PREGNANT PATIENT WITH DVT IN PAIN

24 year old second gravida with 9 weeks of pregnancy reports to the emergency department with 1 day history of pain left loin spreading to left lower limb.The patient gives history of contraceptive injections. On examination the left lower limb appeared swollen and tender. The homan's sign was positive.Femoral and Popleateal pulsations were felt but dorsalis pedis feebly felt compared to right leg. The limb was not pale or cold. A provisional diagnosis of DVT is made and a venous doppler was ordered which showed DVTof the left lower limb extending upto left ileofemoral vein.
Patient is admitted in icu, heparin infusion started 5000units iv and then 1000units/hr keeping the APTT level 1.5 to 2 times than normal.Monitoring of Spo2, ECG, NIBP and temperature commenced. Serial ABG s were performed to asses the respiratory status. Lower limb mesurements were taken frequently and observed for development of compartmental syndrome.Arterial doppler showed no arterial insufficiency and echocardiogram showed normal study. The CXR also was normal

Anesthetic referral was sent for pain relief.

Providing pain relief to this patient was a real challenge before the anaesthetist He has   to consider the following things before formulating the therapy

1) Patient is on thrombolytic therapy
2)Teratogenecity of anaesthetic agents
3)Effect of analgesic agents on uterine tone
4)Need of careful monitoring of the respiratory system as chance of pulmonary embolism is high.

NSAIDS including diclofenac sodium
Paracetamol
Paracetamol is considered to be safe and can be given intramuscular injection in case of
severe pain. But the efficacy is limited as continuous pain relief is not possible.The effects on maternal Liver like fatty liver or liver failure are of concern but are rare and occurs only on long term treatment.IV preparation is preferred as deep IM can cause hematoma formation as patient is on heparin


Diclofenac: Possible teratogenic effects reported on animal studies.Risk of miscarriage is also reported. Diclofenac must be given IM and can cause hematoma formation as patient is on heparin. Other problems of diclofenac are applicable to late pregnancy and include
Prolonged pregnancy (since NSAIDs inhibit the prostaglandins that help stimulate labor)
Increased risk of miscarriage
Possible increased risk of birth defects (although this risk appears to be small)
Poor kidney function in the fetus
Premature closure of the ductus arteriosus  in the fetus
Persistent pulmonary hypertension (a very serious lung problem) in the newborn.
(http://arthritis.emedtv.com/diclofenac/diclofenac-and-pregnancy.html)  Routine use of
diclofenac is not advised in early pregnancy

Opioids:
DO not cause congenital abnormalities or defects;(proved in animal studies)
DO not interfere with uterine contractions or the progress of labour;
Have no harmful effects on the baby's circulation except that they can reduce the normal variability in heart rate
So Tramadol, Morphine, Fentanyl etc can be given safely to mothers in early pregn ancy.Tramadol appears to be more safe as it causes less side effects like respiratory depression less nausea and vomiting and less CNS effects.The opioid effects on mother like hypoventilation, hypotension or vomiting should be considered and closely observed as these can be the manifestations of a pulm embolism!!

Epidural local analgesics:
Offers an excellent way of providing analgesia to all trimesters of pregnancy as teratogenicity and effects of drugs on uterus etc can be avoided completely.Epidural analgesia improves circulation in lower limbs, helps ambulation by providing pain relief and prevents DVT progression, but unfortunately cannot be applied here as patient is receiving heparin

Entonox: Administering 50%oxygen+50%nitrous oxide(entonox), is another way of providing pain relief.Animal studies proved the teratogenic effects of nitrous oxide as it can impair DNA synthesis by inactivation of vitamin B12. Also nitrous oxide can cause bone marrow depression and reduce uterine blood flow and hence affects fetus. But human studies do not support this and these risks may be associated with long term exposure.Hence the use of ENTONOX can be considered here.

Ketamine: The iv induction agent ketamine is found to be safe throughout pregnancy as teratogenecity is not reported.Can be used as infusion or intermittent boluses for severe pain in this case. Higher doses are found to induce uterine contractions.

THE RISK OF TERATOGENICITY IS MOST DURING THE FIRST TRIMESTER ESPECIALLY BETWEEN 3RD AND 8TH WEEKS. THIS CASE IS PRESENTED ON 9TH WEEK, SO CHANCES ARE LESS BUT CANNOT BE EXCLUDED. OPIOIDS ARE FOUND TO HAVE NEGLIGIBLE EFFECTS ON UTERINE CONTRACTION AND CAN BE CONSIDERED FOR PAIN RELIEF

DVT is not uncommon in pregnancy. The overall incidence of DVT of the lower extremities during pregnancy is 0.13 to 0.61 per thousand pregnancies. Eventhough the incidence is low DVT may lead on to pulmonary embolism, one of the common cause of maternal deaths in the developed countries. Early identifications of risk factors followed by early diagnosis and treatment helps to improve outcome for mother and infant and reduces maternal morbidity and mortality.

VTE is up to ten times more common in pregnant women than in non pregnant women of the same age and can occur at any stage of pregnancy but the puerperium is considered to be the time of highest risk. Pregnancy is considered as one of the predisposing factors for DVT as the chance of thrombosis is more due to hormonal changes, reduced venous return, venous stasis (due to compression of the IVC by gravid uterus) and immobility.The incidence of DVT is five times higher in pregnancy than in age matched non-pregnant females. The Virchow’s triad of hypercoagulability, stasis, and endothelial injury(operative intervention) exists throughout pregnancy and puerperium

Alteration in coagulation system characterised by Increased levels of clotting factors (factor I, II, VII, IX, and X) together with decreased fibrinolysis and reduced levels of the natural anticoagulant, proteinS contribute to hypercoagulability during pregnancy. Multiparity,Obesity, Operative or difficult instrumental delivery or Caesarean section, Prolonged immobility,Previous thrombo-embolism,Thrombophilias etc are the other risk factors for thrombo embolism in pregnancy.
 
Diagnosis: Non-invasive diagnostic studies such as impedance plethysmography, real time B-mode USG, and duplex doppler scanning have replaced venography as the initial screening test in the diagnosis of DVT. Venography still remains the gold standard investigating tool as it differentiates between intraluminal defects and external venous compression. The additional advantage of accurately evaluating the entire lower extremity from the calf veins to the common iliac vessels helps the clinician to plan for appropriate management.There is a risk for radiation to the fetus but estimated to be less than 0.314 rad and this can be further reduced by abdominal shielding.If the results of duplex or doppler are inconclusive, the help of venography is sought.Recently MRI has been established to be a reliable method for diagnosing pelvic and lower extremity venous thromboses and is advantageous as the risk of radiation is absent. Some blood tests which helps to establish the diagnosis are fibrinopeptide -A levels and elevated D-DIMERS.

Treatment aims

1. To prevent further extension of the thrombus.
2. To restore venous patency and thus to prevent post-phlebitic syndrome
3. To prevent pulmonary embolism or its recurrence.

In untreated DVT the risk for pulmonary embolism is estimated to be around 24% and the mortality rate is approximately 15% If patients are treated with anticoagulants, embolisation occurs in only 4.5% with a mortality rate less than 1%. So early identification and treatment are essential

Anticoagulation:

Warfarin:
Warfarin use during pregnancy is discouraged by the fact that it crosses placenta. There is 5% risk of teratogenicity if taken between 6th and 12th week of pregnancy and include nasal hypoplasia, stippled epiphyses, and limb hypoplasia. Foetal exposure at any time during pregnancy can lead to neurological abnormalities.
Heparin:

Unfractionated heparin, a naturally occurring mucopolysaccharide. It combines with antithrombin III to become a potent inhibitor of thrombin.Optimal anticoagulation is obtained with an APTT of 60-80 sec (1.5 to 2.5times control). Spontaneous haemorrhage frequently occurs if the APTT exceeds 135 sec. for periods longer than 12 hours. Before heparin is started a complete blood count, platelet count,PT, APTT, and urinalysis are obtained. The loading dose is 100U/kg with a minimum of 5,000 units. Following it, the initial infusion rate should be 15-25 units/Kg/hour. An APTT should be obtained 4 hours after the loading dose and appropriate adjustment should be made. Continuous IV infusion of heparin should be administered for 3-5 days for active thromboembolic disease or until symptoms have resolved and there is no recurrence. It is followed by adjusted dose regimen of heparin for 4-6 months followed by a prophy lactic dose for the remainder of pregnancy and 6-12 weeks postpartum.The
complications of heparin therapy are spontaneous bleeding, thrombocytopenia and
osteoporosis

Low molecular weight heparins:

These are fragments of conventional heparin produced by enzymatic or chemical breakdown.Like heparin they do not cross placenta, are nonteratogenic and are not secreted in milk.They inhibit factor Xa activity,and have minimal effect on thrombin and will not prolong APTT. Currently use of LMWHs in pregnancy is mainly confined to the chronic phase of treatment and to thrombophylaxis. Clinical trials suggest that LMWH given SC can replace the standard IV application of unfractionated heparin in the initial treatmentof DVT, granting equal or even better efficacy and potentially lower rates of adverse side effects. Full anticoagulation doses of LMWH are :ENOXAPARIN 1 mg/kg SC bd or DALTEPARIN 100 iu/kg SC bd

Thromboprophylaxis:

Advised in Acquired thrombophilia, History of DVT, PE, or other thrombotic events, Inherited thrombophilia. Regimens suggested are warfarin postpartum x 4-6 weeks or Heparin or LMWH throughout pregnancy followed by warfarin/LMWH x 4-6 wks.

Supportive care:

Leg elevation
Graduated elastic compression stocking
Mobilization with the stocking
Consider inferior venacaval filter in women with iliac vein VTE

Pulmonary embolism:
Patients present by hypotension, respiratory failure and shock.Collapsed, shocked patients need to be assessed by a team of experienced clinicians, including the oncall consultant Obstetrician, Anaesthetist and Vascular surgeon who should decide on an individual basis whether a woman receives intravenous unfractionated heparin, thrombolytic therapy or thoracotomy and surgical embolectomy.Intravenous unfractionated heparin is the preferred treatment in massive PTE with cardiovascular compromise. (loading dose of 80units/kg, 18units/kg/hour, Monitor by APTT 6 hourly).An urgent portable echocardiogram or CTPA within 1 hour of presentation should be arranged and If massive PTE is confirmed immediate thrombolysis with one of these agents, streptokinase, urokinase or recombinant tissue-type plasminogen activator, should be considered.

Ref: 1) POSTGRADUATE CLINIC; Deep Vein Thrombosis (DVT) in Pregnancy
Amita Suneja, Rashmi, Manjeet Arora, Neera Agarwal Journal, Indian Academy of Clinical Medicine, Vol. 2, No. 4 October-December 2001
2)Dr. Majida Al-Irhayim OB/GYN club ,Muscat February/2009.
3) MIllers Anaesthesia
4)Anaesthesia CME 2004,Thrissur,India
5)Hall JAG, Paut RM, Wilson KM. Maternal and fetal sequelae of anticoagulants during
pregnancy. Am J Med 1980; 68: 122-40.
6)Wong V, Cheng CH, Chan KC. Fetal and neonatal outcome of exposure to
anticoagulants during pregnancy. Am J Med Genet 1993; 145: 17-21.
7) Villasanta U. Thromboembolic disease in pregnancy. Am J Obstet Gyne 1965; 93: 142.