Peri-operative venous thrombosis andpulmonary embolism

Peter Simpson MD, FRCA

Consultant AnaesthetistDepartment of Anaesthetics, Frenchay Hospital, Bristol, BS16 1LE, United Kingdom

Despite many signi®cant advances in surgery and anaesthesia, the incidence of deep venousthrombosis and pulmonary embolism remains unacceptably high. The occurrence and degreeof risk are related to a number of factors, involving both the patient and the surgical pro-cedure. These include the type and site of surgery, particularly if it includes the pelvis and/orlower limb and whether direct trauma or malignant disease is involved. Other patient-relatedfactors including coincidental drug therapy are discussed, together with detailed considerationof the presenting features and the methods of preventing venous thromboembolism, bothmechanically and pharmacologically. The treatment of deep venous thrombosis and pulmonaryembolism either locally or systemically is evaluated. Consideration is also given to appropriateidenti®cation of the risk to individual patients by routine accurate pre-operative assessment,allowing appropriate prophylactic measures to be instituted.

Key words: surgery; anaesthesia; venous thrombosis; pulmonary embolism; prophylaxis.

Despite major advances in surgical and anaesthetic practice, deep venous thrombosis(DVT) and pulmonary embolus (PE) remain an important cause of morbidity andmortality.1 Thromboses normally originate in the deep leg veins and many remainsymptom free, resolving spontaneously. Permanent valvular damage and chronicvenous insu�ciency may be produced, and some calf vein thromboses may pro-pagate proximally to the ilio-femoral level. These can then fragment and while somepulmonary emboli may be relatively asymptomatic others will be associated withsigni®cant clinical symptoms and may even be fatal.

INCIDENCE OF PERI-OPERATIVE DEEP VENOUS THROMBOSISAND PULMONARY EMBOLISM

At ®rst glance it would appear that little has changed over recent years to a�ect theincidence of this condition. Estimates of proximal (i.e. ilio-femoral) thrombosis rangefrom 10% in moderate-risk to 20% in high-risk patients, while the incidence of calf veinthrombosis in patients undergoing major lower-limb orthopaedic surgery is as high as80%.2 While some would argue that this high incidence is only related to the sophisti-cation of the diagnostic techniques available, it does not appear to have altered signi®-cantly in recent years except as a result of the prophylactic methods described below.

1521±6896/99/030437+13 $12.00/00 *c 1999 Harcourt Publishers Ltd.

BaillieÁ re's Clinical AnaesthesiologyVol. 13, No. 3, pp. 437±449, 1999

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Surgery itself, especially major procedures, is a signi®cant risk factor for DVT as aresult of venous stasis and tissue trauma, the risk being particularly high in lower-limborthopaedic operations and surgery for malignant disease.3,4 In one study of gynae-cological surgery the incidence of DVT was 14%, a fatal PE within the ®rst post-operative week occurring in 2.9%, and again the risk was higher in malignant disease.5

In another study of total knee replacement, the incidence of DVT was 57%, even inthose on prophylaxis, and clinically diagnosed PE occurred in 1.7% but was 7% whenventilation±perfusion (VQ) scanning was employed.6

The 1993 National Con®dential Enquiry into Perioperative Deaths (NCEPOD)report demonstrated the importance of PE as a cause of death in patients dying post-operatively, particularly in orthopaedics7, 6.5% of deaths from all types of surgerysu�ering a proven PE. Twenty per cent of deaths following hysterectomy and 42% ofdeaths following total hip replacement (THR) were attributable to PE, it being thecommonest cause of death in the latter group. In cases where the diagnosis was madeor veri®ed by post-mortem, 53% of the total hip replacement deaths and 39% of thehysterectomy deaths were due to PE.

Many randomized controlled trials of thromboprophylaxis in surgical patients havebeen carried out, mostly in general surgery (major abdominal surgery) or ortho-paedics, both elective (total hip and knee replacement) and traumatic (hip fracture).Resulting estimates of the incidence of DVT and PE rates are highest in orthopaedicsurgery. In a meta-analysis of low-dose heparin administration, 46% of electiveorthopaedic, 49% of traumatic orthopaedic and 22% of general surgery patients had aDVT identi®ed by labelled ®brinogen and 2% of all surgical patients had a non-fatal and0.8% a fatal PE.8

Recent surgical follow-up studies have suggested that the mortality from PE afterTHR may be lower than shown previously. A large follow-up study of patients under-going THR, who did not receive routine chemoprophylaxis, demonstrated a 90 day all-cause mortality of 1.1%, a total PE rate of 1.5% and fatal PE of 0.34% up to 6 monthspost-operation.9 The commonest absolute cause of death was ischaemic heart disease.These recent reductions in incidence suggest that changes in surgical and anaestheticpractice such as earlier mobilization, shorter anaesthetic and operating time and theuse of regional techniques may have reduced the risk of thromboembolic disease in hipsurgery.

The risk of thromboembolism persists after discharge from hospital, one studydemonstrating that 24.5% patients undergoing major surgery had a ®rst DVT only afterdischarge.10 Another study showed that thromboembolism was the commonest singlecause for re-admission after THR, especially in the ®rst month after discharge, when itaccounted for one-quarter of admissions (26%).11

CAUSES OF PERI-OPERATIVE DEEP VENOUS THROMBOSIS

Virchow identi®ed the pathogenesis of venous thrombosis as a triad consisting ofchanges in the vessel wall, alterations in blood ¯ow and alterations in the compositionof blood. Hypercoagulability may arise secondary to the trauma of surgery or tomalignancy, or from inherited abnormalities of the coagulation pathways, the patientsmost at risk being those with infection, metabolic disorders and malignancy.Additional factors include cardiac failure, prolonged surgery particularly in the thorax,abdomen, pelvis and lower limb, extensive trauma involving major vessels, cigarettesmoking and a past history of venous thromboembolism.

438 P. Simpson

Deep venous thrombosis formation due to changes in the vessel wall

This can result either directly from trauma or compression or indirectly from pro-longed vasodilation, as may occur during anaesthesia or immobility with autonomicdysfunction. Endothelial disruption is produced and the exposed collagen thenactivates the intrinsic coagulation pathway.

Deep venous thrombosis formation due to changes in blood ¯ow

A reduction in ¯ow and venous stasis activate coagulation and also the ®brinolyticpathway. This is caused by a number of factors, in particular prolonged surgery of thelower extremity, accompanied by reduced skeletal muscle tone and vasodilatationduring anaesthesia. Hypotension, hypothermia and hypovolaemia are all contributoryfactors, but not increased blood viscosity resulting from peri-operative dehydration.

Deep venous thrombosis formation due to changes in the compositionof blood

There are numerous factors which can a�ect the production of thrombus and whichare signi®cantly altered by surgery and anaesthesia. These include alterations in bothcoagulation and ®brinolysis, together with a decrease in the clearance of activatedclotting factors. Supplementary oestrogen therapy, commonly associated with the oralcontraceptive pill (OCP) or hormone replacement therapy (HRT), will increase theproduction of prothrombin-dependent clotting factors. Other factors include resist-ance to protein C, particularly during pregnancy, infection, malignant disease, meta-bolic disorders and coincidental drug therapy.The coagulation pathway is a balance of thrombotic and anti-thrombotic activity

mediated by coagulation proteins, of which anti-thrombin III, protein C and protein Sare responsible for anti-thrombotic e�ects. Protein C, which is activated by thrombinand thrombomodulin, inhibits coagulation by its e�ects on Va and VIlla. Resistance toactivated protein C occurs in between 20% and 60% of patients with thromboembo-lism, being produced by mutation of a gene for factor V (factor V Leiden)12 and iscommon in pregnancy and in patients taking the OCP.13 The prevalence of factorV Leiden heterozygotes in the healthy White population is 3±8%. A positive familyhistory of thromboembolism is often found particularly in younger patients who haveno predisposing factors.Several medical conditions are associated with hypercoagulability and/or immobility

and therefore predispose to venous thromboembolic disease (VTED). Malignant diseasecan release procoagulant factors, thromboembolism being a presenting feature of occultmalignancy.14,15 Stroke is associated with an increased risk of VTED as are heart failure,chronic obstructive airway disease (COAD), pneumonia and myocardial infarction.16

Although the overall incidence of VTED in pregnancy and the puerperium is low,the risk is still higher than in the non-pregnant state. Maternal mortality, however, isnow extremely uncommon.

SURGERY, ANAESTHESIA AND THE ORAL CONTRACEPTIVE PILL

It is well established that oral contraceptives increase the risk of VTED particularly inthe peri-operative period. Oestrogens increase synthesis of some vitamin K dependent

Venous thrombosis and pulmonary embolism 439

clotting factors and the `old-style' higher oestrogen and combined `pill' carried asigni®cantly increased thrombosis risk. As a result it was stopped 6 weeks pre-operatively and thrombosis prophylaxis was employed. Because ®brinogen levels wereat their lowest 4 weeks after stopping the pill, it was probably better to operate at thispoint rather than at 6 weeks, when ®brinogen was rising again.

The risk has been signi®cantly reduced by lowering the oestrogen content17,together with the introduction of the third-generation progestagens to lower cardio-vascular risk factors. There is, however, a variation in risk of VTED from combinedoral contraceptives, dependent on which third-generation progestagen is used.18

Furthermore, the risk is six times greater in those with factor V Leiden de®ciency.

SURGERY, ANAESTHESIA AND HORMONE REPLACEMENTTHERAPY

Although HRT was assumed to be only replacement therapy and not thought to beassociated with an increased risk of VTED, recent studies all indicate an increased riskin current HRT users of 2±6 times.19 The actual risk was calculated to be 16.5 cases/100 000, which is still extremely low, and all studies con®rmed the lack of residuale�ect once HRT had been stopped. Not only is the mechanism of action uncertain butalso the potential interaction with factor V Leiden and with other known risk factorsincluding recent surgery and obesity. Although HRT does increase VTED risk thismust be balanced against the other bene®ts of therapy. It should be stopped pre-operatively in medium- and high-risk patients undergoing signi®cant surgery and,although there are no ®rm recommendations, thrombosis prophylaxis should be used.

WHAT ARE THE RISK FACTORS FOR PERI-OPERATIVETHROMBOEMBOLISM IN INDIVIDUAL PATIENTS?

These can be divided into those related to the patient (e.g. age, family history ofVTED, comorbidity) and extrinsic factors related to surgery or other acute illness.Both will lead to various degrees to hypercoagulability, venous stasis and vessel walldamage. The main patient-dependent factors that in¯uence the risk of venous throm-boembolism include the older age group (440 years), obesity, malignancy, a history ofprevious DVT, varicose veins, thrombophilic states and supplementary oestrogentherapy. The risks of thromboembolism increase with age, being more common overthe age of 40 years15, 71% of deaths from PE occurring in patients over 75 years.Although rare, PE does occur at younger ages, especially when there are otherassociated risk factors. By contrast, apart from reproductive factors, a speci®c e�ect ofgender is not apparent.

The main extrinsic factors are the duration of surgery, the type of anaesthesia, pre-and post-operative immobility and the presence of sepsis. In summary, in a moderate-risk patient, over 40 years of age and undergoing a general surgical procedure longerthan 30 min, the incidence of calf vein thrombosis is 10±40%, of ilio-femoral veinthrombosis is 2±10% and of fatal PE is 0.1±0.7%. In a high-risk patient over 40 years ofage, with recent thrombophlebitis and undergoing either major abdominal or pelvicsurgery for malignancy or major lower-limb orthopaedic surgery, the incidence ofcalf vein thrombosis is 40±80%, of ilio-femoral vein thrombosis is 10±20% and of fatalPE is 1±5%.2

440 P. Simpson

The THRIFT Group have developed guidelines for assessing risk based on theevidence of the factors discussed above and they recommended that the DVT and PErisk of each patient should be assessed pre-operatively.1

A practical approach to risk assessment has been published by Autar. He con-structed a thrombosis risk factor assessment index for surgical±medical patients, basedon age, body mass index, mobility, special factors (e.g. contraceptive pill), trauma(especially lower-limb surgery), degree of surgical intervention and high-risk medicaldisease (e.g. stroke, malignancy).20 Points are awarded for each risk factor and the totalscore indicates the level of risk. This can then be linked to a prophylactic regime asshown in Table 1.

PRESENTING FEATURES AND DETECTION OF PERI-OPERATIVEDEEP VENOUS THROMBOSIS AND PULMONARY EMBOLISM

Venous thrombosis usually occurs unilaterally in the lower limb and is associated withcalf pain, swelling, discoloration and a positive Homan's sign. The diagnosis can becon®rmed in a number of ways. Ascending contrast venography is regarded as the goldstandard, but is invasive, expensive and labour intensive and runs the risk of dislodgingan existing clot. Radiolabelled (131I) ®brinogen uptake is good for detecting calf veinthrombosis but is relatively poor for iliac and pelvic vein thrombosis and has a highincidence of false positives (30% after hip surgery), because it accumulates at thewound site. Ultrasonography is easy to perform and non-invasive but is insensitiveexcept for major thrombi.Clinical manifestation of PE are also insensitive and need to be con®rmed by VQ

scan, pulmonary angiography or spiral computerized tomography. Venography willtend to overestimate the incidence of symptomatic DVT and, similarly, VQ scanningwill overestimate symptomatic PE rates.Peri-operative pulmonary embolism is classically associated with dyspnoea, chest

pain and cardiovascular collapse. If it occurs during anaesthesia, the presenting signsare tachycardia, hypoxaemia, a decrease in end-tidal carbon dioxide concentration,high in¯ation pressures, hypotension and cardiac arrhythmias. Massive pulmonaryembolism involves more than 50% of main pulmonary arteries. In addition to theseabnormal measurements, the diagnosis can be con®rmed by electrocardiogram, whichclassically shows an S1 Q3 T3 pattern, with right-axis deviation, right bundle branchblock and T wave inversion in leads V1±V4. In most cases of fatal PE there is noclinically detectable DVT and death occurs rapidly within 30 min.

Table 1. Autar risk scores.

Risk scores Points Action

None 56 NoneLow 7±10 Early mobilization, apply TED stockingsModerate 11±14 Apply TED stockings, unfractionated heparin (UFH) or low-

molecular-weight heparin (LMWH), FlotronsHigh 415 Apply TED stockings, UFH or LMWH, Flotrons

? Full anti-coagulation

TED, thrombo-embolic disease.

Venous thrombosis and pulmonary embolism 441

PREVENTION AND TREATMENT OF THROMBOEMBOLISM INGENERAL SURGERY

Physiological mechanisms

Under normal circumstances, coagulation is activated either by the intrinsic pathwayvia activated factor XII involving surface contact with damaged tissue and exposedcollagen or by the extrinsic pathway via thromboplastin. In both situations, the ®nalcommon pathway occurs via factor X, which in turn catalyses the thrombin±®brinogenreaction. Coagulation exists in dynamic equilibrium with a number of physiologicalanti-clotting mechanisms including ®brinolysis and local liberation of endogenous anti-coagulant (heparin) from mast cells. Other anti-coagulant mechanisms include clottingfactor consumption or the hepatic removal of activated clotting factors, prior toutilization.

Many of the proteins involved in the coagulation±®brinolysis pathway are released aspart of the acute in¯ammatory response. A number of physiological factors known toenhance ®brinolysis include hypercapnia, venous stasis and occlusion, menstruation,diurnal variation, catecholamines and exercise. Vasopressin also increases ®brinolyticactivity, probably by increasing the concentration of venous endothelial plasminogenactivator. In the peri-operative period, alterations occur in the concentrations of thesevarious proteins and in particular in their activated components, producing a relativeimbalance which may lead to excessive coagulation or impaired ®brinolysis. Speci®ccauses of post-operative ®brinolytic shutdown include inadequate production andrelease of plasminogen activator, accelerated clearance from the circulation, plas-minogen de®ciency and excessive inhibitors.

The ®brinolytic cascade is the de®nitive pathway for clot lysis whether resultingfrom normal or pathological thrombosis. Fibrinolysis is triggered by plasminogen,which is activated either by substances released from tissue, such as urokinase, or byblood activators, which are usually exogenous, such as streptokinase or anistreplase.Plasmin lyses ®brinogen and ®brin to their corresponding degradation products, whichthemselves possess anti-coagulant activity and which have a long half-life (412 hours).Fibrinolysis lyses additional and unwanted clot, but is itself inhibited from lysingestablished, essential clot, both by anti-plasminogen activators and by anti-plasmins.The system interacts with the coagulation cascade via activated factor XII and also withthe kallikrein±kinin and complement systems.

Pathological enhancement of ®brinolysis occurs in relation to surgery for pulmonaryand prostatic malignancy, obstetric disasters such as amniotic ¯uid embolus, placentalabruption and septic abortion, cellular blood disorders, incompatible transfusion,haemolysis, hypoxia and shock.

MECHANICAL AND PHARMACOLOGICALMECHANISMS FOR THEPREVENTION OF DEEP VENOUS THROMBOSIS ANDPULMONARY EMBOLISM

Mechanical prophylaxis

Anumberofmechanical devices are available forDVTprophylaxis. Theyaredivided intopassivemethods such as graduatedelastic compression stockings (TED) and active,whichinclude intermittent pneumatic compression (IPC) leggings, electrical calf musclestimulation and devices which produce continuous mechanical movement of feet. Ingeneral surgery, TED stockings reduce the mean incidence of DVT from 27% to 9.6%.21

442 P. Simpson

Their use prevents the dilatation of veins and formation of endothelial tears as well asincreasing the velocity of blood ¯ow.IPC leggings (e.g. Flotron) have been shown to be e�ective prophylaxis in patients

undergoing total hip replacement, reducing the incidence of DVT from 49% to 24%and of ilio-femoral vein thrombosis from 27% to 14%.22 IPC appears to be e�ective bothby preventing stasis, particularly in the soleal and femoral veins, and also as a result ofproducing intermittent venous stasis and occlusion, by activating ®brinolysis.By combining these two physical methods, the incidence of DVT was reduced from

9% in the TED group to 1% in a combined TED plus IPC group of patients undergoingmajor general surgery.23

There are hazards associated with these mechanical methods of DVT prevention.Not only can they be relatively ine�ective or inadequate, particularly if they are ill®tting, but a recent report also cautioned against the development of ischaemic ulcersin patients with occult peripheral vascular disease.24 Nevertheless, in contrast topharmacological agents, mechanical methods are not associated with haemorrhagiccomplications.

Pharmacological prophylaxis

Numerous pharmacological methods have been suggested and employed for theprevention of DVT and PE. These include low-dose UFH, LMWH, recombinanthirudin, dextran 70, anti-platelet agents (aspirin), a heparinoid analogue (Orgaron),snake venom (Ancrod), testosterone derivatives such as stanozolol (Stromba), recom-binant urokinase and warfarin. In addition, ®brinolytic activation, using either epiduralor spinal anaesthesia, has been widely used to great e�ect. A number of hazards ofpharmacological methods of DVT prevention exist, such as excessive bleeding duringsurgery, pathological bleeding, for example haemorrhagic stroke, haemarthrosis in theperi-operative period, adverse drug reactions and hypersensitivity. In addition theymay be ine�ective or inadequate and the bene®ts and risks of each must be balanced.

Low-dose unfractionated heparin

Low-dose UFH has been shown to reduce the incidence of DVT from 22% to 9% ingeneral surgery8 and is administered subcutaneously at a dose of 5000 IU at either 8 or12 hourly intervals. An international multicentre trial showed that UFH o�ered a clearadvantage in reducing the incidence of fatal PE in patients over 40 years of ageundergoing elective major general surgery. Wound haematomata occurred in a smallbut appreciable number, but clinically important bleeding did not occur.25

Low molecular-weight heparin

LMWH fractions progressively lose their ability, with reduction in molecular weight,to prolong the activated partial thromboplastin time (APTT) but retain their ability toinhibit activated factor X (Xa). The LMWH±anti-thrombin III complex is a more avidbinder of Xa than of thrombin, thereby inhibiting peri-operative activation of thecoagulation cascade but maintaining normal thrombin±®brinogen activity. Althoughthe various LMWHs share a number of common properties, they have di�erentmolecular weight distribution pro®les and rates of plasma clearance. Their speci®cactivities (anti-Xa to anti-lla activity ratio) also vary as do their recommended doseregimes. For an equivalent anti-thrombotic e�ect, LMWH produces less bleeding than

Venous thrombosis and pulmonary embolism 443

UFH in experimental models and is at least as e�ective in general surgery.26 WhileLMWH has not been shown to be more e�ective than UFH in major abdominal orcancer surgery, it is superior in major lower-limb and pelvic surgery including jointreplacement.

LMWH appears to have a number of advantages for thromboembolic prophylaxis. Ithas a high anti-thrombotic to low anti-coagulant index and a sustained anti-thromboticaction compared with UFH, necessitating only a single daily dose. It can be admin-istered via the subcutaneous route and laboratory monitoring may not be necessary inprophylaxis. LMWH has less platelet interaction than heparin, producing a lower riskof thrombocytopenia27, but the platelet count should be monitored regularly duringlong-term therapy. It is neutralized to a smaller extent by endogenous anti-heparinagents than UFH. Because of the signi®cant delayed risk of DVT and PE, particularly inmajor orthopaedic surgery, it has been suggested that LMWH should be given for upto 5 weeks after surgery. The daily cost of LWH is 5 times that of UFH.

Recombinant hirudin (desirudin)

A recent comparative study comparing hirudin with UFH in THR has shownpromising results.28 Hirudin is a potent, speci®c and almost irreversible thrombininhibitor whose e�ect is easily monitored by APTT measurement. In this study theprevalence of DVT as assessed by venography was 7% in the hirudin group and 23% inthe UFH group.

Dextran 70

Although the usefulness of dextran 70 in DVT prophylaxis is relatively small, it hasbeen shown to reduce fatal PE. In a meta-analysis of 29 studies, the incidence of fatal PEwas 0.34% in the dextran-treated and 1.5% in the control groups.29 Dextran hasinherent risks of ¯uid overload and anaphylactic reactions, although a pre-infusionhapten injection technique can reduce the latter. It also has a relatively short half-lifeand can interfere with blood cross-matching. It is thought that ®brin formed in thepresence of dextran is not cross-linked, so that it is easily lysed by the body's natural®brinolytic activity.

Anti-platelet therapy

In an overview of all randomized anti-platelet trials (predominantly of aspirin)30,therapy reduced the incidence of DVT from 27% to 19% and PE from 1.7% to 0.5%. Thedose of aspirin was in the region of 1000±1500 mg/day. Information is not available forother anti-platelet agents such as dipyrimadole (Persantin). Although other non-steroidal anti-in¯ammatory agents also a�ect platelet activity and coagulation, their usein a controlled way in the prevention of DVT is potentially overshadowed by otherproblems such as renal failure.

Oral anti-coagulants

Some surgeons use low-dose warfarin for VTED prophylaxis to good e�ect. This isinevitably in a relatively uncontrolled and unmonitored way, usually in major ortho-paedics, and is not recommended in urological surgery.

444 P. Simpson

Combination methods

Because no single method reliably abolishes DVT and PE and because heparin in excessof 5000 units increases the incidence of haemorrhagic complications, combinations ofdi�erent methods have been tried in an attempt to improve e�cacy withoutincreasing morbidity. It appears that some prophylactic methods used in combinationare more e�ective than when used singly.31 The addition of dihydroergotamine (DHE)to UFH during abdominal and pelvic surgery decreased the incidence of DVT from15% in the UFH group to 10.2% in the combined group, but DHE carries a risk ofvasospasm.In general surgical patients, the addition of pneumatic compression leggings to UFH

decreased the incidence of DVT from 22% with IPC along to 9.5% in the combinedgroup. In high-risk general surgical patients, a similar combination reduced theincidence of DVT from 16% with UFH alone to 4.4% in the combined group.32

DOES ANAESTHESIA HAVE AN EFFECT ON DEEP VENOUSTHROMBOSIS AND PULMONARY EMBOLISM?

There is no clear evidence that anaesthesia in general or individual anaesthetic agentshave any e�ect on blood coagulation or haemostasis. A number of studies have lookedat a wide variety of agents such as thiopentone, nitrous oxide, diethyl ether,cyclopropane, halothane, en¯urane, suxamethonium, D-tubocurarine, droperidol andfentanyl but have failed to demonstrate anything more than minimal disturbance to allcoagulation measurements. Hypothermia produced a mild, non-signi®cant increase inbleeding time, the signi®cance of which is uncertain.33,34

Although one study35 suggested that en¯urane produced ®brinolytic enhancement,this has not been substantiated, but, in contrast, lumber epidural and spinal anaesthesiadoes produce ®brinolytic activation.36 There is ®rm evidence that these regionalanaesthetic techniques signi®cantly reduce the incidence of DVT formation particularlyfollowing major orthopaedic surgery.37 There are a number of possible mechanisms forthis.

1. By increasing blood ¯ow in the lower limb, venous stasis is reduced and thereforethrombosis prevented.

2. Lumbar epidural anaesthesia enhances ®brinolysis so that any fresh clot which is laiddown can be rapidly lysed preventing the formation of established clot. This e�ectappears to persist if epidural analgesia is continued into the post-operative periodand there is a similar e�ect with spinal anaesthesia, but not with thoracic epidurals.

3. Bupivacaine antagonizes coagulation, although this may only be an in vitro e�ect.

SHOULD WE BE ADMINISTERING EPIDURAL ANAESTHESIA INPATIENTS RECEIVING HEPARIN PROPHYLAXIS OR FULL ANTI-COAGULATIONAS ANADDITIONALMETHODOFDEEP VENOUSTHROMBOSIS PROPHYLAXIS?

This potentially contentious question is well summarized in a recent editorial.38 Theauthors conclude that the occurrence of vertebral canal haematoma after central nerveblock is extremely rare and that the technique is safe in combination with throm-boembolism prophylaxis, provided that established guidelines are followed.39 The

Venous thrombosis and pulmonary embolism 445

recent cluster of problems following LMWH therapy in the United States is related tothe administration of signi®cantly higher and more frequent doses of heparin.

In non-obstetric patients, there does not appear to be a contraindication to the useof epidurals in patients receiving either LMWH or UFH, although many anaesthetistswould only commence heparin therapy after the block had been instituted. Similarlymany would wait until 12 hours after a heparin dose before removing the catheter. Inpatients receiving full anti-coagulation, however, regional block is normally contra-indicated.

In the obstetric patient receiving acetyl salicylic acid therapy for example, views varyand most anaesthetists would request a bleeding time ®rst. In general the bene®tsusually outweigh the risks and furthermore many would question whether blood inthe epidural space is actually a signi®cant problem, particularly in view of itswidespread use as a blood patch in the treatment of spinal headache.

TREATMENT OF THROMBOEMBOLISM IN SURGICAL PATIENTS

If a clinical diagnosis of DVT is made, it should be con®rmed by objective methodsbefore treatment commences, because long-term anti-coagulant therapy carries asigni®cant morbidity. Treatment is designed to prevent proximal propagation of thethrombus and to minimize the risk of PE. Long-term bene®ts of treatment includelimiting leg oedema and the severity of the post-thrombotic syndrome.40 While it isreasonable to observe ambulant patients with thrombi con®ned to the calf and only toinstigate treatment if they propagate to the popliteal or more proximal veins, earlytreatment is essential in immobile patients.

Anti-coagulant therapy for established venous thromboembolism normally beginswith intravenous unfractionated heparin or subcutaneous tinzaparin, overlapped andfollowed by longer-term (3±6 months) oral anti-coagulants or LMWH. The duration ofthe therapy depends on the magnitude of the thrombosis and/or the risk factorspresent.Warfarin is normally recommended for 3months for calf DVT and 3±6monthsfor proximal DVT or PE.41 The decision to commence thrombolysis in the post-operative period is a calculated one because of the increased risk of wound bleeding.

Initial treatment with UFH is usually commenced at a dose of 30 000±45 000 unitsover 24 hours for 3±5 days, depending on the individual patient's APTT. Continuousintravenous heparin is superior to subcutaneous heparin in the treatment of proximalDVT, owing to the better control of anti-coagulation achieved by the former. The aim isto achieve an APTT value within the therapeutic range (1.5±2.5 times the control)within the ®rst 24 hours and failure to achieve this is associated with a high risk (20%) ofrecurrent venous thromboembolism.41

There has been considerable recent evidence to support the replacement ofcontinuous intravenous or subcutaneous heparin by LMWH42, in both the immediateand the long-term management of VTED. Adjusted-dose LMWH is at least as e�ectiveand safe as UFH for the initial treatment of DVT. When compared with UFH, LMWHachieved better thrombolysis, produced fewer bleeding complications and lowermortality at 90 days. It also reduced the incidence of recurrent DVT and PE, whilethere was no necessity for regular monitoring.43

If warfarin sodium is used for longer-term anti-coagulant therapy, an initial dose of10±15 mg is normally given and therapy then adjusted to maintain the internationalnormalized ratio between 2.0 and 3.0.44 In patients at high risk of bleeding in theimmediate post-operative period or thosewithmultiple invasive lines, it is best to delay

446 P. Simpson

oral anti-coagulant treatment.While the e�ect of heparin can be instantly reversedwithprotamine, it may take at least 6±8 hours to reverse the e�ect of warfarin.The treatment of life-threatening PE is far more urgent and is usually largely sympto-

maticparticularly if theembolus ismassive. If possible, suspectedPEshouldbecon®rmedby a VQ scan and/or pulmonary angiography. Direct infusion of the pulmonary arterywith a thrombolytic agent such as streptokinase, together with inotropic supportive, isthe mainstay of medical treatment and pulmonary embolectomy on cardiopulmonarybypass is only performed when patients do not respond to other measures.`Umbrella' ®lters can be inserted in the inferior vena cava in patients with venous

thrombosis extending above the kneewhen anti-coagulation is contraindicated orwhenadequate anti-coagulation fails to prevent recurrent multiple small pulmonary emboli.These can be inserted either radiologically or surgically but are sometimes di�cult toplace, particularly in patients who are severely compromised from cardiorespiratorysymptoms.

HOW SHOULD WE MANAGE PATIENTS ON FULL ANTI-COAGULATION FOR ELECTIVE SURGERY?

It is essential to know the reasons for anti-coagulation and therefore whetheranticoagulants can be stopped safely. If so, warfarin should be stopped at least 48 hourspre-operatively, because of the possiblemetabolic drug interactionswhichmay develop.The patient should then bemaintained on an intravenous infusion of UFH,which can beantagonized by protamine if required. It is important to realize that subcutaneous UFHregime is insu�cient anti-coagulation for patients with metal prosthetic heart valves,although as a substitute for full anti-coagulation its use is probably su�cient in themanagement of patients in whom thrombosis would not be fatal. The safety of LMWHtherapy in this situation has yet to be established.

SUMMARY

VTED continues to be a major cause of morbidity and mortality during both electiveand emergency surgery. A number of factors have contributed to a modest reductionin its incidence such as shorter operating times and greater re®nement of surgicalinstruments and technique. Nevertheless, there remains a signi®cant group of patientswho, for various surgical and non-surgical reasons, are still at signi®cant risk ofdeveloping DVT and PE in the peri-operative period. The risk is certainly not con®nedto the operation itself, or even to the hospital stay, and it may be appropriate tocontinue therapy for several weeks in the high-risk patient. It is vitally important toidentify these patients in an e�ective and routine way as part of normal pre-operativeassessment and to institute appropriate prophylactic measures. The usefulness ofeither mechanical, pharmacological, or a combination of preventive methods must bebalanced against practicality and e�ectiveness if they are to be used routinely, togetherwith an absence of signi®cantly enhanced bleeding. Of those methods currentlyavailable, heparin, either unfractionated or low molecular weight, TED stockings andintermittent compression leggings appear the most e�ective and practical, togetherwith continuous lumbar epidural anaesthesia where appropriate. A combinedpreventive approach would seem best, involving the nursing sta� in the initial riskassessment and the surgical and anaesthetic sta� in implementing appropriate therapy.

Venous thrombosis and pulmonary embolism 447

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