Drainage of symptomatic MA via CVC was safe, provided improvements in some functional QOL scales, diminished all evaluated symptoms, and was positively assessed by patients who had undergone the intervention.
Safety
In a systematic review, generally, 19.7% (255/1297) of patients experienced any complication and 6.2% (81/1297) experienced serious adverse events (SAE) during MA drainage. The rate of complications was different for different drainage methods. After paracentesis for various malignancies, the rate of complications was: 0%–8% (SAE: 0%–5%); drainage using a CVC: 9%–25% (SAE: 0%); permanent peritoneal port: 4%–79% (SAE 0%–4%); tunneled peritoneal catheters: 8%–56% (SAE 0%–39%); for PleurX: 8%–56% (SAE 0%–12%); for Tenckhoff: 9%–29% (SAE 0%); and peritoneovenous shunts: 26%–55% (SAE 5%–33%). The most serious procedure-related complications were reported for peritoneovenous shunts (mortality from pulmonary edema and thromboembolism) [1]. Later published data generally confirmed a relatively safe profile of MA drainage with paracentesis and drains [9-12]. However, some details need attention.
One-time insertion of a permanent catheter (also vascular catheter) into the abdominal cavity should be performed under ultrasound control to minimize the risk of potential injuries (bowel, vascular, other) related to the procedure of insertion. If done without imaging control can end with fatal bowel perforation (1% of a cohort undergoing drainage) [11].
Peritonitis is one of the most significant and serious adverse events of prolonged ascites drainage via permanent catheters [1]. Also, in more recent publications peritonitis is still an important issue, that is reported with different frequencies: 1% with paracentesis / indwelling catheter (pigtail) [11]; 2% with the usage of the peritoneal catheter [10], however information on the outcome of the complication is lacking in both cited studies. There were 4.4% peritonitis (6/137) complications after drainage of ascites via a tunneled peritoneal catheter (PleurX, 19-gauge), and one catheter-associated death (bacterial peritonitis; 0.8%) [12]. In another study, where tunneled indwelling peritoneal catheters were placed for the management of recurrent MA in 48 patients, the rate of bacterial peritonitis was as high as 8.8%, with all patients responding to antibiotics and only one required catheter removal [13]. Chen et al reported retrospectively on outcomes of 26 patients with inserted tunneled intraperitoneal ports (subcutaneous). Interestingly, the mean number of times each port was accessed was 10 (range: 1–90), which was possible at patients’ homes too, so prevented repeated paracentesis. However, reported rates of cellulitis and peritonitis were 7% and 12% per patient and per port, respectively. Unfortunately, the authors did not provide management and outcomes of peritonitis [9]. It seems that either there must be some additional risk factors that peritonitis may become lethal (e.g. performance status, end-stage malignancy), or there are different definitions of peritonitis. An example of a very broad peritonitis definition was used by Chen et al: peritonitis was defined by abdominal pain or fever with ascites and an absolute neutrophil count greater than 250 cells per microlitre and/or positive ascites fluid or blood culture [9]. Of note is one study because its results differ from others [14]. In a retrospective, observational study, bacterial colonization of the catheter without immediate infection was noted after a mean time of 18 days in 69 of 143 patients following catheter insertion (43,5%). After a median of 14.5 days, thirty patients developed drain-related infection, accounting for 43.5% of those with prior positive bacterial colonization of the drain and 21% of all patients. Among those (n=69), 5 (7,2%) developed drain-related peritonitis, and 4 died from the infection (80% of deaths after the diagnosis of peritonitis, and 13.3% of deaths among all patients who developed drain-related infection). Other forms of infection were defined as drain-site cellulitis (20%), infected ascitic fluid without clinical features of peritonitis (26.7%), fever or sepsis without other demonstrable foci (10%), and physician-diagnosed drain-related infection (36.7%) [14]. One must note that the frequency of infection complications was higher in the Chan et al. group as compared to previously reported (0 – 1.9% for G2 infections, and 0 – 5.7% for G3 infections) [1]. Notably, one-third of the patients had hepatocellular carcinoma (HCC), and 27.5% of the patients had comorbid liver cirrhosis, and the multivariate analysis revealed that HCC [odds ratio (OR): 8.85; 95% confidence interval (CI): 1.86–42.07, P=0.006] and decrease in body weight (OR: 1.20; 95% CI: 1.02–1.42, P=0.03) were the only risk factors for developing infection complications [14]. The probable explanation for the higher risk and incidence of ascitic fluid infection among patients with liver failure was described elsewhere [15]. The risk of peritonitis during ascites drainage was higher in patients with end-stage liver disease (8.3%) [16] than in those with other malignancies (2.5%) [17]. Based on the research discussed herein, we should acknowledge a difference in the risk of infection during ascites drainage, between patients with ascites secondary to massive liver involvement (e.g., HCC, liver metastases) versus peritoneal carcinomatosis. These patients should probably be independently analyzed in future research studies [18], however, it is debatable [19].
The larger the diameter of a catheter, the more risk of complications, including infections [20]. Dedicated peritoneal catheters (e.g. PleurX) have larger diameters (5.2 mm) [10], than vascular catheters (2.2 mm) inserted into the abdominal cavity [21]. Also, the longer catheter dwell time the higher the risk of infectious complications [12].
Hyponatremia is another possible complication of prolonged MA drainage, however it may not have clinical significance, because it is often untreated or unrecognized. Nevertheless, a risk group of patients with hepatopancreatobiliary malignancy and hyponatremia before drainage was suggested for routine testing of plasma sodium concentration, because hyponatremia may have significant negative implications [22]. In another study sodium values declined both pre- and post-procedure (tunneled catheter insertion followed by drainage); the slope of decline diminished postprocedure compared with pre-procedure (sodium slope [–2.50 to 1.31 mEq/L, p = 0.037]). No clinical relevance of the laboratory results was provided [23].
Loculation of ascites is another complication that can happen in 2% of patients [13] after prolonged drainage, or repeated paracentesis. It needs to be addressed because no single drain can solve the problem.
It seems that the variability in mean arterial pressure during drainage of MA is not dependent on drainage volume (two groups were compared: drainage of large (5-10 L) vs small (<5 L) volume) [24]. However, the “drainage to dryness” should not be the aim. It was shown that even small-volume (1.5-2.5 L) paracentesis could alleviate abdominal distension of terminally ill cancer patients with MA without shortening the paracentesis interval compared with moderate-volume (>2.5 L) paracentesis. Only drainage of a minimal volume (<1.5 L) was the risk factor (HR: 2.34) for a shorter interval to the next paracentesis [25]. In the case of permanently placed drains/catheters, the repeating paracentesis is not the case. Thus, the ascites drainage volume should rather be adapted to individual patients, with the main aim of controlling symptoms and improving QOL. Additionally, in one study it was shown that the median mass of MA was 3 240 – 3 480 g, with a maximum as high as 14 350 g [26], thus evacuation of ascites may increase a patient’s mobility.
QOL
QOL measured with EORTC QLQ-C30 before paracentesis for MA revealed that global QOL and emotional functioning were worse in patients with MA [26] as compared to a reference of all cancer patients [27] (38.9-41.1 vs 61.3 and 56.3-61.6 vs 71.4, respectively). Also, symptoms were more severe among patients with MA [26] than the reference [27] (24.7-63.4 vs 9.1-34.6) [26].
QOL before and after drainage can be measured with simple scales. In a small retrospective study (n=30), on a 10-point scale, QOL compared to that before subcutaneous peritoneal and pleural port catheter placement, improvement was rated a mean of 9.5 by patients and 9.0 by the nursing staff. Both patients and nurses reported a high degree of convenience (rated at 9.7 and 9.6, respectively) and improvement of symptoms and comfort (9.6 and 9.3, respectively) [28].
In a prospective, longitudinal study of patients with refractory ascites associated with stage IV or end-stage malignancy who underwent percutaneous tunneled catheters (Tenckhoff) insertion in interventional radiology at a single institution, QOL was tested with EORTC QLQ-C30 and McGill QOL questionnaires, prior the procedure (n=47) and at 1 (n=37) and 3 (n=20) weeks during the drainage. A significant improvement was demonstrated in global QOL, functional role, emotional, and cognitive scales at 1 week. Also, significant symptom improvement was seen in fatigue, nausea/vomiting, pain, dyspnea, insomnia, and appetite loss. This improvement was sustained at 3 weeks for dyspnea, insomnia, and appetite [23].
In a longitudinal study that captured patient responses on selected symptoms and QOL instruments immediately before and 24 h after paracentesis for symptomatic ascites, it was shown that the evacuation of the fluid significantly improved mobility, appetite, decreased shortness of breath, fatigue, and level of anxiety and depression. It also improved role functioning, however had no impact on global QOL nor the social and physical functioning, and caused worse cognitive functioning [4].
Easson et al. evaluated the measurement properties of selected existing validated symptom and QOL questionnaires in patients undergoing paracentesis for symptomatic ascites. They tested 4 different questionnaires and suggested that the EORTC QLQ-C30 and the ESAS:AM (Edmonton Symptom Assessment System–Ascites Modification) together, or the QLQ-C30 with the addition of the QLQ-PAN26 (EORTC 26-item pancreatic cancer module) ascites and abdominal pain subscales could be used [29]. However, these questionnaires are complex and may not be suitable for many patients suffering symptoms of ascites and advanced malignancy. According to our observations, most patients are reluctant to concentrate on reading, understanding, and completing complex questionnaires. Their primary goal is to handle symptoms and they often face anxiety and depression. Thus, if completed under pressure, the results of complex questionnaires may be significantly biased. That is why we decided to use the shortest and easiest possible validated tools to assess QOL changes.
Others measured changes in QOL by a systematic telephone review focusing on ascites-associated symptoms (using a five-point scale). The abdominal discomfort, impaired mobility, dyspnea, fatigue, nausea, and vomiting were significantly reduced 30 days after PleurX (tunneled, permanent drain) insertion (p<0.05) [10].
Other considerations
In a palliative setting, median survival after drain insertion was 19 days (one-third survived less than 2 weeks). Thus, Murray et al suggested that in cases with symptomatic ascites, insertion of drains and drainage should not be delayed [3]. Contrary, in the study by Wimberger et al. QOL of patients undergoing repeated paracentesis for MA were tested for up to 7 months (no data on overall survival). Importantly, half of the patients had ovarian cancer in this trial [26]. In another cohort, median survival was 38 days after placement of tunneled drainage catheters (ovarian cancer constituted 18.8%) [23]. Thus, the timing of catheter insertion for permanent ascites drainage should be individually considered and not delayed for symptomatic patients. It is even more important if larger procedures, like tunneled catheter implantation, are planned. As suggested by Korpi et al., patients with ascites secondary to advanced pancreatic cancer may as well benefit from repeated paracentesis, instead of being subjected to more invasive procedures like insertion of larger catheters [30]. Of note is that smaller catheters, like the CVC, can be easily inserted, even in an ambulatory setting as shown in our study and the previous ones [21, 31, 32].
Another issue is the economy. According to research by Wu et al. tunneled peritoneal catheter was the most cost-effective strategy when compared to repeated large-volume paracentesis in patients with recurrent ascites from gynecological malignancy [33]. Even more significant economic benefit may be expected if CVC was used because the procedure of insertion is much easier than it is for tunneled catheters.
The limitations of our study include the population of patients with MA, among which ovarian cancer patients were the most frequent, results are based on prerequisite data collection tools, and the main settings of recruiting institutions were cancer centers (not palliative departments) and thus our results may not be generalized to all clinical settings.