Acute primary abdominal compartment syndrome due to Clostridium difficile induced toxic megacolon: a case report and review of the literature

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are increasingly recognized as causes of significant mortality and morbidity over the past decades [1]. Intra-abdominal pressure (IAP) is defined as the steady-state pressure concealed within the abdominal cavity and is affected by the volume of solid organs/hollow viscera, ascites, blood or other space-occupying lesions in combination with conditions that limit the expansion of the abdominal wall (e.g., edema). IAP is measured through a bladder catheter or nasogastric tube (Figure 1). IAH, defined as a sustained increase in IAP equal to or above 12 mm Hg (2 kPa), has numerous deleterious effects on end-organ function within and outside the abdominal cavity [2]. Detrimental consequences of IAH are reduced visceral perfusion and bowel ischemia, as well as decreased renal function due to transmission of elevated IAP on the kidney parenchyma and vascular structures leading to reduced arterial inflow and venous outflow. Reduced preload leads to activation of the renin-angiotensin-aldosterone system, further decreasing urine output [3]. Furthermore, IAH leads to elevated intrathoracic pressure, causing reduced venous return and cardiac preload, reduced end diastolic volumes and increased afterload. All these factors result in a decrease in cardiac output, leading to further organ failure. IAH can even worsen intra-cranial hypertension due to reduced cerebral venous return. It is clear that through these different mechanisms, ACS can lead to organ dysfunction and eventually death when left untreated [4]. Figure 2 summarizes the effects of IAH on end-organ function.
ACS is defined as a sustained increased IAP > 20 mm Hg (> 3 kPa) with associated new organ failure and can be primary or secondary in origin (Table 1). The incidence of ACS in a mixed population of critically ill patients is estimated to be around 10–35% [5]. Average mortality of ACS is estimated to be around 50% [6]. Patients with ACS are often very ill, and organ dysfunction may be incorrectly ascribed to the progression of the primary illness. Furthermore, symptoms, clinical findings and imaging are insufficient or aspecific to diagnose ACS [7]. We present the case of a 54-year-old man with primary ACS [8] to emphasize the importance of early recognition of ACS since early therapy leads to improved organ function and survival, followed by a review of the present literature.

Case presentation

A 54-year-old man with a history of acute mye­loid leukemia (AML), in complete remission after cytosine arabinoside therapy, was admitted to the Intensive Care Unit from the hematology ward (ZNA Stuiven­berg) because of progressive signs of shock. This case has been previously described in part [8]. At admission, he was awake but agitated with a Glasgow Coma Scale (GCS) of 14/15 (E4V4M6), blood oxygen saturation was 93% under oxygen therapy of 8 liters per minute with a respiratory rate of 32 per minute and hypoventilation of both lung bases. Blood pressure was 95/50 mm Hg with sinus tachycardia of 130 bpm with a pale aspect and a prolonged capillary refill time of 4 seconds. Central venous pressure (CVP) was 20 mm Hg (3 kPa).
There was significant abdominal distention, diffusely painful at palpation without noticeable peristalsis. The most remarkable laboratory results were an acute kidney injury with creatinemia of 1.95 mg dL-1, urea of 80 mg dL-1, highly elevated inflammatory parameters and normochromic anemia of 8.9 γ dL-1. Lactate was only slightly elevated at 2.8 mmol L-1 at admission. The IAP at admission was 20 mm Hg (3 kPa). Despite aggressive fluid resuscitation, hypotension persisted with rising lactate levels and the patient developed progressive respiratory failure, after which he was sedated and intubated. Furthermore, the patient became oliguric with diuresis of < 0.5 mL kg-1 h-1. Urgent bedside echocardiography showed low output with an estimated left ventricular ejection fraction of 30%, a mitral regurgitation of 2–3/4, a left ventricular end-diastolic pressure (LVEDP) of 25 mm Hg (3 kPa) and a dilated inferior vena cava of 21 mm but with respiratory variation. Inotropics (dobutamine) and vasopressors (norepinephrine) were initiated together with further fluid resuscitation. A computed tomography (CT) scan of the abdomen showed a dilated cecum of 16 cm, a diffusely thickened colon wall (4–6 cm), air in the cecum wall and extensive ascites (Figure 3). Given an IAP of 20 mm Hg (3 kPa), new onset organ failure (oliguria) and presence of extensive colitis on CT the diagnosis of acute primary ACS was made. Urgent surgical decompression was performed, and confirmed ACS and cecal hypoperfusion. Temporary abdominal closure (TAC) was performed with a Bogota bag. Stool cultures showed a toxin-producing Clostridium difficile; abdominal fluid cultures grew vancomycin-resistant
Enterococcus and Candida infection, after which antibiotherapy was adapted to meropenem, fluconazole, and linezolid. Immediately after abdominal decompression, urine output increased, and the need for vasopressors decreased. However, on the next day, there was ventilatory failure (increasing paCO2), hypotension despite high dose vasopressors and again a drop in urine output. Because of rising IAP despite the open abdomen urgent surgical reassessment of the abdomen was made, showing severe transmural colitis, and a total colectomy was performed with a VAC dressing as TAC. Afterwards, preload and cardiac output increased as well as urine output, followed by normalization of IAP and lactate levels. On day 5, the patient developed acute respiratory distress syndrome (ARDS), as shown in Figure 4, for which lung protective ventilation was initiated in combination with de-resuscitation, initially with hyperoncotic albumin 20% and diuretics and afterwards with continuous veno-venous hemofiltration (CVVH) with ultrafiltration. On day seven the patient was extubated, and he was discharged from the ICU to the hematology ward on day 10. Figure 5 shows the evolution of the physiologic parameters.

Methods

A systematic search of PubMed and NCBI databases was performed for studies describing cases of Clostridium difficile infection (CDI) causing toxic megacolon and primary ACS. Search terms used were: ‘clostridium difficile’, ‘toxic megacolon’, ‘abdominal compartment syndrome’, single or in combination. Related articles were used to broaden the search and citations were scanned for relevance. The last search was performed for March 2019.

Results

We found 18 case reports relevant to the subject. Table 1 summarizes the 19 cases of CDI with ACS. The male/female ratio was 12/7, and there were 3 children. The mean age was 48.7 ± 23.5 years. The reason for admission was sepsis in 6 patients (of whom 2 were immunocompromised after heart transplant and with cystic fibrosis), trauma in 2 (one with severe burns), postoperative in 4 (one heart transplant, one nephrectomy), enterocolitis in 5, pregnancy in 1 and abdominal complaints after topical antibiotics in 1. Three patients did not develop diarrhea. Five patients developed diarrhea on average 5.8 ± 5.1 (median 4, range 1–14) days before hospital admission while 7 patients developed diarrhea on average after 10 ± 19.6 (median 3, range 0–54) days during admission. The mean IAP (measured in 6 patients, including ours) was 29.2 ± 11 (range 20–50) mm Hg (3–7 kPa). Treatment consisted of (a combination of) vancomycin (orally in 10 and rectal enemas in 4), metronidazole (orally in 4 and IV in 11), and surgical intervention (with decompressive laparotomy) in 12 (surgery was refused in 2). Neostigmine was added as adjuvant treatment in 1 patient while fecal transplantation was performed in 2. Three patients died (15.8%).

Discussion

Incidence of C. difficile colitis has been increasing in recent years [9] and severe C. difficile infection (CDI) can cause severe morbidity and mortality. Severe CDI is defined as fulminant colitis, toxic megacolon or perforation and is thought to occur in 8% of cases, with an estimated mortality of 30–80% [10]. Toxic megacolon often leads to IAH. We describe a case of IAH leading to abdominal compartment syndrome with the need for exploratory laparotomy and temporary abdominal closure with a Bogota bag. Despite the presence of an open abdomen, the patient developed ACS, for which he subsequently received total colectomy. To our knowledge, this is the first case report which describes a new ACS despite decompressive laparotomy (excluding the trauma setting). We performed a review of current literature for case reports of abdominal compartment syndrome in the setting of CDI.
Since the symptoms and clinical and radiological findings of IAH are not very specific and patients with ACS are usually very ill, there can be a delay in diagnosis and adequate treatment. Severe CDI with toxic megacolon can occur without diarrhea and thus diagnosis is sometimes postponed [8]. Failure to recognize IAH before the development of ACS causes tissue hypoperfusion, which may lead to multisystem organ failure, and potentially death. Monitoring IAP for early detection of IAH and ACS in critically ill patients not only can be helpful in diagnosis, leading to early intervention and an improved outcome for the patient, but also in management (e.g., oliguria due to ACS should not lead to more aggressive fluid resuscitation, but to fluid removal or decompression). Since treatment can improve organ dysfunction, it is essential that diagnosis is considered in the appropriate clinical situation. Studies show that ACS will not develop under 10 mm Hg (1 kPa), while ACS is mostly sure at an IAP of 25 mm Hg (3 kPa) or above [5]. ACS should be suspected when IAP is in the grey zone in between, and there is new onset organ failure. Acute kidney injury (AKI) with oliguria is often one of the first findings of ACS as AKI is considered as the canary in the coalmine for IAH. The most important step in the treatment of IAH/ACS is prevention or early recognition through IAP monitoring.
Risk factors for development of severe CDI are recent antibiotic therapy and an immunosuppressed status. Two case reports describe the development of toxic megacolon due to CDI after administration of topical antibiotics in burn patients [11, 12]. Clindamycin, cephalosporins and fluoroquinolones are the most common provoking antibiotics [13].
Treatment of IAH consists of measures to increase abdominal wall compliance, amongst other treatment modalities. Careful fluid management is essential to avoid fluid overload due to aggressive fluid resuscitation, which may lead to increased IAP due to second and third space fluid accumulation. Therefore, advanced hemodynamic monitoring (e.g. with transpulmonary thermodilution) should be performed in these patients to guide fluid, inotrope and vasopressor therapy. Barometric based assessment of intravascular volume (such as CVP) has been shown to be erroneous in IAH [14]; volumetric-based parameters (such as global end-diastolic volume) are better to guide fluid therapy [15]. The evacuation of intraluminal fluid contents (through a nasogastric or rectal tube) and percutaneous drainage of intra-abdominal fluid collections have also been proposed to reduce IAP. Furthermore, administration of diuretics or even the use of renal replacement therapy with ultrafiltration (UF) in patients with profound capillary leak are recommended to reduce IAP in hemodynamically stable patients. Dabrowski et al. found that in septic shock patients continuous venovenous hemofiltration with net UF successfully reduced IAP [16]. However, it remains unknown whether strategies that target a neutral or even negative fluid balance may be correlated with improved clinical outcome [17].
The most effective and definite treatment (in the setting of primary ACS), with the most supporting evidence, is urgent abdominal decompression through median laparotomy [18]. Though several techniques exist, some form of temporary abdominal closure should be performed. Urgent decompression should be considered in patients with ACS refractory to conservative medical measures or patients with an IAP > 20 mm Hg (3 kPa) and worsening organ failure. This decision should be made on an individual basis with an assessment of risks and benefits for the patient. Even after decompression, monitoring of IAP should be continued, since ACS can still occur in patients with an open abdomen and temporary closure and should warrant new surgical exploration (as in our case presented herein). Patients undergoing decompressive laparotomy should have early (within 7 days), or at least same-hospital-stay abdominal fascial closure. Early fascial closure is associated with reduced mortality and complications [19].
Although there are no current guidelines for the management of severe CDI, most authors suggest initial conservative management with IV metronidazole and vancomycin enterally [20]. There is no consensus as to whether vancomycin should be administered orally or rectally. Some authors suggest that this should depend on the most dominantly affected part of the intestine (enema for transverse and distal colon, oral route for ascending colon or small bowel). We found 1 case report with small bowel disease related to CDI [21]. The role of newer agents (e.g. fidaxomicin) has yet to be determined. Two case reports describe treatment with fecal microbiota transplantation, with full recovery [22, 23].
For patients with severe CDI combined with selected host factors (age > 70 years) and laboratory test results (WBC > 15 G L-1; creatinine > 1.5 × baseline; albumin < 3 γ L-1) and the clinical triad of abdominal pain, abdominal distension, and diarrhea, or toxic megacolon, surgical management is indicated. The prior standard procedure was colectomy, but more recently an alternative procedure has been a diverting ileostomy with colonic lavage using vancomycin and metronidazole [24].

Conclusions

In conclusion, IAP should be monitored early in critically ill patients at risk for IAH, so that measures can be undertaken to prevent ACS. The incidence of ACS in CDI is low, with only 19 cases reported in the literature. We recommend monitoring of IAP in patients with toxic megacolon caused by CDI. If ACS occurs, hemodynamic monitoring should be used to guide fluid therapy through volumetric-based parameters to avoid fluid overload and fluid accumulation. Early surgical decompression with TAC should be performed if there is progressive organ failure under medical management. Early fascial closure should be attempted if the outcome is favorable.

Acknowledgements

1. Special thanks to Rita Jacobs for reading the final manuscript and suggesting some minor edits.
2. Financial support and sponsorship: none.
3. Conflicts of interest: none.

References

1. Malbrain ML, Cheatham ML, Kirkpatrick A, et al. Results from the International Conference of Experts on Intra-abdominal Hyper­tension and Abdominal Compartment Syndrome. I. Definitions. Intensive Care Med 2006; 32: 1722.
2. Schein M, Ivatury R. Intra-abdominal hypertension and the abdominal compartment syndrome. Br J Surg 1998; 85: 1027.
3. Malbrain ML, Chiumello D, Pelosi P, et al. Prevalence of intra-abdominal hypertension in critically ill patients: a multicentre epidemiological study. Intensive Care Med 2004; 30: 822.
4. Vidal MG, Ruiz Weisser J, Gonzalez F, et al. Incidence and clinical effects of intra-abdominal hypertension in critically ill patients. Crit Care Med 2008; 36: 1823.
5. Malbrain ML, Chiumello D, Cesana BM, et al. A systematic review and individual patient data meta-analysis on intra-abdominal hypertension in critically ill patients: The wake-up project. World initiative on Abdominal Hypertension Epidemiology, a Unifying Project (WAKE-Up!). Minerva Anaesthesiology 2014; 80: 293-306.
6. Malbrain ML, Chiumello D, Pelosi P, et al. Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological study. Crit Care Med 2005; 33: 315.
7. van Mook WN, Huslewe-Evers RP, Ramsay G. Abdominal compartment syndrome. Lancet 2002; 360: 1502.
8. Malbrain M, De laet I, Willems A, Van Regenmortel N, Schoonheydt K, Dits H. Localised abdominal compartment syndrome: bladder-over-gastric pressure ratio (B/G) as a clue to diagnosis. Acta Clin Belg 2010; 65: 98-106. doi: 10.1179/acb.2010.021.
9. Oud L. Intra-abdominal hypertension in fulminant Clostridium difficile infection – an under-recognized treatable complication. Med Sci Monit 2010; 16: 110-113.
10. Bhangu A, Nepogodiev D, Gupta A, Torrance A, Singh P, West Midlands Resaerch Collaborative. Systematic review and meta-analysis of outcomes following emergency surgery for Clostridium Difficile Colitis. Br J Surg 2012; 99: 1501-1513.
11. Tan CB, Shah M, Ahmed S, Freedman L, Rizvon K, Mustacchia P. Toxic megacolon from fulminant Clostridium difficile infection induced by topical silver sulphadiazine. BMJ Case Rep 2012; 2012: bcr2012006460.
12. Jennings L, Hanumadass M. Silver sulfadiazine induced Clostridium difficle toxic megacolon in a burn patient: a case report. Burns 1998; 24: 676-679.
13. Sayedy L, Kothari D, Richards R. Toxic megacolon associated Clostridium difficile colitis. World J Gastrointest Endosc 2010; 16: 293-297.
14. Cullen DJ, Coyle JP, Teplick R, Long MC. Cardiovascular, pulmonary, and renal effects of massively increased intra-abdominal pressure in critically ill patients. Crit Care Med 1989; 17: 118.
15. 15.Morken J, West MA. Abdominal compartment syndrome in the intensive care unit. Curr Opin Crit Care 2001; 7: 268.
16. Dabrowski W, Kotlinska-Hasiec E, Schneditz D, et al. Continuous veno-venous hemofiltration to adjust fluid volume excess in septic shock patients reduces intra-abdominal pressure. Clin Nephrol 2014; 82: 41-50.
17. Kirkpatrick AW, Roberts DJ, De Waele J, et al; Pediatric Guidelines Sub-Committee for the World Society of the Abdominal Compartment Syndrome. Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Intensive Care Med 2013; 39: 1190-1206.
18. De Waele JJ, Kimball E, Malbrain M, et al. Decompressive laparotomy for abdominal compartment syndrome. Br J Surg 2016; 103: 709.
19. An G, West MA. Abdominal compartment syndrome: a concise clinical review. Crit Care Med 2008; 36: 1304.
20. Shaikh N, Kettern MA, Hanssens Y, Elshafie SS, Louon A. A rare and unsuspected complication of Clostridium Difficile infection. Intensive Care Med 2008; 34: 963-966.
21. Thai H, Guerron AD, Bencsath KP, Liu X, Loor M. Fulminant Clostridium difficile enteritis causing abdominal compartment syndrome. Surg Infect 2014; 15: 821-825.
22. Costello SP, Chung A, Andrews JM, Fraser RJ. Fecal microbiota transplant for clostridium difficile colitis-induced toxic megacolon. Am J Gastroenterol 2015; 110: 775-777.
23. Gweon T, Lee KJ, Kang DH, et al. A case of toxic megacolon caused by Clostridium difficile infection ad treated with fecal microbiota transplantation. Gut and Liver 2015; 2: 247-250.
24. Bartlett JG. Clostridium difficile Infection. Infect Dis Clin North Am 2017; 31: 489-495. doi: 10.1016/j.idc.2017.05.012.
25. Mann A, McCague A, Lalezarzadeh F. Surgical outcome of community-acquired Clostridium difficile colitis presenting as toxic megacolon: case report. Surg Infect 2011; 12: 317-320.
26. Lorenzo CSV, Luis SF, Granados JMS, Ayestaran OA, Gomez de Quero Masia P, Salas EG. Fulminant pseudomembranous colitis and abdominal compartment syndrome. Pediatr Ther 2016; 6: 2.
27. Oguri N, Sakuraba A, Morikubo H, et al. Community-acquired fulminant colitis caused by binary toxin-producing Clostridium difficile in Japan. Clin J Gastroenterol 2019; 12: 325-329. doi: 10.1007/s12328- 019-00949-z.
28. Cheng-Ming M, Chien-Chig. Toxic Megacolon with abdominal compartment syndrome. J Trauma 2011; 71: 44.
29. Castillo A, Lopez J, Panadero E, Cerda J, Padilla B, Bustinza A. Conservative surgical treatment for toxic megacolon due to Clostridium difficile infection in a transplanted pediatric patient. Transpl Infect Dis 2012; 14: 234-237.
30. Kerstens J, Diebels I, de Gheldere C, Vanclooster P. Blowhole colostomy for clostridium difficile-associated toxic megacolon. Case Rep Surg 2016; 2016: 5909248.
31. Dobson G, Hickey C, Trinder J. Clostridium difficile colitis causing toxic megacolon, severe sepsis and multiple organ dysfunction syndrome. Intensive Care Med 2003; 29: 1030. doi: 10.1007/s00134-003-1754-7.
32. Patel A, Gosset J, Benton T, et al. Fulminant Clostridium difficile toxic megacolon in a pediatric heart transplant recipient. Pediatr Transplant 2012; 16: 30-34.
33. Candiotto A, Pascoli I, Gritti A, Busato, Dal Pozzo G. Toxic megacolon complication a Clostridium difficile infection in a pregnant woman. J Med Microbiol 2010; 59: 124-126.
34. Griniatsos J, Dimitriou N, Tyritzis S, Papps P, Sougioultzis S, Stravodimos K. Toxic megacolon due to fulminant Clostridium Difficile colitis. Acta Gastroenterologica Belgica 2011; 75: 359-360.
35. Desie N, Willems A, De Laet I, et al. Intra-abdominal pressure measurement using the FoleyManometer does not increase the risk for urinary tract infection in critically ill patients. Ann Intensive Care 2012; 2 (Suppl 1): S10. doi: 10.1186/2110-5820-2-S1-S10.
36. Regli A, Pelosi P, Malbrain M. Ventilation in patients with intra-abdominal hypertension: what every critical care physician needs to know. Ann Intensive Care 2019; 9: 52. doi: 10.1186/s13613-019-0522-y.