Methods: A retrospective review of consecutive patients undergoing open lobectomy and bilobectomy for primary NSCLC between January 2010 and June 2016 was performed. Patient were divided into those receiving intraoperative IV fluid less than 7 cc/ kg/hr, 7 to 10 cc/kg/hr, and equal to or greater than 10 cc/kg/hr. Postoperative IV fluid was also recorded. We compared this against patient’s demographics, intraoperative parameters and complication rate.
Results: 142 patients with the mean age of 66.5 years were identified. There was no significant difference in the hospital or ICU stay between any of the groups. Patients who received greater than 10 cc/kg/hr intraoperative IV fluids have higher rate of one or more complications and reoperation rate. Patients who had greater than 1.5 cc/kg/hr perioperative fluid have significantly higher duration of chest tube in-situ and pulmonary complication rate. Patients receiving less than 7 cc/kg/hr intraoperative IV fluids have no benefits compare to the group receiving larger IV fluid.
Conclusions: In our study, giving high amounts of intraoperative and perioperative IV fluid has adverse effects on postoperative complications. Giving less (< 7 cc/kg/hr) intraoperative IV fluid has no additional benefits. We propose the optimal amount of intraoperative and perioperative IV fluid given should be in between these two extremes.
Keywords: Lung resection; Non-small cell lung cancer Outcomes; Perioperative fluids
In this study, we investigated outcome measures associated with patients undergoing lung resection for NSCLC and the correlation with volume of perioperative IV fluids.
Preoperative evaluation included a complete history and physical examination, full blood count, biochemical profile and computed tomographic (CT) scan of chest. Pulmonary function test was also performed for majority of the patients. Patient who had a history of or major risk for cardiovascular disease underwent cardiologic evaluation. Relevant comorbidities, tobacco, and alcohol abuse were identified. Alcohol abuse was defined by consumption of hard liquor more than 2 ounces, or beer more than two of 12 oz. cans, or wine more than two 6 oz. glasses per day more than 5 times a week.
All patients had a radial arterial catheter for hemodynamic management and ureteral catheter for accurate urine output measurement perioperatively. Preoperative antibiotics and chemical deep venous thrombosis (DVT) prophylaxis were given. Patients were intubated with a double-lumen endotracheal tube and the operative lung was deflated during the surgery to facilitate dissection. Lung resections were performed with systemic lymph node dissection through a full posterolateral or lateral muscle sparing thoracotomy. Patients were extubated in the operating room or in the recovery area immediately after the transfer if there was no respiratory concern. All patients were monitored in the surgical intensive care unit (ICU) post operatively for at least 24 hours.
The primary exposure investigated in this study was volume of intraoperative and perioperative IV fluids, in cc/kg/hr. Intraoperative IV fluids were defined as only those fluids given in the operating room. Perioperative IV fluids were defined as intraoperative IV fluids and postoperative IV fluid within 24 hours from surgery. This did not include oral fluid intake. For intraoperative fluids, patients were divided into three groups; restrictive (those receiving intraoperative IV fluid less than 7 cc/kg/hr), typical (those receiving 7 to 10 cc/kg/hr), and liberal (those receiving equal to or greater than 10 cc/kg/hr). For perioperative fluids, patients were categorized into high fluids group (those receiving greater than 1.5 cc/kg/hr) or low fluids group (less than 1.5 cc/kg/hr).
The primary outcomes investigated in this study were duration of hospital and ICU stay, length of chest tube in situ, and complications within 30 days of surgery. Complications were categorized as pulmonary, cardiovascular, and renal in etiology. Major hemorrhage, death and reoperation rate were also received. Pulmonary complications were classified as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), prolonged intubation or re-intubation, pneumonia, empyema and bronchopleural fistula. ALI and ARDS were defined by the criteria established at The American-European Consensus Conference: 1) sudden onset of respiratory distress; 2) diffuse pulmonary infiltrates on chest radiograph consistent with alveolar edema; 3) PaO2/FIO2 ratio of < 300 for ALI and < 200 for ARDS; and 4) absence of hydrostatic pulmonary edema on the basis of pulmonary arterial catheterization, echocardiogram, laboratory data and clinical evaluation [4]. Other pulmonary conditions such as atelectasis, effusions and chylothorax were included only if the patient required medical, bronchoscopic, interventional radiology or surgical intervention. Cardiovascular complications included deep venous thrombosis (DVT), pulmonary embolus (PE), any arrhythmias that require acute treatment, and new onset or worsening of heart failure diagnosed on echocardiogram or intravascular monitoring. Renal complication was defined as acute kidney injury (AKI) with absolute increase in serum creatinine of more than or equal to 0.3 mg/dL or more than or equal to 50 % from the base line creatinine, or a reduction in urine output less than 0.5 cc/kg per hour for more than 6 hours. Patient who required blood transfusions for acute decrease in hemoglobin, reoperation for or radiologic finding of demonstrated bleeds were classified as having major hemorrhage.
This study was exempt from Institutional Review Board approval under category 45 CFR 46.101 (b) (4).
The mean hospital and ICU stay were 8.1 and 4.2 days respectively. The chest tube was removed after 5.6 days on average. 45 patients (31.7%) had one or more complications. Pulmonary complications were the most common, occurring in 27 patients (19%) followed by cardiovascular complications in 17 patients (12.0%). Hemorrhage and renal injury occurred in 11 patients (7.7%) and 6 patients (4.2%) respectively. Mortality was 3.5%. The power of this study was 0.90.
Outcomes related to intraoperative IV fluid are shown in Table 2. There was no difference in duration of hospital stay, ICU stay, and chest tube in situ. Patients with one or more complications were observed more frequently in the group receiving liberal intraoperative IV fluid (51.9%, p=0.043). The rate of re-operation was also significantly higher in this group (11.1%, p=0.014). All six patients with acute renal injury occurred in the restrictive group (8.8%, p=0.033). No statistically significant difference was seen in the occurrence of other complications.
Intraoperative fluid < 7cc/kg/hr |
Intraoperative fluid 7-10cc/kg/hr (n=47) |
Intraoperative fluid ≥10cc/kg/hr |
P-value |
|
Age, mean [years] |
67.5 |
67.0 |
63.2 |
0.131 |
Gender, female, n (%) |
27 (39.7) |
29 (61.7) |
17 (63.0) |
0.028* |
BMI, mean |
29.9 |
27.2 |
23.7 |
0.000* |
ASA class > 2, n (%) |
51 (75.0) |
37 (78.7) |
20 (74.1) |
0.868 |
Diabetes, n (%) |
14 (20.6) |
9 (19.1) |
2 (7.4) |
0.297 |
Coronary artery disease, n (%) |
14 (20.6) |
9 (19.1) |
3 (11.1) |
0.551 |
Peripheral vascular disease, n (%) |
5 (7.4) |
3 (6.4) |
2 (7.4) |
0.977 |
Chronic obstructive pulmonary disease , n (%) |
39 (57.4) |
19 (40.4) |
15 (55.6) |
0.181 |
Chronic kidney disease , n (%) |
17 (25.0) |
8 (17.0) |
7 (25.9) |
0.540 |
Chronic alcohol use, n (%) |
5 (7.4) |
6 (12.8) |
2 (7.4) |
0.577 |
FEV1, mean [% predicted value] |
80.4 |
87.3 |
82.4 |
0.141 |
Advanced TMN stages (III-IV), n (%) |
5 (7.4) |
7 (14.9) |
7 (25.9) |
0.053 |
Neoadjuvant chemoradiation therapy, n (%) |
9 (13.2) |
3 (6.4) |
5 (18.5) |
0.273 |
Duration of surgery, mean [min] |
257.7 |
232.6 |
187.2 |
0.001* |
Estimated blood loss, mean [cc] |
169.6 |
136.5 |
140.0 |
0.188 |
Tidal volume per ideal body weight [cc] |
7.9 |
8.2 |
8.7 |
0.046* |
Peak inspiratory pressure [cm H2O] |
25.9 |
25.2 |
24.6 |
0.483 |
Intraoperative fluid < 7cc/kg/hr |
Intraoperative fluid 7-10cc/kg/hr |
Intraoperative fluid ≥10cc/kg/hr |
p-value |
|
Duration of hospital stay, mean [days] |
8.0 |
8.0 |
8.8 |
0.913 |
Duration of ICU stay, mean [days] |
4.4 |
4.2 |
3.9 |
0.950 |
Duration of chest tube in situ, mean [days] |
4.9 |
6.0 |
7.0 |
0.056 |
Patients with one or more complications, n (%) |
18 (26.5) |
13 (27.7) |
14 (51.9) |
0.043* |
Pulmonary complications, n (%) |
12 (17.6) |
7 (14.9) |
8 (29.6) |
0.276 |
Cardiovascular complications, n (%) |
7 (10.3) |
6 (12.8) |
4 (14.8) |
0.812 |
Renal complications, n (%) |
6 (8.8) |
0 (0.0) |
0 (0.0) |
0.033* |
Hemorrhage, n (%) |
4 (5.9) |
2 (4.3) |
5 (18.5) |
0.063 |
Neurologic complications, n (%) |
0 (0) |
1 (2.1) |
1 (3.7) |
0.338 |
Reoperation, n (%) |
1 (1.5) |
0 (0.0) |
3 (11.1) |
0.014* |
Death, n (%) |
3 (4.4) |
0 (0.0) |
2 (7.4) |
0.215 |
Outcomes related to perioperative IV fluid are shown in Table 4. There was no difference in duration of hospital and ICU stay. Duration of chest tube in situ was longer in the high fluids group
Intraoperative fluid < 1.5cc/kg/hr |
Intraoperative fluid ≥1.5cc/kg/hr |
p-value |
|
Age, mean [years] |
66.6 |
66.5 |
0.967 |
Male, n (%) |
22 (55.0) |
47 (46.1) |
0.357 |
Female, n (%) |
18 (45.0) |
55 (53.9) |
|
BMI, mean |
30.4 |
26.9 |
0.001* |
ASA class > 2, n (%) |
33 (82.5) |
75 (73.5) |
0.285 |
Diabetes, n (%) |
10 (25.0) |
15 (14.7) |
0.152 |
Coronary artery disease, n (%) |
10 (25.0) |
16 (15.7) |
0.230 |
Peripheral vascular disease, n (%) |
1 (2.5) |
9 (8.8) |
0.283 |
Chronic obstructive pulmonary disease, n (%) |
19 (47.5) |
54 (52.9) |
0.581 |
Chronic kidney disease, n (%) |
14 (35.0) |
18 (17.6) |
0.043* |
Chronic alcohol use, n (%) |
2 (5.0) |
11 (10.8) |
0.352 |
FEV1, mean [% predicted value] |
80.9 |
83.9 |
0.415 |
Advanced TMN stages (III-IV), n (%) |
1 (2.5) |
18 (17.6) |
0.014* |
Neoadjuvant chemoradiation therapy, n (%) |
2 (5.0) |
15 (14.7) |
0.152 |
Duration of surgery, mean [min] |
243.8 |
232.9 |
0.477 |
Estimated blood loss, mean [cc] |
152.5 |
153.2 |
0.972 |
Tidal volume per ideal body weight [cc] |
8.3 |
8.2 |
0.997 |
Peak inspiratory pressure [cm H2O] |
26.0 |
25.3 |
0.458 |
Perioperative fluid < 1.5cc/kg/hr |
Perioperative fluid ≥1.5cc/kg/hr |
p-value |
|
Duration of hospital stay, mean [days] |
6.2 |
8.9 |
0.069 |
Duration of ICU stay, mean [days] |
3.1 |
4.7 |
0.276 |
Duration of chest tube in situ, mean [days] |
4.3 |
6.2 |
0.010* |
Patients with one or more complications, n (%) |
6 (15.0) |
39 (38.2) |
0.009* |
Pulmonary complications, n (%) |
3 (7.5) |
24 (23.5) |
0.032* |
Cardiovascular complications, n (%) |
2 (5.0) |
15 (14.7) |
0.152 |
Renal complications, n (%) |
2 (5.0) |
4 (3.9) |
0.674 |
Hemorrhage, n (%) |
1 (2.5) |
10 (9.8) |
0.181 |
Neurologic complications, n (%) |
0 (0.0) |
2 (2.0) |
1.000 |
Reoperation, n (%) |
0 (0.0) |
4 (3.9) |
0.577 |
Death, n (%) |
0 (0.0) |
5 (4.9) |
0.322 |
Arslantas et al.[10] reviewed 139 patients who underwent segmentectomy, lobectomy and pneumonectomy and concluded that the intraoperative IV fluid exceeding 6 cc/kg/hr is associated with higher risk of pulmonary complications, with IV fluid more than 8 cc/kg/hr having a particularly high rate of complications. Interestingly, in our study, intraoperative IV fluid less than 7 cc/kg/hr showed no benefit regarding the rate of complications or hospital and ICU stay compare to the group receiving intraoperative IV fluid more than 7 cc/kg/hr and less than 10 cc/kg/hr. In the group receiving more than 10 cc/ kg/hr intraoperatively, we found a higher rate of one or more complication as well as re-operation. Two of three patients in this group who underwent reoperation were due to hemorrhage and one was secondary to bronchopleural fistula and empyema. Although not statistically significant, there was a trend toward higher rates of hemorrhage in this group compare to the other groups receiving lower intraoperative fluids (p=0.063). Young et al.[11] reported reoperation rate of 1%, with the most common cause as hemorrhage in 73% followed by bronchopleural fistula in 11%. The most common source of hemorrhage was the bronchial artery. Our study outcomes were in agreement with this finding. Although direct correlation is unclear, tissue edema secondary to excessive IV fluid may compromised the vascular staple line and interrupted hemostasis. Pulmonary complication was also slightly more common in the group receiving liberal intraoperative IV fluid in our study; however this did not reach statistical significance.
Acute renal injury was more commonly observed in the group receiving intraoperative fluid less than 7 cc/kg/hr. Previous reports have suggested that longer operation times correlate with acute renal injury [12-13]. The duration of operation was statistically longer in patients receiving less IV fluid in our study, and this may be a confounding factor. The patients in our study who developed AKI had a return of their renal function to baseline with medical management without the need for hemodialysis. Furthermore, we observed no additional benefits of restricting intraoperative fluids to less than 7 cc/kg/hr, which suggest that a more typical rate of 7-10 cc/kg/hr may be ideal for intraoperative fluid managements in patient undergoing lobectomy or bilobectomy for NSCLC.
Patients with one or more complications, and pulmonary complications specifically, were more common in the group that received high perioperative IV fluid. Interestingly, duration of the hospital and ICU stay was not affected by the amount of intraoperative or perioperative fluid. Although there are several studies suggesting that the higher amount of perioperative fluids are associated with more pulmonary complications, [6, 14, 15] it is challenging to determine if the complication is due to the IV fluid administration or if increased IV fluids are subsequently given to the patients who had a complication. Our study did not include oral intake in the perioperative fluids, which also limit the ability to accurately measure perioperative fluids.
In our study, male gender, higher BMI and longer operation were associated with smaller amount of intraoperative IV fluid. This suggests that patients were given a similar amount of fluid without consideration of individual weight or length of the surgery. Both surgeons and anesthesiologists must be cautious about this fact to avoid excessive intraoperative IV fluid and potentially elevate the risk of complications.
Our study is limited by its retrospective nature. Since the groups weren’t designated prospectively, it is unclear if there were patient or provider characteristics that influenced fluid management that may have created bias in the data. Furthermore, this study did not look at the use of vasopressors as an adjunct to fluid management. It has been proposed that lowdose vasopressors could potentially help to reduce perioperative fluid requirements and resulting complications, but there is no clear data on the relative outcomes between these strategies [14].
Andres Samayoa had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Caitlin Hodge and Ho Pak contributed substantially to the data collection and the writing of the manuscript.
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