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Journal of Obstrectic Anaesthesia and Critical Care
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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 8  |  Issue : 2  |  Page : 108-111

Anesthetic management of parturient with hyperhomocysteinemia for cesarean section


Department of Anesthesiology and Critical Care, Jaipur Golden Hospital, New Delhi, India

Date of Web Publication3-Oct-2018

Correspondence Address:
Dr. Radha Gupta
Department of Anesthesiology and Critical Care, Jaipur Golden Hospital, Rohini, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/joacc.JOACC_44_17

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  Abstract 


Hyperhomocysteinemia is due to genetic and acquired changes in the metabolism of homocysteine. It is associated with an increased risk for vascular occlusive disease and thrombosis. Because methylene tetrahydrofolate reductase abnormality is a genetic disorder and hyperhomocysteinemia along with pregnancy in women further aggravates the risk of thrombosis; therefore, these patients undergo antepartum anticoagulant treatment with low molecular weight heparin. These patients pose a unique challenge to anesthetist, when it comes to choosing a type of anesthesia. Neuraxial anesthesia techniques may be relatively contraindicated in anticoagulated patients and nitrous oxide may exacerbate the condition, by inhibiting the conversion of homocysteine to methionine. In this study, we intend to discuss the anesthetic implications and management of a pregnant patient with hyperhomocysteinemia undergoing cesarean section.

Keywords: Anticoagulants, general anesthesia, hyperhomocysteinemia, nitrous oxide, methylene tetrahydrofolate reductase, pregnancy


How to cite this article:
Gupta R, Bhalla S, Prakash S, Upadhyay N. Anesthetic management of parturient with hyperhomocysteinemia for cesarean section. J Obstet Anaesth Crit Care 2018;8:108-11

How to cite this URL:
Gupta R, Bhalla S, Prakash S, Upadhyay N. Anesthetic management of parturient with hyperhomocysteinemia for cesarean section. J Obstet Anaesth Crit Care [serial online] 2018 [cited 2018 Dec 16];8:108-11. Available from: http://www.joacc.com/text.asp?2018/8/2/108/242627




  Introduction Top


Hyperhomocysteinemia, which is a risk factor for recurrent pregnancy loss, is acquired as a result of deficiencies of vitamin B12 and folate B9 or related to a hereditary defect within the methionine-homocysteine pathway or it might be [Figure 1] oxidative damage, vascular smooth muscle proliferation, promotion of platelet activation, and aggregation. Disruption of normal procoagulant balance favoring thrombosis associated with the increase in plasma level of homocysteine is responsible for higher risk of thromboembolic events.[1] Physiological changes in pregnancy also induce a state of reactive hypercoagulability.[2] The risk of venous thromboembolism is increased 5–10-fold during pregnancy.[1] Furthermore, the association of pregnancy with thrombophilia is highly correlated with the occurrence of severe feto-maternal complications. For these reasons, the associations of thrombophilic state with the hypercoagulant state of the pregnancy lead to the recommendation of the anticoagulant treatment.
Figure 1: Metabolic pathway of homocysteine

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The association of hyperhomocysteinemia with pregnancy creates a particular anesthetic challenge because predisposition to hypercoagulation requires anticoagulant treatment to prevent thromboembolism on a continuous basis, which potentiates the risk of postregional anesthesia hematoma. General anesthesia with nitrous oxide inhibits the conversion of homocysteine in methionine, which increases the risk of postanesthetic thrombosis.

The hypercoagulable state produced by homocysteinemia and anticoagulation therapy leads to a unique anesthetic circumstance that should be managed carefully. We are presenting a case report of a pregnant patient with hyperhomocysteinemia and the anesthetic implications and management presenting for emergency cesarean section.


  Case Report Top


A 29-year-old, G3P0A2 parturient at 35 weeks of gestation, American Society of Anesthesiologist (ASA) physical status II, 84 kg, 165 cm, with Mallampati class I airway, was admitted to hospital with complaints of leaking per vagina and history of hyperhomocysteinemia.

Hyperhomocysteinemia in our patient was diagnosed on screening for thrombophilia at 6 weeks of gestation, in view of past history of recurrent spontaneous abortions. She was genetically tested positive, for homozygous state for the C677T mutation at the level of methylene tetrahydrofolate reductase gene. During pregnancy, patient was begun and continued on daily dosage of enoxaparin 40 mg subcutaneously and aspirin 75 mg orally daily. Since the time of diagnosis, she was also started on daily doses of folic acid, vitamin B12, and B6. Her homocysteine level was 16 μmol/L (normal homocysteine level is <12 μmol/L at 6 months of period of gestation, and it is 4 μmol/L at 34 weeks of period of gestation).

Abdominal ultrasonography was done, which revealed oligohydramnios and loop of cord around the neck of fetus. In view of poor obstetric history, ultrasonographic report, and presence of leaking per vagina, patient was decided to be taken up for an emergency cesarean section. There was nothing abnormal found on physical and systemic examination of patient. Preoperative laboratory investigations revealed platelet count of 1.74 lacs/mm3, prothrombin time/international nromalized ratio – 15.5/1.06, BleedingTime/ ClottingTime – 2′30”/5′00”, Activated Prothrmobin Time – (test – 32.9; control – 32.0); clot retraction time – 50. Routine hematological and biochemical tests were within normal limits. Last meal was one glass of water 6 h back. The last dose of enoxaparin received was 4 h back, which was insufficient and unsafe time to proceed for subarachnoid block, therefore general anesthesia with rapid sequence induction was planned metoclopramide 10 mg and ranitidine 50 mg was given intravenously as antiaspiration prophylaxis before surgery.

On arrival to the operation theatre, after establishing the monitors, baseline parameters were noted. Pneumatic compression device was applied on both legs; 18 G peripheral intravenous (i.v.) cannula was inserted and good hydration was ensured throughout perioperative period to decrease the risk of perioperative thromboembolic complications. Patient was induced with thiopentone sodium 250 mg after preoxygenation for 3 min, tracheal intubation with 7.5 mm PVC tube was facilitated with applied cricoid pressure using succinylcholine 100 mg. Anesthesia was maintained with oxygen, air, and 0.8% isoflurane till the delivery of baby. Nitrous oxide was avoided. A male baby of 1.5 kg with APGAR score of more than 8 was delivered. Vecuronium was used for neuromuscular paralysis and fentanyl 100 μg was given for analgesia after delivery of the baby.

Vitals remained within normal limit throughout intraoperative period. After delivery of baby, oxytocin 25 units in 500 ml of normal saline was administered over an hour. Estimated blood loss was 500 ml and total fluid replaced was 2000 ml. Residual neuromuscular blockade was reversed with neostigmine 2.5 mg and glycopyrrolate 0.4 mg and the trachea was extubated. Patient was monitored in post anesthesia care unit for another 2 h. She was awake, pain free, and vitals were stable. The anticoagulant treatment was resumed with enoxaparin 40 mg once a day after 24 h of surgery and was advised to continue it for 6 weeks. She was discharged home after 4 days.


  Discussion Top


Homocysteinemia is a condition characterized by an elevation of homocysteine level in the blood. It has a prevalence of almost 5–15% of the general population. Plasma level of homocysteine was controlled by two distinct metabolic pathways.[3] Homocysteine is either degraded to cysteine by trans-sulfuration or recycled to methionine by remethylation [Figure 1].[4] Hyperhomocysteinemia is a risk factor for both arterial and venous thrombosis and also for abortion. Thus recommendations are to normalize the levels of homocysteine through adequate vitamin substitution as we have done in our case once the diagnosis of hyperhomocysteinemia was established. The disruption of any of the required enzymes or cofactors involved in the pathways of methionine are the primary cause of accumulation of homocysteine and its metabolite [Figure 1]. Either genetic predisposition and/or nutritional and environmental factors can lead to these conditions. 95% (most common) of the patients of hyperhomocysteinemia is caused by the deficiency of the cofactor pyridoxine (vitamin B6), folate, cobalamin (vitamin B12), or the enzyme CBS.[5]

Vitamin B supplements, folic acid, B6, B12, and anticoagulant treatment to prevent vascular thromboses comprises the conventional treatment for hyperhomocysteinemia.[6] Heparin compounds are the most preferred agent for anticoagulation in pregnancy because neither low-molecular weight heparin (LMWH) nor heparin crosses the placenta and therefore, both are considered safe for pregnancy.[7],[8] Women are often shifted to unfractionated heparin from LMWH at 36–37 weeks of gestation because of the advantage of shorter therapeutic half-life of unfractionated heparin.[3]

The choice of anesthesia (general/regional) to avoid secondary fetomaternal complications is controversial because of the involvement of hyperhomocysteinemia in the production of thrombotic events and recommendation of anticoagulant treatment throughout the pregnancy.[9] American Society of Regional Anesthesia and Pain Medicine convened its second Consensus Conference on Neuraxial Anesthesia and Anticoagulation in 2002 and concluded that subcutaneous (minidose) thromboprophylaxis with unfractionated heparin does not contraindicate the use of neuraxial anesthetic technique.[10] So, regional anesthesia can be performed safely, if the anticoagulant therapy is interrupted 8–12 h before the surgery and if the number of thrombocytes, activated partial thromboplastin time, international normalized ratio levels, and the activated X factor activity are within normal limits. We avoided regional anesthesia in our case because patient received last dose of LMWH just 4 h before and an emergency cesarean section was planned, so we went ahead with the general anesthesia for our patient.

If use of nitrous oxide is not involved, then general anesthesia is considered as a safe solution; as we did in our case and used air in place of nitrous oxide. N2O slows the conversion of homocysteine to methionine by irreversibly inhibiting methionine synthetase, which leads to an acute rise in the level of homocysteine and further reduction in the methionine levels.[11] N2O administration not only exacerbates homocysteinemia but also impairs endothelial function and promotes procoagulant activity, such as platelet adhesiveness, factor V activation, protein C inhibition, and prothrombin and plasminogen activator binding.[12],[13],[14] In a randomized prospective study, a rise of 12–24 μmol/L of postoperative plasma homocysteine levels in patients without hyperhomocysteinemia after N2O anesthesia is observed.[14]

Zanardo et al.[15] observed significantly higher levels of plasma homocysteine levels in both the maternal and umbilical venous plasma of women who delivered vaginally by measuring the plasma homocysteine levels in 50 consecutive women undergoing either vaginal or elective cesarean delivery under N2O general anesthesia. This suggests a transplacental inhibitory effect of N2O on methionine metabolism. Several other cases are also reported in the literature about N2O induced exacerbation of vitamin B12 deficiency syndrome resulting in neurological deterioration in adults.[16],[17]

Pneumatic compression for thromboprophylaxis and maintenance of euvolemia is must for the prevention of perioperative thromboembolic complications, whatever the choice of anesthesia may be.

Thus, the decision to use regional or general anesthesia in parturient women with hyperhomocysteinemia should be individualized and be based on a careful evaluation of risk benefit ratio.


  Conclusion Top


To conclude, this case report discusses several important anesthetic issues relevant to the management of pregnant patients with hyperhomocysteinemia, including peripartum anticoagulation and the risk of using N2O.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Mouravas H, Verettas D, Kazakos K, Xarhas K, Panagiotou N, Ellinas P, et al. Homocysteine and its relationship to deep venous thrombosis in patients undergoing total knee or hip arthroplasty. Hippokratia 2010;14:185-8.  Back to cited text no. 1
    
2.
Cerneca F, Ricci G, Simeone R, Malisano M, Alberico S, Guaschino S, et al. Coagulation and fibrinolysis changes in normal pregnancy. Increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive fibrinolysis. Eur J Obstet Gynecol Reprod Biol 1997;73:31-6.  Back to cited text no. 2
    
3.
Luzardo GE, Karlnoski RA, Williams B, Mangar D, Camporesi EM. Anesthetic management of a parturient with hyperhomocysteinemia. Anesth Analg 2008;106:1833-6.  Back to cited text no. 3
    
4.
Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999;19:217-46.  Back to cited text no. 4
    
5.
Finkelstein JD, Martin JJ. Methionine metabolism in mammals. Adaptation to methionine excess. J Biol Chem 1986;261:1582-7.  Back to cited text no. 5
    
6.
Kumar KS, Govindaiah V, Naushad SE, Devi RR, Jyothy A. Plasma homocysteine levels correlated to interactions between folate status and methylene tetrahydrofolate reductase gene mutation in women with unexplained recurrent pregnancy loss. J Obstet Gynaecol 2003;23:55-8.  Back to cited text no. 6
    
7.
Lepercq J, Conard J, Borel-Derlon A, Darmon JY, Boudignat O, Francoual C, et al. Venous thromboembolism during pregnancy: A retrospective study of enoxaparin safety in 624 pregnancies. BJOG 2001;108:1134-40.  Back to cited text no. 7
    
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James AH, Grotegut CA, Brancazio LR, Brown H. Thromboembolism in pregnancy: Recurrence and its prevention. Semin Perinatol 2007;31:167-75.  Back to cited text no. 8
    
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Eldibany MM, Caprini JA. Hyperhomocysteinemia and thrombosis: An overview. Arch Pathol Lab Med 2007;131:872-84.  Back to cited text no. 9
    
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Horlocker TT, Wedel DJ, Rowlingson JC, Enneking FK. Executive summary: Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and pain medicine evidence-based guidelines (Third edition). Reg Anesth Pain Med 2010;35:102-5. Erratum in: Reg Anesth Pain Med 2010;35:226.  Back to cited text no. 10
    
11.
Selzer RR, Rosenblatt DS, Laxova R, Hogan K. Adverse effect of nitrous oxide in a child with 5,10-methylenetetrahydrofolate reductase deficiency. N Engl J Med 2003;349:45-50.  Back to cited text no. 11
    
12.
Chambers JC, McGregor A, Jean-Marie J, Kooner JS. Acute hyperhomocysteinaemia and endothelial dysfunction. Lancet 1998;351:36-7.  Back to cited text no. 12
    
13.
Al-Obaidi MK, Stubbs PJ, Collinson P, Conroy R, Graham I, Noble MI, et al. Elevated homocysteine levels are associated with increased ischemic myocardial injury in acute coronary syndromes. J Am Coll Cardiol 2000;36:1217-22.  Back to cited text no. 13
    
14.
Badner NH, Beattie WS, Freeman D, Spence JD. Nitrous oxide-induced increased homocysteine concentrations are associated with increased postoperative myocardial ischemia in patients undergoing carotid endarterectomy. Anesth Analg 2000;91:1073-9.  Back to cited text no. 14
    
15.
Zanardo V, Caroni G, Burlina A. Higher homocysteine concentrations in women undergoing caesarean section under general anesthesia. Thromb Res 2003;112:33-6.  Back to cited text no. 15
    
16.
Hadzic A, Glab K, Sanborn KV, Thys DM. Severe neurologic deficit after nitrous oxide anesthesia. Anesthesiology 1995;83:863-6.  Back to cited text no. 16
    
17.
Lee P, Smith I, Piesowicz A, Brenton D. Spastic paraparesis after anaesthesia. Lancet 1999;353:554.  Back to cited text no. 17
    


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