Acute bowel ischemia following spinal surgery.

Abstract: Acute mesenteric ischemia is a morbid condition that may be difficult to diagnose due to nonspecific nature of its symptoms. To our knowledge, such a complication has not previously been reported after spinal surgery via the posterior approach. We describe the case of a 43-year-old woman who developed acute mesenteric ischemia several days after a surgical procedure for a lumbar spondylolisthesis via the posterior route. This chronic course is suggestive for venous intestinal ischemia. Prone position and hypotension during the procedure may have favored blood stasis and mesenteric vein occlusion in this patient with an inherited hypercoagulable state.

Key Words: acute mesenteric ischemia, venous intestinal ischemia, spinal surgery

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The frequency of complications during spinal surgery seems to be very high, ranging from 3.6 to 53%. (1) Complications can be related to anesthesia, patient positioning and surgical technique. The posterior approach to the spine is generally considered less prone to complications than the anterior method, (1) as it usually results in only minimal soft tissue damage. (1) However, major complications such as vascular injury have been reported. (2) Nevertheless, to our knowledge, intestinal ischemia has not been described following spinal surgery via the posterior approach.

Case Report

A 43-year-old Moroccan woman underwent spinal surgery via a posterior approach for an L5-S1 spondylolisthesis. Her medical history was only remarkable for moderate asthma, untreated hypercholesterolemia and hip replacement 9 years previously. Her blood pressure was 135/80 mm Hg. There was no personal or family history of venous thrombosis. Preoperative coagulation parameters, including prothrombin time, aPTT, INR and fibrinogen were normal.

The patient was prone positioned on the orthopaedic table, leaving her abdomen absolutely free of compression. Elastic compression stockings were applied to her legs. After induction by propofol and midazolam, anesthesia was maintained by sevoflurane and sufentanil. Instrumental arthrodesis (CCD TITANE) was then performed via a median posterior route. Moderate hypotension, with a systolic blood pressure of 100 mm Hg, was maintained during the 2 hour and 40 minute procedure to minimize blood loss. Recovery was uneventful. Deep veinous thrombosis (DVT) prevention was started postoperatively using elastic compression stockings and enoxaparin (4,000 IU/d). The patient could eat by the second hospital day (HD) and only moved on the 5th HD without any complaint.

By the 9th HD, she began complaining of nausea and vague abdominal pain. Physical examination did not disclose any abnormality. The body temperature was normal as were the laboratory findings. On the following days, the pain became so intense that it reduced food intake and limited walking. Profuse diarrhea appeared on the 23rd HD. Repeated laboratory tests performed-during this period only disclosed moderate leucocytosis. Electrolytes, liver enzymes, amylase, lipase, fibrinogen, coagulation tests and renal function were within normal limits. Computed tomography and ultrasound examination of the abdomen were normal. Stool examination and blood cultures remained sterile. Nifuroxazid and paracetamol were prescribed, but the patient's status continued to deteriorate and by the 24th hospital day, she ceased eating.

On the 26th HD, laparotomy was performed revealing massive intestinal ischemia with necrosis extending from the proximal jejunum to the middle of the transverse colon. Both mesenteric vein and superior mesenteric artery appeared occluded at examination. Intestinal resection was performed, leaving only 40 cm of viable small bowel. A Doppler of the lower limbs as well as an echocardiogram did not show any abnormality. Total parenteral nutrition and heparin anticoagulation were instituted and the patient made a progressive recovery. Extensive analysis for an underlying hypercoagulable state only revealed combined heterozygosity for G20210A gene expression and C677T methylene tetrahydrofolate reductase (MTHFR) mutation. Molecular testing was performed by polymerase chain reaction (PCR) and fluorescence monitoring using hybridization probes. Sensitivity and specificity for detection of these mutations are as high as 99.9. The patient was discharged on warfarin. Intestinal continuity was re-established six months later, and 15 months after spinal surgery, the patient remains in good health.

Discussion

Acute mesenteric ischemia is a morbid condition that remains difficult to diagnose due to the nonspecific nature of the symptoms during the early phase of the disease process. (3) Historically, it portends a poor prognosis, with mortality rates ranging from 60 to 100%. (3) Early diagnosis, resection of infarcted bowel, restoration of blood flow, supportive intensive care, and the cause of bowel ischemia are among the factors that influence the mortality rate. (4) Indeed, patients with an acute thrombosis of the splanchnic veins may have a better chance of survival than those with arterial ischemia. (3,4) Differentiating between these two causes, however, remains a difficult challenge due to the similarity between the symptoms of arterial (AII) and venous intestinal ischemia (VII). (3) Like other types of venous thrombosis, the etiology of VII should be understood in term of Virchow triad of stasis, vessel injury, and hypercoagulable state. Indeed, particular predisposing conditions such as previous abdominal surgery, malignancies, immobilization, oral contraceptive use, and elevated cardiolipin antibodies have been associated with VII. (5,6) Few reports have also attributed VII to Leiden factor V or prothrombin gene mutation. (6-8)

Pathophysiological studies have shown that infarction of the intestine, even if the superior mesenteric vein is completely occluded, rarely occurs unless the collateral vessels (venous arcades and vasa recta) are involved. (5) Time from onset of the symptoms to diagnosis may then be longer than in cases of AII. (3,8) The most common initial symptom is abdominal pain which is vague and out of proportion to the physical findings. (3,5) The frequency of nausea, vomiting and diarrhea are similar for AII and VII, but hematemesis and hematochezia, although rare, are only encountered in cases of VII. (3,5)

Except for the recent spinal surgery, our patient had no apparent acquired risk factors for venous thrombosis or VII. (5,6,9) Moderate hypotension and prone position during surgery may have favored an alteration in blood flow with subsequent stasis and/or a vessel injury. Screening for inherited causes of venous thrombosis revealed a substitution of adenine for guanine at nucleotide 20,210 in the 3'-untranslated region of the prothrombin gene (G20210A). For unknown reasons, this mutation is associated with an increased level of plasma prothrombin, an effect that promotes the generation of thrombin and impairs the inactivation of activated factor V by activated protein C. (9) A single copy of this variant (heterozygote) is linked to a three-fold increased risk of venous thrombosis. A homozygous mutation further increases this risk. (6) This hereditary thrombophilic disorder has also been established as a risk factor for cerebral vein thrombosis and myocardial infarction, particularly when associated with other predisposing conditions. (5-7,9,10)

The role of the MTHFR mutation, although questioned, may also be advocated. (10,11) One of the most common genetic defects of homocysteine metabolism is a mutation in the enzyme methylene tetrahydrofolate reductase (MTHFR). This enzyme is involved with folate metabolism, catalyzing the reduction of 5,10-methylenetetrahydrofolate to 5-methyltet-rahydrofolate. Folate is a cofactor in remethylation of homocysteine. Without it, homocysteine levels in the plasma increase. The molecular basis for this mutation was shown to be a C-to-T transition at base position 677, which substitutes valine for an alanine. It is associated with reduced enzyme activity and elevated total homocysteine levels in serum or plasma, which in turn increases the risk of venous thrombosis. (9) The relation of these inherited thrombophilic states with mesenteric and portal vein thrombosis has been suggested. (6,12) Indeed, Amitrano et al (12) reported a high prevalence of prothrombin G20210A and MTHFR mutations in patients with acute mesenteric vein thrombosis. Due to these predisposing factors, DVT prevention with enoxaparin, even if it was maintained throughout the hospitalization period, may have been insufficient in our patient.

The first symptoms appeared 9 days after surgery and lasted more than 15 days before diarrhea appeared. Although intriguing, this "chronic" course is suggestive of VII. (3,5) Laparotomy, performed on the 29th day post surgery, could not differentiate between AII and VII due to the occlusion of both venous and arterial vessels. Indeed, it is well established that differentiating arterial from venous occlusion late in the process of VII is impossible. (5) All these conditions led us to believe that our patient really had a course of VII following spinal surgery, even if the time course between surgery and the event was unusually long.

To our knowledge, our case is the first report of such a complication following spinal surgery and/or prone position, even in patients with blunt trauma and prolonged prone ventilation. (1,2,13) Clinicians should keep in mind that only early consideration of the diagnosis of acute bowel ischemia and a detailed knowledge about its pathogenesis, in patients with combined nonspecific clinical, laboratory and radiological findings could improve the prognosis. (5,14)

Conclusion

Although intriguing, the hospital course of our patient suggests that VII is a possible complication of spinal surgery via the posterior route. A long bedrest, prone position and/or hypotension may have favored stasis which in turn resulted in a mesenteric vein occlusion in a patient with an unknown inherited thrombophilia. Prevention of such a complication remains difficult, but DVT prophylaxis with enoxaparin before surgery may have reduced the risk of thrombosis. Clinicians should consider mesenteric ischemia when faced with a patient having abdominal pain with a negative workup for its common causes. Liberal use of abdominal CT and early consideration of anticoagulation and/or thrombolytic therapy, provided that signs of intestinal ischemia are absent, may decrease morbidity and mortality from VII.

References

1. Knop C, Bastian L, Lange U, et al. Complications in surgical treatment of thoracolumbar injuries. Eur Spine J 2002; 11:214-226.

2. Papadoulas S, Konstantinou D, Kourea H, et al. Vascular injury complicating lumbar disc surgery: a systematic review. Eur J Vase Endovasc Surg 2002;24:189-195.

3. Endean ED, Barnes SL, Kwolek CJ, et al. Surgical management of thrombotic acute intestinal ischemia. Ann Surg 2001;233:801-808.

4. Klempnauer J. Grothues F. Bektas H. et al. Long-term results after surgery for acute mesenteric ischemia. Surgery 1997;121:239-243.

5. Hassan HA, Raufman JP. Mesenteric venous thrombosis. South Med J 1999;92:558-562.

6. Al-Juburi A. Scott MA, Shah HR, et al. Heterozygosity for factor V Leiden and G20210A prothrombin genotypes in a patient with mesenteric vein thrombosis. Dig Dis Sci 2002;47:601-606.

7. Heresbach D, Pagenault M, Gueret P, et al. Leiden factor V mutation in four patients with small bowel infarctions. Gastroenterology 1997;113:322-325.

8. Divino CM, Park IS, Angel LP. et al. A retrospective study of diagnosis and management of mesenteric vein thrombosis. Am J Surg 2001;181:20-23.

9. Seligsohn U. Lubetsky A. Genetic susceptibility to venous thrombosis. N Engl J Med 2001;344:1222-1231.

10. McGlennen RC, Key NS. Clinical and laboratory management of the prothrombin G20210A mutation. Arch Pathol Lab Med 2002;126:1319-1325.

11. Margaglione M, D'Andrea G, D'Addedda M, et al. The methylenetetrahydrofolate reductase TT677 genotype is associated with venous thrombosis independently of the coexistence of the FV Leiden and the prothrombin A 20210 mutation. Thromh Haemost 1998;79:907-911.

12. Amitrano L. Brancaccio V, Guardascione MA, et al. High prevalence of thrombophilic genotypes in patients with acute mesenteric vein thrombosis. Am J Gastroenterol 2001;96:146-149.

13. Offner PJ, Haenel JB, Moore EE, et al. Complications of prone ventilation in patients with multisystem trauma with fulminant acute respiratory distress syndrome. J Trauma 2000;48:224-228.

14. CT of acute bowel ischemia. Radiology 2003;226:635-650.

Reality leaves a lot to the imagination.
--John Lennon

Ali Mofredj, MD, Ibrahim Traore, MD, Brahim Beldjoudi, MD, Djelloul Aoula, MD, and Raouf Douiri, MD

From the Service de Reanimation and the Service de Chirurgie, Hopital Laennec, Creil, France.

Reprint requests to Ali Mofredj, Service de Reanimation, Centre Hospitalier General, 207, Avenue Julien Fabre. 13300 Salon de Provence, France. Email: [e-mail]

Accepted June 8, 2005.

RELATED ARTICLE: Key Points

* Venous intestinal ischemia is a morbid condition that remains difficult to diagnose due to the absence of specific symptoms.

* Only a "chronic course" of the disease may differentiate venous from arterial intestinal ischemia.

* The etiology of venous intestinal ischemia should be understood in terms of Virchow triad of stasis, vessel injury, and a hypercoagulable state.

* Inherited hypercoagulable states, such as prothrombin gene and MTHFR mutation, are currently recognized as common predisposing conditions.

* Early consideration of the diagnosis and a detailed knowledge about its pathogenesis could improve the prognosis.