Aseptic peritonitis: role of icodextrin

R. Montagnac1, A. Slingeneyer2 and F. Schillinger1

1 Department of Nephrology, Troyes Hospital 2 AIDER, Montpellier, France

Sir,

Case.

A 56-year-old patient with mesangial IgA nephropathy started continuous ambulatory peritoneal dialysis (CAPD) treatment in May 1995. In February 1996, sigmoidectomy (with concomitant cholecystectomy for multiple gall-stones) was performed for severe diverticular sigmoiditis. Subsequent failure of restart of peritoneal dialysis (PD) was due to poor drainage. Celioscopy showed that the catheter was obstructed in numerous partitions in Douglas' cul-de-sac and allowed for adhesiotomy of multiple adhesions. In May 1996, the patient started an anti-tuberculosis treatment because he had a history of tuberculosis lymphadenitis in childhood and was a candidate for kidney transplantation. In March 1997, an abdominal X-ray showed that the tip of the catheter was located in a sub-splenic position.

To complete clearance and ultrafiltration, this corpulent subject (91 kg, 181 cm), was transferred to automated peritoneal dialysis (APD) in July 1997 with the following programme: 15.0 l 1.36% glucose per night, over 10 h (volume of 1.5 l per cycle) and occasional use during the day of a 2-l bag of 3.86% dialysis fluid, soon replaced by one 2-l bag of Icodextrin daily, administered over 13 h, enabling sufficient ultrafiltration. In January 1998, he was treated for an infection at the catheter exit site due to Staphylococcus non-aureus with subsequent granulation tissue formation.

In April 1998, the patient was hospitalized for suspected peritonitis with abdominal pain for 3 weeks, predominately in the left flank. A cloudy and fibrinous effluent fluid contained 410 leukocytes/mm3, 78% neutrophils. However, cultures remained negative and antibiotherapy did not correct the symptoms or the high dialysate cell count during this first episode or during subsequent recurrences.

In May, Icodextrin was withdrawn and the drainage fluid became clear without improvement in cell counts. Home APD without Icodextrin resumed (except on 5 and 19 June when the patient used a bag yielding 600 ml of ultrafiltrate), without cloudiness of the drainage fluid. The patient often remained non-febrile (37.8° to 38.1°C).

The hypothesis of a peritoneal reaction to Icodextrin or one of the batches used, either allergic or toxic, was proposed, and use of Icodextrin solution was finally discontinued. The patient reported that abdominal pain was no longer present at night but persisted in the left flank, on changing position, beginning in the morning and intensifying throughout the day until evening, but was less severe than it had been. A cell count of the drainage fluid showed only 110 leukocytes/mm3, with 97% lymphocytes in contrast with previous cell distribution.

By the end of August 1998, when all had returned to normal, a loss of ultrafiltration, not corrected by recourse to hypertonic fluids, led to transfer to haemodialysis. The catheter rapidly became obstructed and could no longer be used. Sub-umbilical median laparotomy was conducted to remove the catheter on October 29th. The findings included (i) very numerous ileoparietal and ileoileal adhesions that made it impossible to penetrate the peritoneal cavity; (ii) the dome of the bladder had an abscess containing 5 cc of thick pus; (iii) traction on the catheter showed that it was free from its intra-tunnel segment up to the intraperitoneal segment, but held within the adhesions so the subcutaneous tunnel was in direct communication with the peritoneal cavity; (iv) the proximal Dacron cuff was located about 3 cm inside the wall, within the ileal loops, to which it adhered; release of the cuff enabled evacuation of an abscess containing about 50 ml of pus with the same appearance as that observed on the dome of the bladder; (v) all the bacteriological cultures, including those for Mycobacterium tuberculosis (direct, gene-amplification and culture) yielded negative results; (vi) the biopsy findings (Dr N. Topley, Cardiff) pointed to chronic peritonitis with hyaline vascular lesions and complete mesothelial desquamation.

Comment.

An allergic reaction to dextrose polymers seems unlikely because the symptoms emerged after 7 months of Icodextrin use, because the initial cytology showed a marked predominance of neutrophils and not eosinophils or lymphocytes, and because some dialysis procedures with Icodextrin did not yield cloudy drainage fluid, while the pain and mild fever persisted following discontinuation of Icodextrin administration. We did not observe any concomitant skin or other reaction.

Icodextrin use could have affected the peritoneum through a toxic mechanism because the signs and symptoms developed 7 months after initiation of Icodextrin use and because pain was only markedly alleviated following discontinuation of Icodextrin, but the patient remained in a sub-febrile condition for some time afterwards. The APEX time of 46 min determined in October 1997 during the first few days of Icodextrin treatment suggested that the function of the peritoneal membrane was initially sufficient and normal, while the subsequent clinical course with loss of the ultrafiltration reflects degradation of that membrane. But, against this toxic hypothesis, the five Icodextrin batches used by the patient were also supplied to other patients without other complaints. An intact bag from three batches (samples from the other two batches were no longer available) was forwarded to Dr Topley for in vitro investigation for cytotoxicity. The results were negative.

Another more attractive explanation results from the findings of the last laparotomy. The surgery conducted in June 1996 probably led to the multiple adhesions of the omentum, ileal loops, and anterior parietal peritoneum, along with those in the Douglas' cul-de-sac. We cannot exclude the possibility that a peritoneal infection, attenuated by antibiotics, contributed to development of the adhesions. The abscess located on the dome of the bladder, in a totally buttressed zone excluded from the residual peritoneal cavity, may have been a sequela. The remodelling of the peritoneal cavity with zones excluded by multiple adhesions and poor catheter positioning incompatible with complete drainage of the cavity were responsible for an increase of ‘peritoneal dead space’. In addition, the Dacron cuff located in the ileal loops no longer ensured occlusion of the subcutaneous tunnel and any infection of the orifice could have readily contaminated the peritoneal space with infection hidden by antibiotics. This was confirmed by the presence of pus along the length of the catheter. In January 1998, infection of the orifice by Staphylococcus non-aureus was observed, and in April 98, was followed by a very probable chronic infection of the emergence site, since granulation tissue formation was noted.

Thus, we suggest that these drainage disorders that mimicked aseptic peritonitis were not directly related to Icodextrin, but to the marked ultrafiltration that it induces (more than that induced by glucose solution) in a residual peritoneal cavity full of adhesions and compartments. Abdominal pain and cloudy fluid were caused by the distension of this cavity that enabled lavage of purulent zones. This hypothesis is supported by the daytime pain that increased in the afternoon under Icodextrin and fell overnight during machine dialysis using smaller volumes, and by the resolution of the pain following discontinuation of Icodextrin.





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