Discussion

Pericardial effusion is asymptomatic in most patients, and regresses spontaneously; however, moderate and severe pericardial effusion can progress to cardiac tamponade, which causes life-threatening haemodynamic deterioration and may require urgent pericardiocentesis or surgical drainage. More urgent intervention is required in children due to the lower tolerance to ventricular stroke volume reduction compared to adults.

In a multicentre study by Bolin et al. including 9902 patients with pericardial effusion, pericardiocentesis was performed in 15% of the patients. ^{Reference Bolin, Tang and Lang8} Mehdizadegan et al. reported that pericardial effusion was present in 0.23 % of all hospital paediatric admissions. Of these patients, 32.6% had moderate to large pericardial effusion having tamponade signs in 2% and pericardiocentesis were performed in 14.1%. ^{Reference Mehdizadegan, Mohammadi and Amoozgar7} In our study, signs of tamponade were present in 23.7% of our patients.

Male-to-female ratio was found 2.16, which varied according to age group with a prominent male predominance (male to female:7.5) over 3 years of age. Shakti et al. reported a male-to-female ratio of 2.45 in patients who developed pericardial effusion due to idiopathic and viral pericarditis, while it was around one in the preadolescent age and approximately five in the adolescent age group. ^{Reference Shakti, Hehn and Gauvreau4} In our study, in accordance with Shakti et al. it was 7.5 in patients over 3 years of age. In light of these findings, it was determined that the probability of its occurrence in the male gender increased with increasing age in the paediatric age group. Although the cause is not clear, it is thought that sex hormones may have an effect on viral concentration, immune response, and susceptibility to disease, as in adolescent men with myocarditis.

In our study, the mean age of the patients was 14 months and 21% of the patients were in the neonatal age group with a body weight varying between 0.8 and 80 kg. In the literature, the median age of the patients with pericardial effusion was reported as 10–11 years. ^{Reference Bolin, Tang and Lang8,Reference Abdel-Haq, Moussa and Farhat9} Especially the presence of premature patients and the absence of any significant complications related to the technique showed that percutaneous pericardiocentesis can be performed safely in all age groups by providing a suitable environment.

Considering the complaints at the time of admission in our study, at least one complaint was reported in 89.7% of the patients. The most common complaints were respiratory distress (51.7%) and chest pain (37.9%). In the literature dyspnoea, chest pain and fever were reported as leading symptoms. ^{Reference Mehdizadegan, Mohammadi and Amoozgar7,Reference Ozturk, Cansaran and Saygi10} It should be kept in mind that atypical findings such as fatigue and abdominal pain may be associated with pericardial effusion and tamponade.

The classical triad of tamponade is hypotension, jugular venous engorgement, and decreased heart sounds; however, very few patients have all three of these findings. ^{Reference Stolz, Valenzuela and Situ-LaCasse11} In the study by Akthar et al. including 36 patients with moderate to severe pericardial effusion, it was reported that tamponade findings were present in 39%. ^{Reference Akhtar and Malik12} Pulsus paradoxus increases the risk of tamponade 3.3 times in the presence of pericardial effusion; ^{Reference Roy, Minor and Brookhart13} however, its evaluation may not be reliable, especially in a young and agitated child. Hearing deep heart sounds and jugular venous engorgement has 28% and 76% sensitivity, respectively. ^{Reference Roy, Minor and Brookhart13–Reference Spodick15} One of the earliest signs of tamponade, tachycardia, was detected in 47% of our patients; it has been reported to have a sensitivity of 77%. ^{Reference Roy, Minor and Brookhart13} Non-specific findings or unexplained haemodynamic disturbance may be observed in newborn patients. ^{Reference Nowlen, Rosenthal and Johnson16} Considering that 21% of the patients were in the neonatal period, evaluation with echocardiography is recommended, especially in the presence of unexplained findings in this period.

The earliest echocardiographic sign of haemodynamic deterioration in cardiac tamponade is collapse of the right atrium in early systole and the right ventricle in early diastole (Figure 1). Collapse in any cardiac cavity has 90% sensitivity and 65% specificity for tamponade. ^{Reference Mercé, Sagristà-Sauleda and PermanyerMiralda17} In our study, due to the different age groups of patients, these measurements were also evaluated by proportioning to body weight. Haponiuk et al. defined the “Pediatric tamponade index (PTI)” by proportioning the amount of fluid drained for 24 hours with the inserted chest tube to body weight. They suggested that the initial clinics of patients with paediatric tamponade index > 21 were more severe and may be associated with a longer hospital stay and higher inotropic requirement after pericardiocentesis. ^{Reference Haponiuk, Kwasniak and Chojnicki18}

The appearance of pericardial fluid was haemorrhagic in 51.4% of patients. Haemorrhagic effusion has been related to trauma, malignancy, vascular tumour, tuberculosis, bleeding diathesis, vasculitis, uraemia, aortic dissection, and iatrogenic causes. ^{Reference Spodick19} Although rare, it may also develop after chlamydial infection as in our case . ^{Reference Tenenbaum, Heusch and Henrich20}

In children, large pericardial effusion can develop as a finding of many local or systemic diseases. While tuberculosis is still the most common aetiology in developing and underdeveloped countries, viral and idiopathic pericarditis are more common in developed countries. ^{Reference Peter, Asani and Aliyu6,Reference Bagri, Yadav and Agarwal21,Reference Khanal, Gajurel and Sahi22} When our patients were examined according to aetiology, 44% were classified as inflammatory (idiopathic and infectious), 11% rheumatological disease, 11% iatrogenic causes, 8% malignancy, 8% cardiomyopathy, and 18% other. In retrospective study by Bolin et al. ^{Reference Bolin, Tang and Lang8} and K FC;hn et al., ^{Reference Kuhn, Peters and Marx3} idiopathic and neoplastic causes were leading aetiologies. ^{Reference Bolin, Tang and Lang8} The reason for this difference is thought to be that our study only included large effusions and pericardiocentesis data.

In the study by Bolin et al., it had been suggested that undetermined viral infections may be responsible for idiopathic pericardial effusion due to the fact that mortality and re-admission rates were found to be similar in idiopathic and viral aetiologies. ^{Reference Bolin, Tang and Lang8} When classified together, the viral and idiopathic groups constituted 26% of our patients. Patients with purulent effusions thought to be bacterial but no bacterial growth in blood or pericardial fluid cultures were observed to have had a history of antibiotic use before admission, and therefore the causative agent was not detected. In these patients, bacterial infection was diagnosed based on the appearance of the effusion and supporting clinical and laboratory tests. Mok et al. reported that 38% of patients with severe pericardial effusion had bacterial infection, and in 48% of these, no causative agent could be detected. ^{Reference Mok and Menahem2} In an adolescent patient with pericardial effusion due to chlamydial infection, a simultaneous pleural effusion was observed, and improvement was achieved with antibiotic treatment. Two siblings in our study, whose aetiology could not be determined despite detailed history and examinations and one of whom had recurrent effusion, were accepted as having recurrent idiopathic pericarditis and were followed up with colchicine treatment.

Tuberculosis remains as one of the main causes of haemorrhagic pericardial effusion, especially in developing countries, accounting for approximately 1–2% of cases of acute pericarditis, with tamponade reported in 7% and mortality rate varying between 14 and 40%. ^{Reference Peter, Asani and Aliyu6,Reference Khanal, Gajurel and Sahi22} G FC;ven et al. ^{Reference Guven, Bakiler and Ulger23} from our country and Akhtar et al. ^{Reference Akhtar and Malik12} reported that tuberculosis was shown as the causative agent in 30% and 11.1% of the patients with pericardial effusion, respectively. Diagnosis is made by direct detection of M. tuberculosis in tissue or fluid culture, histopathological observation of bacilli or granulomas, observation of granulomas in the pericardium in patients with a history of extracardiac tuberculosis, and response to tuberculosis treatment. Tuberculosis growth in pericardial fluid occurs in 1/3 of the cases. ^{Reference Cherian24} In addition, studies have reported that elevated adenosine deaminase in pericardial fluid with a value of 63–117 U/L is 100% sensitive and 83.3% specific in the diagnosis. ^{Reference Mathur, Tiwari and Trikha25} In our study, the M. tuberculosis was shown by both culture and PCR results in one patient and pericardial fluid adenosine deaminase level was found as 81.1 U/L. This patient died during follow-up due to disseminated involvement and sepsis.

Neoplastic diseases were detected in 8% of the patients diagnosed with carcinoid type neuroendocrine tumour, T-cell lymphoblastic lymphoma, and B-cell acute lymphoblastic lymphoma. Although the malignancy rate was found to be 24% in the multicentre study by Bolin et al., ^{Reference Bolin, Tang and Lang8} in studies including only patients who underwent pericardiocentesis, it was reported as 7–20% . ^{Reference Ozturk, Cansaran and Saygi10,Reference Akhtar and Malik12} Medary et al. reported that the most common diagnoses in patients with malignancy who developed pericardial tamponade during follow-up and underwent pericardiocentesis were acute leukaemia and lymphoma. ^{Reference Medary, Steinherz and Aronson26}

Mild fibrinous pericarditis or mild effusion is usually present in vasculitis or connective tissue diseases, but rarely massive effusion may be seen. Rheumatological diseases were detected in four (11%) patients, systemic lupus erythematosus and familial mediterranean fever (FMF) in two patients each. FMF, which is relatively common in our country, was detected at a rate of 15%. ^{Reference Ozturk, Cansaran and Saygi10}

The prognosis of pericardial tamponade in newborn patients is poor and is usually associated with heart failure, fetal restrictive cardiomyopathy, concomitant malformations, chromosomal abnormalities, fetal infections, intrauterine growth retardation, non-immune hydrops fetalis, erythroblastosis fetalis, and central and peripheral venous catheters. ^{Reference Haponiuk, Kwasniak and Chojnicki18} In our study, 11 patients under 3 months of age, seven of whom were premature, underwent pericardiocentesis in three due to central catheter-related complications, two due to non-immune hydrops, two due to perforated NEC and sepsis, one due to respiratory distress syndrome and sepsis, one due to congenital myopathy-related heart failure, one due to hypertrophic cardiomyopathy, and one due to pneumopericardium and effusion after cardiopulmonary resuscitation. Pericardial effusion and tamponade constitute 0.7% of central catheter-related complications. It develops on average 3 days after the procedure and can develop on the same day as the procedure or even 112 days after the procedure . ^{Reference Nowlen, Rosenthal and Johnson27} Although the aetiology of pericardial effusion in these patients is not clear, it has been suggested that damage to the endothelium may occur as a result of repeated traumas at the catheter tip, thrombus formation at the catheter tip as a result of adhesion and activation of platelets, and osmotic damage due to infusion may occur as a result of the tip of the catheter touching the heart and has also been reported in patients with a normal umbilical venous catheter position. ^{Reference Onal, Saygili and Koc28,Reference Bentata, Hamdi and Chemlal29} Pericardiocentesis plays a role in these patients both as an emergency and definitive treatment. In the study by Novlen et al., mortality was reported as 8% in patients who underwent pericardiocentesis and 75% in those who did not. ^{Reference Nowlen, Rosenthal and Johnson27}

A patient who presented with tamponade and was found to have chylohemorrhagic pericardial effusion, multiple lytic lesions, and compression fractures in the vertebrae was diagnosed with Gorham-Stout syndrome with lymphatic drainage problems.

Pericardiocentesis was performed in one patient for pericardial effusion due to chronic renal failure. The aetiology of uraemic pericarditis is multifactorial. Albuminuria seen in these patients is associated with inflammatory abnormalities and pericarditis develops in the low inflammatory process as a result of increased endothelial permeability due to albuminuria. ^{Reference Abdel-Haq, Moussa and Farhat9,Reference Bentata, Hamdi and Chemlal29}

Treatment varied depending on the underlying disease. Although NSAIDs are primarily preferred in treatment, colchicine has recently become widely used in acute and recurrent pericarditis. Double-blind and placebo-controlled adult studies have shown that colchicine use reduces recurrences, duration of symptoms, and hospitalisation rates. ^{Reference Imazio, Brucato and Cemin30} In our centre, colchicine use has increased in parallel with the trend in the literature. No significant complications were observed in our clinic due to colchicine use. It was observed that two patients (11.1%) with continuing pericardial effusion despite medical treatment underwent surgical pericardial tube insertion and pericardial window operation.

Of the 38 patients who underwent pericardiocentesis, eight (21%) died during follow-up. In the study by Bolin et al., mortality was reported as 8.2% in all pericardial effusion cases . ^{Reference Bolin, Tang and Lang8} Six of our patients who died were under 3 months of age; two were diagnosed with hydrops fetalis, two with perforated NEC and sepsis, one with dilated cardiomyopathy, and one with hypertrophic cardiomyopathy. Although the mortality rate was high in our study, it was thought that this was due to the age group distribution of the patients and the inclusion of only patients with large pericardial effusion.

Although the most common approach for pericardial fluid drainage is subxiphoid percutaneous intervention, minimally invasive surgical intervention is also used in some centres. ^{Reference Haponiuk, Kwasniak and Chojnicki18} In our centre, pericardiocentesis and/or pericardial catheter placement with a subxiphoid percutaneous approach is preferred. Although the number of newborns and low body weight patients who were more prone to complications in our study was high, we think that the percutaneous approach is more appropriate because no serious complication related to the procedure was observed and the success of the procedure was high. In case of surgical intervention, it seems to be a disadvantage to intervene in patients under operating room conditions and accompanied by general anaesthesia. We think that surgical intervention is more appropriate in patients who require a pericardial window due to the locality of the collection, the presence of widespread fibrous structures and the recurrent nature of the collection.