Metropolitan W135 meningococcal compressive pericarditis treated with intrapericardial fibrinolysis

Abstract

Meningococcal pericarditis is a rare but severe form of acute purulent pericarditis. It is a classic complication of Neisseria meningitidis of serotype W135, usually occurring in pilgrims to Mecca and their household contacts. This severe form of meningococcaemia is difficult to diagnose and evolves frequently and gradually towards a tamponade, requiring emergency drainage. We report a case of meningococcal pericarditis caused by N. meningitidis W135 in an immunocompetent patient, without any other organ involvement especially meningeal, requiring pericardium drainage in emergency and then intrapericardial fibrinolysis.

Background

Meningococcal meningitis occurs sporadically around the world in small groups of cases (annual incidence rate: 1–5 cases/100 000 inhabitants, 500 000 cases per year according to WHO). Meningococcal disease affects mostly an area of ​​sub-Saharan Africa known as the ‘meningitis belt’.

In 2011, the sex ratio M/F of invasive meningococcal disease was 1.2.¹ The median age was 16 years with a higher proportion of invasive infection with Meningococcal W135 between 25 and 59 years old (7%).¹ The lethality of these severe infections in France was 10% in 2011 (7% in the W135 serotype¹). In 2014, the French Health Monitoring Institute (InVS) survey reported 426 cases of invasive meningococcal infections in France, including 4.5% with serogroup W.¹

Since 2015, an upsurge in serogroup W meningococcal invasive infections has been observed in France,² concomitantly with the clonal expansion of the South American/UK strain.³ This strain was first detected in South America,⁴ and then spread to the UK⁵ and more recently to Spain,⁶ Australia⁷ and the Netherlands.⁸ In our particular area (28-Eure et Loir-France), the incidence rate (per 100 000 inhabitants) of meningococcal invasive infections has decreased since 2011.⁹

We present a case of meningococcaemia complicated by a constrictive purulent pericarditis. Delay in diagnosis, due to the absence of specific symptoms, caused significant therapeutic difficulties.

Case presentation

A late 60s male patient presented to the emergency room with alteration of the general state for 4 days associated with fever at 39°C. His medical history included cardiac arrhythmia without cardiac dysfunction. He lived in a residential home, had never travelled abroad and was under guardianship for mental retardation.

On physical examination, the Glasgow score was 15, he was afebrile at 36°C, blood pressure was 79/57 mm Hg with following respiratory distress signs: tachypnoea at 28 cycles per minute and hypoxia at 88% without oxygen. Capillary blood glucose was normal (4.4 mmol/L). There were no headache or neck stiffness, no haemorrhagic skin lesions. Initial laboratory tests showed leucocytes at 17.5 G/L (neutrophils=91%), serum creatinine at 6.9 mg/dL, blood urea nitrogen at 3.5 mg/dL, total plasma CO₂ at 12 mmol/L, C reactive protein at 48.5 mg/dL and procalcitonin over 200 ng/mL without other electrolytic alteration. Liver function and haemostasis were conserved. The ECG indicated atrial fibrillation at 150/mn, without the characteristic electric sign of pericarditis such as ST-elevation or microvoltage (figure 1). A chest X-ray was performed in a bedridden patient, revealing a possible early right lower lobe pneumonia, with no obvious evidence for pericardial effusion (figure 2). The diagnosis of a community-acquired pneumonia was suspected and an empirical antibiotic therapy (cefotaxime and spiramycin) with high flow oxygen therapy was introduced.

Figure 1.

Admission ECG.

Figure 2.

Admission thorax X-ray.

During the first 2 days, evolution was marked by an acute kidney injury with acidosis requiring intravascular volume expansion and haemodialysis. The clinical condition of the patient progressively deteriorated towards a septic shock with haemodynamic, respiratory and renal failures. Invasive mechanical ventilation, haemodynamic support (norepinephrine 10 mg/h) and citrate continuous venovenous haemodialysis were then performed.

Investigations

The transthoracic and transoesophageal cardiac echography, performed 2 days after admission, revealed a circumferential pericardial effusion >2.5 cm, with pretamponade sign (figure 3).

Figure 3.

Transthoracic ultrasound, under epicardium window.

Treatment

More than 500cc of a purulent fluid was collected on emergency drainage by Fuhrman drain. Neisseria meningitidis W135 of intermediate sensitivity to penicillin was isolated from blood cultures and pericardial fluid. Antibiotic treatment with cefotaxime was continued for a total duration of 14 days.

Surgical drainage was performed 2 days later after the failure of skin drainage and intrapericardial fibrinolysis (urokinase 100 000 UI 2 days in a row). The procedure consisted of an incision under the xiphoid to access the pericardial cavity. The first incision disclosed a purulent postpericarditis compartmentalisation. A 28-French strainer drain allowed the evacuation of 300cc of purulent liquid.

Less than 12 hours following the surgical drainage, a new brutal haemodynamic degradation occurred (norepinephrine 3.5 mg/h) with anaemia (7 vs 10.5 g/dL) and moderate haemoperitoneum. Haemodynamic failure and bleeding were controlled by transfusion of three red blood cells (haemoglobin at 11 g/dL after transfusion). A new transoesophageal cardiac echography showed, a few hours later, a bulky and compressive intrapericardial thrombus, left retroauricular (figure 4). A second intrapericardial fibrinolysis was performed, following the same protocol.

Figure 4.

Transoesophageal ultrasound, intrapericardial thrombus.

Simultaneously, the patient experienced clinical worsening because of a septic shock due to ventilator-associated Pseudomonas aeruginosa pneumonia. The haemodynamic status improved progressively, with both antibiotics and drainage (1000cc in 72 hours) by the spontaneous lysis of the thrombus 7 days after.

Outcome and follow-up

The evolution of pericarditis and intrapericardial thrombus were favourable.

Nursing continued for several weeks because of intensive care-acquired infections, including one Enterobacter cloacae complex BLSE bacteraemia secondary to a dialysis catheter infection, and four successive ventilator-associated P. aeruginosa pneumonia, each time with a different antibiotic resistance profile.

The patient finally died, 8 weeks after admission due to a multiorgan failure including haemodynamic, renal and severe ARDS.

Discussion

The first disseminated meningococcal infection with pericarditis was reported in 1918, but it was in 1939 that a primary meningococcal pericarditis without meningeal involvement or clinical meningococcaemia was described for the first time.¹⁰ Finkelstein et al suggested in 1997 a new classification of the various states of meningococcal pericarditis on the basis of the pathophysiological process: disseminated meningococcal disease with pericarditis (purulent, culture-positive, associated with meningococcal bacteraemia); isolated meningococcal pericarditis (purulent, culture-positive but without signs of meningeal or other clinical systemic involvement); and reactive meningococcal pericarditis (immunological, late-onset, culture-negative, resembling post-viral pericarditis).¹¹ From 1999 to 2002, in France, invasive meningococcal disease was bacteriologically confirmed in 1956 cases/2152, including 6 cases of pericarditis.^{1 12}

We describe a case of France acquired invasive meningococcal disease with pericarditis complicated by cardiac tamponade without initial right ventricular failure and without evidence of meningococcaemia.

Untreated purulent pericarditis always leads to death, and even with proper multidirectional treatment, mortality rate reaches 40%.^{13 14} No specific guidelines and management recommendations have been issued by medical societies, neither by European Society of Cardiology guidelines¹⁴ nor the American Heart Association and American College of Cardiology, until 2015.¹⁵ In the current state of knowledge, in case of constricting bacterial pericarditis, percutaneous pericardiocentesis must be performed. Drainage and rinsing of the pericardial cavity, combined with effective systemic antibiotic therapy is mandatory.^{14 15} The feasibility of pericardiocentesis is high (>95% of cases) with echocardiography guidance, mostly in patients with anterior effusion. The most serious complications of pericardiocentesis are laceration and perforation of the myocardium. The safety was improved with echocardiography guidance.¹³

Intrapericardial fibrinolysis, by frequent irrigation of pericardial cavity with urokinase or streptokinase, has been proposed without clear recommendation as a way to prevent cardiac tamponade and constrictive pericarditis evolutions in patients with purulent pericarditis. In fact, the objective of fibrinolysis is to target fibrin formation, in order to decrease fluid thickness to optimise its evacuation and therefore to prevent both persistent purulent pericarditis and constrictive pericarditis.^{16 17} Nevertheless, the European Society of Cardiology Guidelines finally defined in 2015 intrapericardial thrombolysis as a possible treatment for cases with loculated effusions in order to achieve adequate drainage before resorting to surgery (IIa,C),¹⁵ but no therapeutic protocol have been clearly proposed.

The first complication of intrapericardial fibrinolysis is an allergy, which occurs mostly in cases of repeated instillation of streptokinase. The use of urokinase can reduce this risk.¹⁸ The second risk is major haemorrhage, but this could be a consequence of the purulent pericarditis and not directly related to fibrinolysis. Indeed, systemic effects are usually not detected on coagulation laboratory tests.¹⁹ The third risk is tamponade, which may occur if the instilled volume is not evacuated by the drain.

In the case reported here, one might question the indication of the first intrapericardial fibrinolysisand whether the thrombus appearance was avoidable.

Percutaneous drainage of pericardial effusion was complicated by multiple obstructions of Fuhrman drain. Intrapericardial fibrinolysis by 100 000 UI of urokinase, 2 days in a row, in order to liquefy exudate, appeared as the best option considering current evidence.

A compressive thrombus developed the day after the surgical laying of a pericardial drain (28Fr) with minimal postoperative bleeding. This could probably have been avoided by the use of a larger drain (>32 Fr), thus facilitating the evacuation of the haemopericardium. Also, prior optimisation of haemostasis (preoperative prothrombin time : 49%, activated partial thromboplastin time (TC: 1.5, no thrombocytopaenia) with perfusion of 2 frozen plasma before surgery might also have been insufficient, although surgical haemostasis was described as complete. In that case, emergency pericardiotomy has not been considered by cardiac surgery specialised advice because of the initial haemodynamic instability with multivisceral failure due to septic shock.

Clearest recommendations may arise from results of a meta-analysis currently conducted in South Africa, where HIV has been responsible for an increased incidence of pericarditis. This study might help to determine whether complete pericardial drainage with intrapericardial fibrinolysis reduces the incidence of cardiac tamponade, persistent or recurrent pericardial effusion and how it can be safely performed with respect to the risk of haemorrhage.²⁰

Learning points.

• Diagnosis of purulent pericarditis should be considered in case of septis with unknown aetiology, even with a frustrating clinical presentation.

• Drainage in absolute emergency is mandatory in case of constrictive pericarditis (purulent or not).

• Intrapericardial fibrinolysis should be discussed as second-line therapy as a less invasive alternative to surgery.