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Eur J Cardiothorac Surg 2003;23:384-389
© 2003 Elsevier Science NL

Factors associated with cardiac rhythm disturbances in the early post-pneumonectomy period: a study on 259 pneumonectomies

Second Department of General Thoracic Surgery, Athens Chest Diseases Hospital ‘Sotiria’, Athens, Greece

Received 6 August 2002; received in revised form 20 November 2002; accepted 25 November 2002.

^* Corresponding author. 35 Ioustinianou Street, 41223 Larissa, Greece. Tel.: +30-241-028-7466; fax: +30-241-061-1097
e-mail: foroulis{at}internet.gr

	Abstract

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
Objective: To identify predisposing factors associated with cardiac rhythm disturbances during the early post-pneumonectomy period (first 7 postoperative days). Materials and methods: During the study period (1995–1999), 259 pneumonectomies were performed for malignant (244 cases) or benign disease (15 cases). Postoperative monitoring of patients included continuous arterial pressure - rhythm monitoring and pulse oximetry. Cardiac rhythm disturbances during the intensive care unit stay were detected on the monitor screen and recorded with a 12-lead electrocardiogram. Cardiac rhythm disturbances associated with electrolytes or fluid balance abnormality, mediastinal deviation or surgical postoperative complications were excluded from the study. Age of patients, preexisting cardiac disease, side of pneumonectomy, intrapericardial procedures, stage of the malignant disease, expected postoperative FEV₁<1200 ml, intraoperative transfusions of packed red cells, elevated right heart pressures, low postoperative serum magnesium levels and long operative times were considered as predisposing factors for the development of post-pneumonectomy cardiac rhythm disturbances. Statistical analysis has been made using logistic regression analysis, Student t-test and chi-square test. Results: Cardiac rhythm disturbances were detected in 49 patients (18.91%). Atrial fibrillation/flutter (31 cases), supraventricular tachycardia (14 cases), and premature ventricular contractions (four cases) were the observed rhythm disturbances. Right pneumonectomy versus left pneumonectomy (P<0.0001) and intrapericardial pneumonectomy versus standard pneumonectomy (P<0.0001) were identified as strong predisposing factors for the establishment of post-pneumonectomy cardiac rhythm disturbances. Patients who established post-pneumonectomy cardiac rhythm disturbances had significantly higher (P=0.024) right ventricular systolic pressure (42.50±15.50 mmHg) when compared with patients who had postoperative sinus rhythm (29.07±7.71 mmHg) and had also longer operative times than patients who did not develop rhythm disturbances (P=0.015). Mortality rate in patients who developed post-pneumonectomy rhythm disturbances was 20.40%. Conclusions: Cardiac rhythm disturbances observed early after pneumonectomy are mainly of supraventricular origin, complicating right and intrapericardial pneumonectomies, patients with elevated right heart pressures and long operative times, and are associated with high mortality rates.

Key Words: Pneumonectomy • Post-pneumonectomy complications • Post-pneumonectomy cardiac arrhythmia • Post-pneumonectomy cardiac dysrhythmia • Post-pneumonectomy cardiac rhythm disturbance

	1. Introduction

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
Pneumonectomy is a serious operation, associated with a high rate of postoperative morbidity (15–75%) and mortality (4.8–18%) [1–3]. Cardiac rhythm disturbances (CRDs) are well-documented post-pneumonectomy complications, of great importance, and necessitating closed observation of the patient for recognition and application of the appropriate therapy, in order to avoid reduction of the cardiac output and subsequent ischemia of heart, brain and kidneys [1–6]. In our retrospective study, we try to estimate the incidence of post-pneumonectomy CRDs and to identify independent risk factors predisposing to CRDs after pneumonectomy.

	2. Patients and methods

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
2.1. Patients and operative technique
The study is retrospective and the medical records of 259 patients who underwent elective pneumonectomy from June 1995 to June 1999 (4 years) were reviewed. Completion pneumonectomies were not included in the study. Pneumonectomy was performed for lung cancer in 244 cases (94.20%) and for benign disease in 5.80% (tuberculosis in 14 cases and invasive aspergillosis in one); 223 patients were male and 36 female and the mean age was 65.26±5.51 years. The preoperative Karnofsky score of performance status varied from 90 to 100% in almost all patients, with the exception of seven patients, where the preoperative Karnofsky scale was 70% due to the presence of Eaton–Lambert syndrome. General anesthesia with propofol, remifentanil, sis-atracurium and one-lung ventilation, using left-sided double lumen endotracheal tubes, were applied in all patients. All patients were extubated in the operating room or in the intensive care unit (ICU), within the first 6 h postoperative period. Extrapleural pneumonectomies were performed in ten cases for a lung destroyed from tuberculosis. Left extrapleural intrapericardial pneumonectomy was performed in one case for scar adenocarcinoma of the left upper lobe, located on a lung destroyed from tuberculosis. Atrial resections were performed in seven cases where the tumor extended via the pulmonary veins and invaded the left atrium. Pericardial defect repair in cases of intrapericardial pneumonectomy has been made using mersilene mesh patch in 19 cases or using a pedicled parietal pleural flap in seven cases. Simple reapproximation of the pericardial edges (without tension) has been obtained in 28 cases, while in the remaining 35 cases the pericardium was left open (small pericardial defects around the pulmonary artery stump). En bloc chest wall and lung resections were performed in nine cases, because of chest wall invasion. In every case of pneumonectomy for primary lung cancer, formal mediastinal lymph node dissection accomplished the operation (lymph node stations 2, 3, 4, 7, 8, 9 on the right side and stations 3, 5, 7, 8, 9 on the left side). A standard posterolateral thoracotomy was used in all patients. Underwater seal drainage of the post-pneumonectomy space was routinely performed. Chest tubes were appropriately clamped, except to monitor or readjust pleural pressures. Normally, chest tubes were removed within 48 h after surgery.

2.2. Patient monitoring
All patients who underwent pneumonectomy had a minimal of 24 h ICU stay (mean stay: 39.08±19.63 h, range: 24–120 h). Postoperative monitoring of post-pneumonectomy patients included continuous monitoring of blood pressure (BP) via a radial artery catheter, continuous monitoring of heart rate (HR) on the monitor screen, pulse oximetry and hourly urine output. Central venous pressure (CVP) via a subclavian vein catheter was obtained manually at least twice daily. Arterial blood gases determination, serum potassium/sodium/calcium concentration and serum hemoglobin levels were obtained twice daily (heparinized blood samples via the radial artery catheter) and were analyzed in the Ciba-Corning 288 blood gas analyzer (Ciba-Corning Prognostics Group, USA) as the standard postoperative hematological and biochemical monitoring of patients. When CRDs were seen in the monitor screen, a full 12-lead electrocardiogram was taken for the exact demonstration of the arrhythmia. All patients had standard portable chest roentgenogram at the arrival at ICU, the day after surgery, after removal of chest tube and before discharge from the hospital. Additional chest roentgenograms were applied when necessary. Upon transfer of post-pneumonectomy patients to the ward, manually obtained arterial pressure and pulse rate measurement was performed in all patients every 4 h. Additionally, pulse oximetry and telemetric monitoring of the heart rate/rhythm were applied individually, as needed.

2.3. Arrhythmias: exclusion criteria
All the observed CRDs during the early post-pneumonectomy period (first seven postoperative days) were collected and reviewed from patient medical records [3]. CRDs associated at their onset with potassium concentration lower than 3.6 mEq/l or fluid balance and acid–base abnormalities or mediastinal deviation, were excluded from the study protocol. Patients who developed surgical postoperative complications (early bronchopleural fistula formation in two cases, cardiac tamponade or pre-tamponade in two cases, cardiac herniation in one case) and four patients who underwent postoperatively therapeutic mechanical ventilatory support were also excluded from the study. In the other hand, CRDs observed during ICU stay of six patients who underwent chest reopening for bleeding (not massive) during the first 24 postoperative hours were included in the study. Two patients who had chronic atrial fibrillation were also excluded from the study. The management of each detected CRD was also noted during the review of medical records.

2.4. Perioperative and postoperative management
Preoperative prophylactic administration of digitalis was not a routine in the candidates for pneumonectomy patients. Digoxin (0.5 mg i.v. given as a standard dose) was administered to all patients who underwent right or intrapericardial pneumonectomy and in patients who received preoperatively digitalis for medical reasons (eight patients) at their arrival at ICU, if no contraindication existed. All patients received low molecular weight heparin for prophylaxis against deep venous thrombosis (Nadroparin calcium 5700 anti-Xa IU s.c. once daily). Standard postoperative parenteral fluid administration in our post-pneumonectomy patients was 1000–1500 ml of dextrose solution 5% from the end of surgery and transport of the patient to the ICU until the morning of the first postoperative day. Additional fluid administration was made individually according to the blood pressure, heart rate and central venous pressure of patients. Oral fluid administration started normally the morning after surgery and every attempt was made to stop as soon was possible any parenteral fluid administration. Packed red cell transfusions were given if hemoglobin dropped to levels less than 9 mg/dl. Postoperative analgesia was achieved with the administration of morphine sulfate (7.5 mg every 6 h subcutaneously) plus the administration of diclofenac suppositories (50 mg every 12 h).

2.5. Study design and statistical analysis
Predictor factors for the development of post-pneumonectomy CRDs were considered as follows:

Patients >65 versus patients <65 years old.

Patients with preexisting cardiac disease (Q wave myocardial infarction in 14 patients, ventricular or atrial extrasystoles well-controlled by anti-arrhythmic agents in 11 patients (propaphenone hydrochloride), mild aortic or mitral valvular disease not requiring surgery at the time of thoracotomy in 20 patients, arterial hypertension associated with left ventricular hypertrophy well-controlled by one drug or combination of drugs in 19 patients) versus patients with preoperatively normal heart function, according to the medical history, clinical examination, and preoperative electrocardiogram (standard preoperative examination) or Doppler echocardiography and electrocardiogram stress test, when they were performed.

Right pneumonectomy versus left pneumonectomy.

Intrapericardial versus standard pneumonectomy.

Pneumonectomy for malignant versus pneumonectomy for benign disease.

Patients with pathologic TNM stage II versus patients with pathologic stage IIIA lung cancer.

Patients who had expected postoperative forced expiratory volume in 1 s (FEV₁) <1200 ml, according to the preoperative spirometry results and the preoperative perfusion lung scan (performed in all patients with an preoperative FEV₁<2000 ml) versus patients with expected postoperative FEV₁ more than 1200 ml (preoperative FEV₁/2>1200 ml).

Patients who received intraoperatively red packed cell transfusions versus patients who did not receive transfusions. Fifteen patients (5.79%) received red packed cell transfusions intraoperatively (mean: 3.00±1.06 units, range: 2–5 units), because of prolonged operations (two cases), extrapleural pneumonectomies (ten cases) or intraoperative significant blood loss (two patients).

Difference in percentage of patients who postoperatively developed CRDs or not between the above-described subgroups is presented in Table 1, while logistic regression analysis was used in order to find independent predictor factors which had strong impact on CRDs development.

Postoperative serum magnesium levels were considered also as possible predisposing factors for post-pneumonectomy dysrhythmias development and were measured in 30 patients of the study before surgery, at their arrival at ICU, the day after surgery and on the second postoperative day. Comparison of serum magnesium levels between patients who postoperatively developed CRDs or not, was made using the Student t-test.

Thirty-seven patients in the study underwent Doppler echocardiographic study of the heart on day 30 after surgery, measuring right ventricular systolic pressure (RVSP) by using the maximal tricuspid regurgitation Doppler jet velocity (V_max) and the modified equation proposed by Currie et al. (RVSP=4V_max2+10 mmHg) [7]. The mean RVSP of patients who developed post-pneumonectomy CRDs and patients who had postoperatively sinus rhythm were compared using the Student t-test.

P-values of less than 0.05 were considered significant and statistical analysis was made using the software SPSS version 9.0 for windows.

	3. Results

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
CRDs were detected in 49 patients (18.91%). Atrial fibrillation in 25 cases (51.02%), atrial flutter in six cases (12.24%), supraventricular tachycardia in 14 cases (28.57%), and frequent premature ventricular contractions in four cases (8.16%) were the observed postoperative CRDs. The observed CRDs were of supraventricular origin in 91.83% of cases. All the detected CRDs were generated within 96 h after surgery and were immediately detected after their onset on the monitor screen.

Right pneumonectomy and intrapericardial pneumonectomy were identified by logistic regression analysis as strong predisposing factors for the establishment of postoperative CRDs. (coefficient values: -1.1275 and -0.8053, respectively, and corresponding odds ratio estimates: 0.324 and 0.447, respectively).

The mean hematocrit value (at ICU arrival) of patients who established CRDs (31,44±2.55%) had no difference (t-test: P=0.104) to the mean hematocrit value of patients who had sinus rhythm postoperatively (30.40±2.09%). The mean operative time of patients who developed postoperative CRDs (207.02±70.39 min) was significantly longer (t-test: P=0.015) than patients who did not develop CRDs postoperatively (181.41±20.85 min).

CRDs were observed in three out of the 30 patients (10%) where serum magnesium levels were measured. No statistical difference concerning serum magnesium levels was observed between patients who developed preoperatively CRDs or not, at the arrival at ICU, the day after surgery and on the second postoperative day (Table 2).

Drug therapy was necessary in all 49 patients to succeed conversion to sinus rhythm and to prevent complications. Atrial fibrillation was initially managed by the intravenous administration of digoxin (0.5 mg i.v. given as a bolus dose within 3 min). If the attempt to convert to sinus rhythm by digoxin was ineffective or digoxin was administered at the arrival at ICU as described previously (21 out of 25 patients who developed atrial fibrillation), intravenous administration of amioadarone was the next step in the management of atrial fibrillation (300 mg diluted in 100 ml of isotonic dextrose solution administered within 30 min (4 mg/kg of body weight)). In three cases atrial fibrillation was resistant to drug therapy, complicating heart failure and resulting hemodynamic deterioration, low cardiac output and death of the patient. Supraventricular tachycardia was initially managed by intravenous administration of digitalis (0.5 mg i.v. as a bolus dose) followed by intravenous administration of verapamil (10 mg i.v. administered in 5 min (0.15mg/kg of body weight)). Therapy was successful in all cases. Premature ventricular contractions were successfully controlled by intravenous lidocaine infusion (60–80 mg bolus infusion (1 mg/kg of body weight), followed by continuous intravenous infusion 1–4 mg/min). In five cases, where the onset of the CRDs (supraventricular tachycardia) was observed intraoperatively and immediately after the application of the atrial clamp, the initial management was the temporary withdrawal of the clamp, resulting in conversion of the tachyarrhythmia to sinus rhythm. Reapplication of the clamp distally to the initial application site a few minutes later was uncomplicated in all cases. CRDs were reestablished in all of these five patients during their ICU stay.

The overall mortality rate during hospitalization in these series was 6.56% (17 out of 259 patients). Mortality rate during hospitalization of patients who developed postoperatively CRDs was 20.40% (ten out of 49 patients). The causes of death were heart failure in four cases, non-occlusive mesenteric ischemia in one (found at laparotomy), respiratory failure in two and multiple organ failure in three. Ischemic complications in relation to CRDs were observed in only one patient, who underwent laparotomy and resection of the ischemic distal ileus and large bowel, due to mild hypotension (80–90 mmHg), as the result of a high rate supraventricular tachycardia (160 beats/min). Mortality rate in patients who did not develop postoperative CRDs was 3.3% (seven out of 210 patients). The difference in mortality rates between patients who developed CRDs or not postoperatively was significant (chi-square test: P<0.01).

	4. Discussion

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
The high incidence of CRDs after pulmonary parenchyma resection was reported by Currens et al. in the early 1940s [8]. CRDs are nowadays the most common complication of pneumonectomy during the early postoperative period and their incidence has been reported to vary between 11 and 28% [8–15] (Table 3). The observed rate of post-pneumonectomy CRDs during the early post-pneumonectomy period in the present study was 18.91%, representing the commonest detected post-pneumonectomy complication in our practice. Atrial arrhythmias are far more common than ventricular arrhythmias, consisting of atrial fibrillation and flutter and supraventricular tachycardia [1–7]. Atrial fibrillation is reported to be the most frequent CRD in post-pulmonary parenchyma resection patients (63–85%) and supraventricular tachycardia follows with a reported incidence from 13 to 26% [6,8]. Ninety-two percent of the observed CRDs in the present study were of supraventricular origin.

Refractory to treatment or recurrent CRDs are associated with devastating mortality rates (69%), as reported by Krowka et al. [12]. The three patients of the present study, who had a refractory to treatment CRD, died during hospitalization because of hemodynamic deterioration. High mortality rates in patients who develop CRDs during the post-pneumonectomy period still remain unchanged over time, despite improvements in surgical technique, postoperative care and the development of ICU in almost every hospital where general thoracic surgery practice is performed. CRDs are not the direct cause of death of post-pneumonectomy patients, with the exception of CRDs complicating heart failure or resulting prolonged hypotension. Early detection of the arrhythmia may improve outcome in elderly patients, where even transient hypotension is not well tolerated. We had one case of non-occlusive mesenteric ischemia and bowel necrosis in our series, due to supraventricular tachycardia resulting in mild hypotension.

Many causes have been proposed to explain the high incidence of CRDs during the early post-pneumonectomy period. Hypoxemia, vagal irritation, atrial inflammation, preexisting cardiac disease, pulmonary hypertension and right heart dysfunction have been considered as possible, but not yet validated, causes of CRDs [1–6]. Penfield Faber and Piccione report that patients who are at high risk to experience post-pneumonectomy CRD cannot be accurately identified at the moment [5]. Well-documented factors associated with CRDs are reported in the literature to be age greater than 65–70 years old, right and intrapericardial pneumonectomy, preexisting cardiac disease, and postoperative interstitial pulmonary edema [1–6,12]. The results of the present study support that right and intrapericardial pneumonectomy are strong predisposing factors for the development of post-pneumonectomy CRDs. Amar et al. supported that the extent of resection plays an important role in the generation of CRDs after pulmonary parenchyma resection, mainly after extrapleural pneumonectomy for pleural mesothelioma (40% incidence of postoperative CRDs) [6]. The higher incidence of postoperative CRDs after right pneumonectomy than after left pneumonectomy may be attributed to the larger amount of pulmonary parenchyma resected.

According to the results of the study by Krowka et al., age and TNM stage had no predictive value in determining patients at high risk for the development of post-pneumonectomy CRDs [12]. Our results agree with the results reported by Krowka et al., as the observed rate of post-pneumonectomy CRDs had no difference between patients older than 65 years and younger patients and in patients with pathologic stage II and IIIA lung cancer. A serious observation of the present study is that post-pneumonectomy CRDs were associated with elevated right heart pressures. Acute critical decrease of the pulmonary vascular bed is a major contributing factor in the establishment of post-pneumonectomy CRDs, as also supported by Amar et al. [6,16].

The high incidence of CRDs after intrapericardial pneumonectomy is well documented, but no certain explanation exists for the event [1–6]. In our opinion, pericardial irritation and inflammation, possible partial protrusion of the right or left atrial appendage through a non-repaired superior pericardial gap, accumulation of different amounts of fluid into the pericardial sac during different positions of the patient body, and irritation of the heart produced by chest tube could explain the high incidence of CRDs after intrapericardial procedures. None of the above-mentioned situations is proven at the moment and only observations made during early reopening of the chest for other events could support them.

Prophylactic digitalization of all patients has been widely discussed in the past as a prophylactic tool against the generation of post-pneumonectomy CRDs [1–6]. One study showed decreased incidence of post-pneumonectomy CRDs following prophylactic digitalis administration, mainly in older patients [10]. The toxic effect of digitalis and the difficulty in assessing adequate digitalization in patients with normal heart function are the principal arguments against prophylactic digitalization [2]. Amar et al., in a recent randomized study, found diltiazem to be more effective in preventing the overall incidence of post-pneumonectomy CRDs, when compared with digitalis. The incidence of CRDs in their control group had no differences when compared with the group of patients who received digitalis as prophylaxis against the development of postoperative CRDs [16]. In our practice, administration of digitalis started at the arrival in the ICU, in patients who underwent right or intrapericardial pneumonectomy. Retrospectively, we found no certain benefit from this practice, as the incidence of CRDs was similar to that reported in series where prophylaxis was not applied, and we recently abandoned prophylactic use of digitalis in all patients.

Digitalis administration was the initial drug therapy in all cases of atrial fibrillation or supraventricular tachycardia. Calcium-channel blockers and amioadorone were the drugs of choice in cases of resistant or recurrent atrial tachyarrhythmias. Drug therapy was unsuccessful in three cases of postoperative heart failure with fatal outcome. In the past, digitalis and quinidine were effective in the management of atrial tachyarrhythmias, before the onset of calcium-channel blockers and amiodarone [1–3].

In conclusion, CRDs occur with increased frequency in patients undergoing right or intrapericardial pneumonectomies and in patients with increased postoperative right ventricular systolic pressure (35 mmHg). Longer operative times were also associated with increased frequency of postoperative CRDs in the present study. Post-pneumonectomy CRDs are mainly of supraventricular origin and are associated with high mortality rates. Continuous postoperative monitoring of heart rhythm is necessary for early recognition of any CRD. Appropriate drug administration is important in order to avoid cardiac output reduction and sequential ischemia and failure of vital organs. Digitalis, amiodarone and calcium channel blockers are effective drugs in the management of the majority of post-pneumonectomy supraventricular CRDs.

	Acknowledgments

 
The authors would like to thank the Statistician Yannis Bassiakos (Associate Professor, School of Economics, Athens University) for his assistance in statistical analysis of the data.

	Footnotes

 
Presented at the 16th Annual Meeting of the European Association for Cardio-thoracic Surgery, Monte Carlo, Monaco, September 22–25, 2002.

	References

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 

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This Article Abstract Full Text (PDF) 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): Christophoros Kotoulas Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Foroulis, C. N. Articles by Lioulias, A. G. Search for Related Content PubMed PubMed Citation Articles by Foroulis, C. N. Articles by Lioulias, A. G. Related Collections Lung - other