied a week after removal of the gallbladder for acute cholecystitis, showed inexcitable phrenic nerves bilaterally. Two additional studies over the succeeding three months also failed to evoke a response even on intense stimulation of his phrenic nerves. This patient had undergone coronary artery bypass grafting five years previously when a left phrenic paralysis developed; his chest radiograph before the gallbladder operation showed an elevated left hemidiaphragm. Damage to the diaphragm itself or to the phrenic nerve during cholecystectomy resulted in bilateral inexcitable phrenic nerves that required artificial ventilation until the patient’s death three months after the gallbladder operation. In a 3-month-old child (Patient 1; see Table 3) the left phrenic nerve was found to be inexcitable following repair of coarctation of the aorta, but a normal diaphrag-
=
postoperative day
matic response was recorded on the other side. In the remaining patient (No. 6; see Table 3) who had coronary artery bypass grafting, inexcitable left phrenic nerves were associated with a reduced response on right-sided stimulation. Serial studies in this patient demonstrated a partial return of function by twelve weeks and almost normal function by twenty weeks after the operation. The phrenic latency gradually decreased as the diaphragmatic potential attained normal amplitude. All 7 patients had pulmonary atelectasis, or infiltrates, or both, often bilaterally, and the changes were not appreciably different in the patients with or without abnormal phrenic nerve conduction studies. Three patients with abnormal phrenic nerve studies had radiographic evidence of diaphragmatic paralysis on the ipsilateral side. Two patients (Nos. 3, 5; see Table 3) were suspected of having diaphragmatic paralysis on radiological grounds but had normal and symmetrical responses on phrenic nerve stimulation.
Comment Infiltrates or atelectasis or both developed in the left lower lobe of 98% (43 of 44) of patients with or without a similar involvement of the right lower lobe in the im-
72 The Annals of Thoracic Surgery Vol 39 No 1 January 1985
mediate postoperative period. These findings are similar to the observations of Good and colleagues [l]and Benjamin and associates [2], who reported an incidence of more than 85% for similar complications following coronary artery bypass. Three causes have been proposed for such a high incidence of postoperative pulmonary complications: (1)gastric distention following operation with elevation of the hemidiaphragm, (2) damage to the phrenic nerves as a result of direct surgical trauma or from topical hypothermia secondary to ice cooling of the heart, and (3) trauma to the lung, particularly the left lower lobe secondary to retraction during operation. The role of gastric distention can be virtually eliminated because nasogastric tubes inserted before the operation failed to prevent pulmonary complications. Mechanisms similar to the postoperative atelectasis observed in upper abdominal operations are also not responsible, as the routine use of positive end-expiratory pressure has been found to be ineffective in preventing pulmonary complications following coronary artery bypass grafting [l]. Transient paralysis of the left phrenic nerve resulting from hypothermic injury secondary to ice cooling of the heart has been strongly supported by evidence from Benjamin and co-workers [2]. They reported left lower lobe infiltrates and atelectasis in 63 to 85% of their patients who underwent operation with topical cooling of the heart using ice compared with an incidence of 32.5% in patients without such intraoperative cooling. These authors found a high incidence (69.2%)of abnormal diaphragmatic motion in the chest radiographs of patients with left lower lobe abnormality, but they did not carry out electrophysiological studies of the phrenic nerves. That transient phrenic nerve dysfunction can develop secondary to hypothermic injury has been shown experimentally by Marco and colleagues [4], who found that application of ice to the phrenic nerves of dogs for 30 to 60 minutes resulted in paralysis lasting one to four weeks. Whether this paralysis is the sole mechanism for the almost invariable development of infiltrates and atelectasis observed after open-heart operations in human beings, however, can be questioned on several grounds. First, a high incidence of pulmonary complications following open-heart surgery has been reported, even when ice cooling of the heart was not carried out. In our series all but 1 of the patients had these postoperative complications. Second, we and other groups [l] have shown that the incidence of atelectasis and infiltrates is higher 2 or more days following rather than immediately after operation, a finding that would be difficult to explain if the changes were due to hypothermic phrenic nerve injury sustained during the operation. Third, our electrophysiological evaluation of phrenic nerve-diaphragm function assessed in patients before and after open-heart procedures established that 89% (39/44) of the patients had no marked changes in phrenic nerve conduction following operation. We think that trauma to the lungs secondary to retraction and subsequent pulmonary contusion is probably
the most common cause for the high incidence of pulmonary complications seen in the immediate postoperative period following open-heart surgical procedures. Decreased ability to cough secondary to chest pain and sedation with resultant retained secretions may be additional causative factors. The more common and severe involvement of the left side probably reflects more severe operative trauma due to the retraction of the left lung. There is also an increasing body of evidence that microaggregates of platelets, fibrin, and leukocytes lodging in the pulmonary vasculature during extracorporeal circulation may contribute to pulmonary complications after open-heart surgery [5]. Undoubtedly a small proportion of patients do sustain phrenic nerve damage during cardiothoracic operations; the incidence of this complication was 11%(5 of 44 patients) in our prospective study. The incidence of total phrenic paralysis, however, was lower: only 1 of the 44 had total lack of response on stimulation of the left phrenic nerve after the operation. Three other patients with total phrenic nerve paralysis were identified among 224 open-heart operations conducted during the same study period-an incidence of approximately 1.5%. Others [6-81 have reported a similar incidence of this complication following cardiothoracic operations. We think that phrenic nerve damage is primarily a stretch injury, which may occur during retraction of the sternum or prolonged pericardial stretch applied through weights during the operation. Although the use of topical cardiac cooling or the lowest myocardial temperature during operation had no major influence when considered individually, hypothermic injury may play an important additive role in causing phrenic palsy. Longer duration of cardiopulmonary bypass in patients in whom phrenic palsy developed would support the notion that longer duration of stretch and prolonged systemic hypothermia may be crucial etiological factors. Reducing the duration of both the systemic hypothermia and the pericardial stretch during operation may help reduce the incidence of intraoperative phrenic injury. The present investigation had one notable limitation in that the electrophysiological evaluation was performed at least 6 days after the operation because of the technical difficulties in the immediate postoperative period. It is therefore possible that we may have missed cases of transient postoperative diaphragmatic dysfunction, which might have recovered by the time of the electrical evaluation. Nonetheless, our investigation strongly suggests that diaphragmatic paresis of a clinically significant degree occurs in a much smaller percentage of patients after open-heart procedures than the incidence of postoperative pulmonary complications would dictate. We found no change in the latency but a slight decrease (10%) in the mean amplitude of the diaphragmatic potential following open-heart operation (see Table 2). The change, which was slightly greater for the right-sided stimulation, remains unexplained. It may be due to increased tissue impedance secondary to postop-
73 Markand et al: Phrenic Nerve Palsy after Open-Heart Surgery
erative alterations in the intrathoracic and superficial tissues. The effect of phrenic nerve palsy on the mechanics of respiration varies according to the status of other respiratory muscles and associated pulmonary complications. Unilateral phrenic nerve palsy in the presence of pulmonary infiltrates or effusion may compromise ventilation to the extent that prolonged ventilatory support is required, as was the case in 3 of our 4 patients who had total paralysis of the diaphragm on one or both sides. The only patient with bilateral inexcitable phrenic nerves required mechanical ventilation until his death. Stephens [6] reported that compared with older children, infants with unilateral phrenic paralysis did less well in the immediate postoperative period because they more commonly required prolonged ventilatory support and, rarely, diaphragmatic plication. The long-term outcome of unilateral phrenic paralysis, even when complete, appears to be favorable, at least in adults, because all of the patients in our series attained normal ventilatory status after 2 to 3 weeks. The stretch injury to the phrenic nerve is mainly to the axons, and the integrity of the nerve remains largely intact; hence, recovery may be expected. The time taken for recovery depends on the site of injury and the rate of regeneration. When the phrenic nerve was crushed in the neck as a therapeutic procedure to treat tuberculosis, the majority of patients had return of diaphragmatic motion over the following six months [9]. Similar nerve injury in the thorax is expected to take a shorter period for recovery. Three of our 4 patients who had follow-up studies extending beyond ten weeks of the operation showed evidence of recovery of the phrenic nerve function; the recovery time appears to be between three and six months. In the past phrenic nerve paralysis has been detected largely by radiological investigations. Electrophysiological assessment of the phrenic nerve function has been mentioned only rarely in patients who experienced phrenic paralysis following cardiothoracic operations [lo-121. An elevated hemidiaphragm in radiographs of the chest with atelectasis and infiltrates of the lower lobe on that side is suggestive of unilateral phrenic paralysis, but local pulmonary pathology, eventration of the diaphragm, or infradiaphragmatic disease may produce similar findings. A fluoroscopic examination of the chest that demonstrates reduced excursion of the hemidiaphragm and paradoxical motion is considered diagnostic of diaphragmatic paralysis, although fluoroscopy may be delayed because of the condition of the patient. The findings also may be difficult to interpret, particularly in the presence of pleural effusion or atelectasis. Un-
equivocal evidence of phrenic nerve damage, on the other hand, can be quickly established by percutaneous phrenic nerve stimulation. The technique is easy, can be performed at the bedside of the patient, and can be repeated as often as desired. Serial studies may also provide the earliest evidence of return of phrenic nerve function. Therefore, electrophysiological evaluation of phrenic nerves should be included in the assessment of patients who have ventilatory difficulties, pulmonary atelectasis and infiltrates, and elevation of hemidiaphragm in the postoperative period following cardiothoracic surgical procedures. We thank the cardiovascular surgical house staff for their cooperation in obtaining preoperative and postoperative phrenic nerve studies on patients in their care. We also thank Mrs. Martha Stanley for typing the manuscript.
References 1. Good JT Jr, Wolz JF, Andersen JT, et al: The routine use of positive end-expiratory pressure after open heart surgery. Chest 76~397,1979 2. Benjamin JJ, Cascade PN, Rubenfire M, et al: Left lower lobe atelectasis and consolidation following cardiac surgery: the effect of topical cooling on the phrenic nerve. Radiology 142:11, 1982 3. Markand ON, Kincaid JC, Pourmand RA, et al: Electrophysiologic evaluation of diaphragm by transcutaneous phrenic nerve stimulation. Neurology 34:604, 1984 4. Marco JD, Hahn JW, Barner HB: Topical cardiac hypothermia and phrenic nerve injury. Ann Thorac Surg 23235, 1977 5. Ratliff NB, Young WG Jr, Hackel DB, et al: Pulmonary injury secondary to extracorporeal circulation. J Thorac Cardiovasc Surg 65:425, 1973 6. Stephens JW: Neurological sequelae of congenital heart surgery. Arch Neurol 7450, 1962 7. Mickell JJ, Oh KS, Siewers RD, et al: Clinical implications of postoperative unilateral phrenic nerve paralysis. J Thorac Cardiovasc Surg 76297, 1978 8. Lederman RJ, Breuer AC, Hanson JR, et al: Peripheral nervous system complication of coronary artery bypass graft surgery. Ann Neurol 12:297, 1982 9. Iverson LI, Mittal A, Dugan DJ, et al: Injuries to the phrenic nerve resulting in diaphragmatic paralysis with special reference to stretch trauma. Am J Surg 132:263, 1976 10. Davis JN: Phrenic nerve conduction in man. J Neurol Neurosurg Psychiatry 30:420, 1967 11. Shaw RK, Glenn WWL, Hogan JF, Phelps ML: Electrophysiological evaluation of phrenic nerve function in candidates for diaphragm pacing. J Neurosurg 53345, 1980 12. Moosa A: Phrenic nerve conduction in children. Dev Med Child Neurol 23:434, 1981