carbon dioxide embolism during laser endometrial ablation

CASE REPORT

Epidural blood patch for atypical headache followingobstetric epidural analgesia

S. M. Yentis and K. Haire

Magill Department of Anaesthetics, Chelsea and Westminster Hospital, Fulham Road, London SW10 9NH, UK

SummaryA case of atypical headache presenting following otherwise unremarkable epidural analgesia inlabour is presented. Although there was no suggestion of accidental dural puncture duringinsertion of the epidural catheter, and despite the unusual features of the headache andcomplicated case history, an epidural blood patch was performed 13 weeks post-partum, withimprovement of the patient’s symptoms. A repeat epidural blood patch 2 weeks later completelyresolved her headache.

Keywords Anaesthetic techniques, regional; spinal, blood patch. Complications; headache.

......................................................................................Correspondence to: Dr S. M. YentisAccepted: 21 August 1996

It has been suggested that the incidence of accidental duralpuncture in obstetric practice should be less than 1% inteaching centres [1]. It is known that patients may experi-ence post-dural puncture headache (PDPH) followingotherwise unremarkable epidural analgesia and it has beensuggested that the Tuohy needle may damage the duraduring insertion, with rupture of the dural tear laterresulting in PDPH [2]. Typical features of PDPH includefrontal and/or occipital headache aggravated by theupright position and relieved by lying; nausea and vomit-ing; auditory and visual symptoms; and neck stiffness [3].Whilst epidural blood patch is an effective treatment forPDPH [1], anaesthetists may be reluctant to perform ablood patch when the headache and associated symptomsare atypical, since the headache may have a differentaetiology and the technique is not without complications[1]. We report a case in which there was considerabledoubt on the part of the medical staff as to the aetiology ofheadache and associated symptoms, but in which twoblood patches were eventually successful.

Case history

A previously healthy 33-year-old woman was referred tothe anaesthetic department complaining of severe head-aches following delivery of a healthy female baby at term.

Her pregnancy (her first) had been complicated bymigraneous headaches beginning in the first trimesterconsisting of unilateral retro-orbital pain associated withphotophobia, nausea and vomiting. They often lastedseveral hours and were initially responsive to daily aspirin75 mg. However, the headaches recurred in the thirdtrimester and she was admitted to hospital at 37 weekswith severe right-sided headache and a blood pressure of180/105 mmHg. Her headache and blood pressure settledover 48 h but in the following 2 weeks she experiencedintermittent headaches and fluctuating blood pressurewith diastolic 95–100 mmHg. Her urine, previouslyclear, became strongly positive for protein; she becameodematous in her limbs and her serum urate was raised.Labour was induced at 39 weeks and she requestedepidural analgesia at 2 cm cervical dilatation.

A 16 G epidural catheter was inserted at the L2/L3interspace without difficulty by an experienced anaestheticregistrar through a 16 G Tuohy needle with the bevelpointing cranially, using loss of resistance to saline. Shereceived the standard epidural regimen in use at ourhospital, consisting of 15 ml 0.1% plain bupivacaine with30 mg fentanyl as the initial dose and 10-ml boluses of0.1% bupivacaine with 2.0 mg.mlÿ1 fentanyl as required.She received a total of 19 boluses during her 18-hlabour, with three additional boluses of 10 ml 0.25%

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plain bupivacaine towards the end of labour when the low-dose regimen became inadequate. AVentouse delivery wasfacilitated by 5 ml epidural 2% lignocaine. She did notsuffer with headache during labour and her diastolicpressure remained between 85 and 95 mmHg.

Her headache returned 3 days later, now more throb-bing in nature than previously and right occipitofrontalwith no associated symptoms. She was seen by a consultantanaesthetist who felt PDPH was very unlikely and wasdischarged 2 days later with no headache. She was startedon nifedipine by her general practitioner for raised bloodpressure 3 days later; her headache worsened and she wasagain seen by an anaesthetist who felt PDPH was unlikely.Her nifedipine was stopped and atenolol substituted andshe was referred for neurological assessment and compu-terised tomography (CT) scan, both of which werenormal. Neurological opinion was a diagnosis of migraine,whilst a separate consultation at a migraine clinic resultedin a diagnosis of tension headache.

Her next presentation to the anaesthetic departmentwas at 11 weeks post-partum complaining of occipitalheadache associated with mild neck stiffness, tinnitus,nausea and photophobia. The headaches were presentwhen she woke in the morning and did not alter whenshe stood up, although she reported that they were some-times relieved when she lay down during the day. Theywere severe and prevented her from performing hernormal activities. She referred many times to two anaes-thetic textbooks relating to epidural anaesthesia that shehad brought with her, each with several passages ofrelevant text highlighted. She also admitted to a previoushistory of eating disorders and was receiving counsellingfrom a psychotherapist, but felt that her symptoms wereunrelated to her psychological state, a view which wasapparently shared by her psychotherapist. Neurologicalexamination relieved no abnormality. Firm pressure overthe right hypochondrium eased her headache slightly.

The possible aetiology of her headaches, including thepossibility of unrecognised dural puncture either at thetime of insertion of epidural catheter or subsequently, wasdiscussed. The risks and possible benefits of epidural bloodpatch were discussed at great length, and it was decided toproceed with a blood patch, partly to reassure her that allpossible forms of treatment were being pursued, althoughshe accepted that it might not succeed.

During the interview, the patient appeared quite rationaland earnest and was very sensitive to the possibility shemight be labelled as a difficult and demanding patient.Indeed, this aspect was also discussed at length but hersymptoms were felt to be real and incapacitating.

An epidural blood patch was performed in the left lateralposition at L3/L4 using 20 ml fresh autologous bloodthrough a 16 G Tuohy needly under aseptic conditions.

After lying supine for 2 h, her headache had improvedslightly, with a verbal rating score (VRS) of 6/10 beforethe blood patch and 4/10 after it. Her tinnitus was stillpresent, although her neck stiffness had eased slightly. Twoweeks later her symptoms were unchanged. One weekafter the blood patch she did experience a migraine lasting48 h, superimposed on the underlying headache and quitedifferent in character from it. After further lengthy discus-sions, it was agreed that one final blood patch would beperformed and this was done the same week, using 14 mlof fresh blood injected at L2/3. Two hours later hersymptoms had completely resolved with a VRS of zero.She has suffered occasional mild migraine-like headachessince, but has been able to lead a normal life. Her lastcontact with the anaesthetic department was 2 monthsafter her final blood patch, and she was seen once more bythe neurologists 2½ months after this when she wasdischarged from their clinic on no medication.

Discussion

When PDPH follows a recognised dural puncture and itsfeatures are classic, it usually presents little difficulty inmanagement other than whether or when to perform anepidural blood patch. This decision depends on theseverity of the symptoms, their duration and the wishesof the patient, bearing in mind that there are rare butserious consequences of an untreated PDPH [1] and thatblood patching has a 91–100% success rate [4] but mayitself have undesirable effects including back pain, neckpain, nerve root irritation and fever [5]. In our patient,however, there were a number of different factors that mayhave contributed to her headache and it was difficult to becertain of the exact cause. Migraine and pre-eclampsia areboth associated with the symptoms that she described andit was difficult not to be influenced by her previouspsychological problems, although she was at pains tostress that these were under control and she had beenliving a normal life up until her pregnancy. Indeed, wefound that her behavior and reactions were no more thanwe would have expected from anyone who felt that hersevere and distressing symptoms were not being takenseriously. Before being referred to the anaesthetic depart-ment, she had consulted with a number of health careworkers including general practitioner, midwives, neuro-logists, obstetricians, acupuncturist and homeopathic prac-titioner and felt (rightly or wrongly) that she had not beenheard sympathetically by any of them.

It is possible that our patient’s dura was indeed acciden-tally punctured during the siting of her epidural catheter.Free flow of cerebral spinal fluid (CSF) does not alwaysaccompany dural puncture, even with a 16G Tuohy needle[6], although there were no features of the subsequent

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block that would have suggested subarachnoid placementof the catheter or local anaesthetic. It is possible that manydural taps go unreported, perhaps because the traineeconcerned is anxious about subsequent repercussions. Inthis case, the registrar was questioned about the case andclaimed no hesitation in owning up had he felt that a duraltap had occurred. A final possibility is that a dural tear wasmade without initial leakage of cerebrospinal fluid (CSF)[2]; this has been claimed to be more likely when theneedle is inserted with the bevel parallel to the dural fibresand then rotated [7], although this was not done in ourpatient. The incidence of typical PDPH following other-wise apparently unremarkable epidural analgesia in obste-trics is uncertain, although Okell & Sprigge reported sevenpatients out of 3500 women receiving uncomplicatedobstetric epidural analgesia who developed typical PDPH,two of whom subsequently required blood patching [2].Ravindram et al. reported five cases of low-pressure head-ache out of 352 women receiving epidural analgesia forlabour, four of whom required blood patching [8]. Thesehigh incidences do not reflect our own experience, northat of colleagues with whom we have consulted fromother units; for example, out of the last 2000 womenreceiving obstetric epidural analgesia in our unit sinceusing a computerised audit system with detailed post-partum follow-up, this has been the only case of severeunexplained headache and the only time blood patchinghas been performed without a history of definite duralpuncture. It is possible that in these two series [2, 8], otherfactors were involved such as inexperience of the operator,differences in equipment used (for example 12 G needlesused in the study by Ravindran et al. [8]) or otherdifferences in practice relating to that time.

The mechanism by which an epidural blood patchworks is not fully understood. The theory that the bloodplugs a hole in the dura is supported by demonstration ofthe blood adhering to the puncture site using advancedimaging techniques [9]. However, it is possible that othereffects relating to pressure changes in epidural and sub-arachnoid compartments may be involved [10]. Thus, forexample, blood patching has been successfully used at thelumbar level to treat PDPH following accidental dural tapat the cervical level [11]. In addition, Parris reported theuse of blood patching to treat patients with chronic head-ache not associated with deliberate or accidental duralpuncture or indeed with regional anaesthesia of any kind[12]. It is possible that our patient’s symptoms wereunrelated to epidural anaesthesia and/or unrecogniseddural puncture. Her response to blood patching maytherefore have been nonspecific rather than related speci-fically to PDPH.

This case was a difficult one to manage, in view of theuncertain aetiology of her symptoms and the frustrationthat was obviously felt by herself and perhaps by some ofthe doctors and midwives that she had encountered. Weourselves learnt some important lessons from the case, notleast the importance of not allowing labels such as ‘difficultpatient’ or those relating to possible psychological factorsto influence our management in a negative manner. Inaddition, we suggest that anaesthetists should be moreready to consider an epidural blood patch even if patients’symptoms do not fit the classic picture of PDPH, oncemore serious intracranial pathology has been ruled out.

Acknowledgment

We are grateful to Simone Bird for secretarial assistance.

References

1 Reynolds F. Dural puncture and headache. British MedicalJournal 1993; 306: 874–6.

2 Okell RW, Sprigge JS. Unintentional dural puncture. Asurvey of recognition and management. Anaesthesia 1987; 42:1110–3.

3 Lybecker H, Dyernes M, Schmidt JF. Postdural punctureheadache (PDPH): onset, duration, severity and associatedsymptoms. Acta Anaesthesiologica Scandinavica 1995; 39: 605–12.

4 Shnider SM, Levinson G. Anesthesia for cesarean section. In:Shnider SM, Levinson G, eds. Anesthesia for Obstetrics, 3rdedn. Baltimore: Williams and Wilkins, 1993: 211–45.

5 Weeks SK, Postpartum headache. In: Chestnut DH, ed.Obstetric Anaesthesia. St Louis: Mosby, 1994; 606–20.

6 Holloway TE, Telford RJ. Observations on deliberate duralpuncture with a Tuohy needle: depth measurements.Anaesthesia 1991; 46: 722–4.

7 Meiklejohn BJ. The effect of rotation of an epidural needle.Anaesthesia 1987; 42: 1180–2.

8 Ravindran RS, Albrecht WH, Tasch M. Low pressureheadache following successful continuous lumbar epiduralanalgesia. Anesthesia & Analgesia 1980; 59: 799–800.

9 Beards SC, Jackson A, Griffiths AG, Horsman EL. Magneticresonance imaging of epidural blood patches: appearancesfrom 30 min to 18 h. British Journal of Anaesthesia 1993; 71:182–8.

10 Carre LE. Epidural blood patch: why the rapid response?Anesthesia & Analgesia 1991; 72: 129–30.

11 Colonna-Romano P, Linton P. Cervical dural puncture andlumbar extradural blood patch. Canadian Journal of Anaesthesia1995; 42: 1143–4.

12 Parris WCV. Use of epidural blood patches in treatingchronic headache: report of six cases. Canadian Journal ofAnaesthesia 1987; 34: 403–6.

Case reports Anaesthesia, 1997, 52, pages 62–76................................................................................................................................................................................................................................................


CASE REPORT

Carbon dioxide embolism during laser endometrialablation

M. Kelly,1 H. M. L. Mathews2 and P. Weir3

1 Department of Anaesthetics, Royal Victoria Hospital, Grosvenor Road, Belfast BT12 6AB, UK2 Department of Anaesthetics, and 3 Department of Obstetrics and Gynaecology, Mater Hospital Trust, Crumlin Road,Belfast BT14 6AB, UK

SummaryA patient undergoing endometrial ablation with an Nd-YAG laser, a carbon-dioxide-cooledcoaxial fibre and an exposed fibre tip suffered a carbon dioxide embolism resulting in cardiacarrest. A full recovery was made with no neurological deficit.

Keywords Embolism; carbon dioxide. Complications; arrest, cardiac. Surgery; laser, gynaecological.

......................................................................................Correspondence to: Dr H. M. L. MathewsAccepted: 16 September 1996

Endometrial ablation with an Nd-YAG laser as an alter-native to hysterectomy to control abnormal uterine bleed-ing was first described in 1981 [1]. This was a newtechnique being introduced into our hospital for the firsttime and two patients were scheduled for this procedureon the same operating list. Both procedures were carriedout by a fully trained consultant with extensive experiencein the use of, and familiar with, the Nd-YAG laser, assistedby a consultant in training. The first operation had passeduneventfully and we describe the complications occurringwith the second patient.

Case history

The patient was a 47-year-old woman, with a 2-yearhistory of menorrhagia, resulting in iron deficiency anae-mia. Apart from essential hypertension, which was wellcontrolled with nifedipine 30 mg daily, she had no sig-nificant cardiac or other past medical history and was anonsmoker. On pre-operative anaesthetic assessment therewere no abnormal physical findings and routine biochemi-cal and haematological screening showed no abnormality.A 12-lead ECG carried out on the day prior to operationwas within normal limits with no evidence of left ven-tricular hypertrophy. Temazepam 20 mg orally 1 h pre-operatively was prescribed as premedication and nifedipinewas continued in the pre-operative period. Routinemonitoring of ECG, noninvasive blood pressure (NIBP),

capnography and pulse oximetry was commenced atinduction of anaesthesia and continued throughout theprocedure. Since this was a new procedure in the hospitaland the duration of operation was uncertain it was decidedthat tracheal intubation and pulmonary ventilation wasindicated.

Following pre-oxygenation, anaesthesia was inducedusing propofol 2.5 mg.kgÿ1 and fentanyl 0.1 mg and thetrachea was intubated following atracurium 35 mg. Anaes-thesia was maintained with isoflurane 1–1.5%, nitrousoxide 60% and oxygen 40% with intermittent positivepressure ventilation to achieve normocapnia. The patientwas placed in the dorsal lithotomy position. Endometrialablation was started using an Nd-YAG laser fibre, consist-ing of a coaxial sheath and an exposed tip, i.e. in contactmode, via an 8-mm Olympus operating hysteroscope. Thedistension medium was 0.9% saline. The laser fibre was acoaxial noncontact fibre adapted to be used in the directcontact mode. The Nd-YAG laser requires the use ofcarbon dioxide (CO2) gas flowing between the outersheath and the inner fibre as a coolant. The machine hada safety interlock which would prevent its operation if thegas was not flowing.

Approximately 20 min after the start of endometrialablation the patient suddenly developed a tachycardia;immediately after this the waveform of the pulse oximeterbecame flattened but still showed an O2 saturation of 98%.The position of the probe was checked and the radial and



carotid pulses palpated and found to be absent; the patientthen developed a heart rate of 30 beat.minÿ1, unrespon-sive to atropine 0.6 mg and this proceeded to asystole. Adiagnosis of cardiac arrest was made and cardiopulmonaryresuscitation commenced; nitrous oxide and isofluranewere discontinued and surgery stopped. External cardiacmassage and ventilation with 100% O2 were continued for1½–2 min and adrenaline 1 : 10 000 3 ml was given intra-venously. The gynaecologist commented that there hadbeen a lot of gas bubbles in the uterine cavity prior to thecollapse of the patient. On auscultation over the precor-dium at this stage a loud mill-wheel murmur was heard,which quickly disappeared. Cardiac output returned, witha heart rate of 120 beat.minÿ1 with marked ST elevationand NIBP recorded at 200/110 mmHg.

A radial arterial line and a right internal jugular centralvenous line were inserted, but no air or foamy blood wasaspirated from the central line, presumably because thepatient’s cardiac output had recovered at this time. Arterialblood gas analysis showed a pH of 7.4, PaCO2 of 4.8 kPaand a PaO2 of 73.6 kPa (F IO2 1.0). During the 10 minperiod after cardiovascular collapse the patient requiredtwo boluses of adrenaline 1 : 10 000 0.5 ml to maintain herblood pressure, but thereafter the cardiovascular systemremained stable. Fentanyl 0.1 mg and increments of mid-azolam were administered to prevent awareness.

On examination the patient’s right pupil was noted tobe dilated and unreactive whilst the left pupil was smallerand reacting sluggishly, suggesting the possibility of cere-bral gas embolism. Mannitol 20% 50 ml and dexametha-sone 8 mg were given. Following stabilisation she wastransferred to the intensive care unit (ICU) and on arrivalshe was moving all limbs and responding to commands in apurposeful way. It was therefore decided to remove thetracheal tube, after which she was awake and orientatedwith no recall of intra-operative events. She subsequentlyconfirmed that one pupil had always been larger than theother. A chest X-ray was normal and ECG showed no newchanges. She remained in ICU overnight but was dis-charged to the ward the following day. She had anuneventful hysterectomy some months later although shedeveloped a pulmonary embolus postoperatively despiteperi-operative prophylaxis with subcutaneous heparin.

Discussion

Carbon dioxide embolism has been described duringlaparoscopy, laparoscopic choleycystectomy and hystero-scopy [2]. Crozier et al. [3] reported three cases of carbondioxide embolism during hysteroscopy. Three fit healthyyoung women developed signs of embolism 5–8 min afterthe beginning of insufflation of gas. There was an initial

tachycardia followed by a ventricular arrhythmia, brady-cardia and cardiac arrest. A decrease in end-tidal CO2 wasnoted during the tachycardia. All patients were successfullyresuscitated with cardiopulmonary resuscitation and adre-naline and a ‘millwheel’ murmur was present in each case.

This case report follows a similar pattern. Although theend-tidal CO2 was being measured, during the process ofresuscitation it was not observed and although the PaCO2

was normal on the arterial sample, this was taken sometime after the event. The successful outcome was due tothe rapid detection of the embolism, removal of the sourceof the gas and the high solubility of carbon dioxide inblood. Spontaneous recovery occurred before aspirationof intravascular gas from the right internal jugular wasattempted.

Sheathed fibres terminating in an artificial sapphire tipare used in conjunction with Nd-YAG lasers. Contactsurgery with sapphire tips is accomplished by laser-induced heating of the sapphire protein. Substantial heat-ing of the sapphire tip can burn the laser fibre tip. Air,nitrogen and carbon dioxide have all been used as coolingmedia and are transmitted via an outer coaxial sheath tothe tip. A liquid environment provides adequate cooling ofthe laser fibre and CO2 in the coaxial sheath is unnecessary.Deaths caused by gas embolism using this system have beenreported by Baggish & Daniell in 1989 [4]. They con-cluded that no gas of any sort should be used to cool laserfibre tips when operating in a fluid medium, as in intra-uterine surgery. In this case saline was used to distend theuterine cavity and since the tip was in a liquid environmentit was unnecessary to cool the fibre with CO2.

Since the Nd-YAG laser was being commissioned, thesupplier’s representative was present during the first endo-metrial ablation and he had previously stripped back theouter coaxial sheath containing the CO2. During thesecond case, a new laser fibre was used which inadvertentlyhad an intact outer sheath extending close to the laser tipand into the hysteroscope, conducting CO2 into the uterinecavity and resulting in the near catastrophic CO2 embolism.

We wish to highlight the dangers of operating in theuterine cavity with coaxial laser fibres cooled by CO2. Ifthe laser system requires CO2 to be administered down thecoaxial sheath to allow it to function, the outer sheathmust be adequately stripped back to ensure that it does notenter the hysteroscope and that no CO2 enters the uterinecavity. Anaesthetists should be particularly vigilant whennew techniques are introduced into a hospital and shouldbe aware that gas or CO2 embolism can occur during lasersurgery.

Acknowledgment

Mr E. Kearney, Medical Technical Officer.



References

1 Goldrath MH, Fuller T, Segal S. Laser photovaporization ofendometrium for the treatment of menorrhagia. AmericanJournal of Obstetrics and Gynecology 1981; 140: 14–9.

2 Brink DM, De Jong P, Fawcus S, Marot N. Carbon dioxideembolism following diagnostic hysteroscopy. British Journal ofObstetrics and Gynaecology 1994; 101: 717–8.

3 Crozier TA, Luger A, Dravecz M, et al. Gas embolism withcardiac arrest during hysteroscopy. A case report on 3patients. Anesthesiologie 1991; 26: 412–5.

4 Baggish MS, Daniell JF. Catastrophic injury secondary to theuse of co-axial gas-cooled fibers and artificial sapphire tipsfor intrauterine surgery: a report of five cases. Lasers inSurgery and Medicine 1989; 9: 581–4.

CASE REPORT

Anaesthetic management of childhood thyrotoxicosis andthe use of esmolol

J. D. Knighton and M. M. Crosse

Shackleton Department of Anaesthesia, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK

SummaryWe report a case of infantile thyrotoxicosis requiring thyroidectomy while biochemicallyhyperthyroid, detailing the use of esmolol to control a thyrotoxic episode.

Keywords Complications; thyrotoxicosis. Surgery; thyroidectomy. Sympathetic nervous system;pharmacology, esmolol.

......................................................................................Correspondence to: Dr M. M. CrosseAccepted: 6 September 1996

Thyrotoxicosis in neonates and infants is a rare condition,almost always caused by autoimmune hyperthyroidism [1]and usually related to maternal transmission of thyroidstimulating antibodies. It is usually adequately treated withantithyroid medication in the same manner as in adults [2].Neonatal thyrotoxicosis caused by genetic mutation hasbeen documented, in which hyperthyroidism was difficultto control and the patient required subtotal thyroidectomyfollowed by radio-iodine treatment [3].

We present a rare case of nonautoimmune hyperthy-roidism in a young child which was resistant to medicaltherapy and required total thyroidectomy. We discuss thepreparation and anaesthetic management of this child,including the use of esmolol to control a thyrotoxiccrisis and review the anaesthetic management of patientswith uncontrolled hyperthyroidism.

Case history

The patient presented at the age of 4 months withdevelopmental delay, failure to thrive and repeated bouts

of diarrhoea. On examination, she was malnourishedwith weight well below the fifth percentile for age, had atachycardia of 160 beat.minÿ1 and had marked exo-phthalmos. Her thyroid function tests revealed a TSH<0.01 mU.lÿ1 and free T4 >100 pmol.lÿ1 (normal range9–24). Thyroid stimulating antibodies (thyroglobulin anti-bodies and thyroid microsomal antibodies) were undetect-able. She was treated with propranolol by mouth inincreasing doses until symptomatic control was achieved,but carbimazole failed to render her biochemically euthy-roid. In view of the large dose of propranolol (19 mg, 8hourly) and the failure of carbimazole, the child wasreferred for total thyroidectomy at the age of 14months.

On admission for surgery the patient was still receivingpropranolol 19 mg three times daily and, in addition,Lugol’s iodine 0.3 ml three times daily had been prescribedfor 3 weeks before the planned surgery. Despite thistreatment the heart rate was only controlled to130 beat.minÿ1 and the patient remained hyperthyroidwith free T4 of 34.7 pmol.lÿ1 [6].



At pre-operative anaesthetic assessment the childweighted 7.2 kg (5th percentile for age) and had a heartrate of 120 beat.minÿ1, but there were no signs of cardiacfailure. Inspection of the neck revealed no goitre, notracheal deviation or evidence of airway obstruction andno difficulties with tracheal intubation were anticipated.Routine pre-operative investigations were normal as werechest radiography and echocardiogram.

The patient was premedicated with temazepam 2.5 mgby mouth and accompanied to the anaesthetic room byher mother. Inhalation induction of anaesthesia was per-formed with nitrous oxide, oxygen and isoflurane usingnoninvasive monitoring (pulse oximetry and ECG), ablood pressure cuff being applied once consciousness waslost. The airway was easily maintained while a 22G intra-venous cannula was sited in a forearm vein, a 24G peri-pheral arterial line inserted into the radial artery and adouble lumen central venous cannula inserted through thefemoral vein. Having established full invasive monitoringof arterial blood pressure and central venous pressure(CVP), fentanyl 3 mg.kgÿ1 and vecuronium 0.1 mg.kgÿ1

were administered intravenously and the trachea intubatedwith a 4.0-mm uncuffed tracheal tube. Additional moni-toring included oesophageal stethoscope, capnographyand rectal temperature. Anaesthesia was maintained bypositive pressure ventilation using nitrous oxide, oxygenand isoflurane with increments of vecuronium and fen-tanyl as required.

The surgery, which lasted 3 h, proceeded uneventfullywith no cardiovascular response to laryngoscopy or mani-pulation of the thyroid gland and only minor changes inarterial blood pressure and heart rate (within 20% ofbaseline values). After reversal of neuromuscular blockadethe trachea was extubated and the patient transferred to therecovery area where oxygen was given by face mask and allintra-operative monitoring was continued. There was noevidence of airway obstruction and heart rate rangedbetween 120–140 beat.minÿ1 with arterial blood pressurestable at around 85/60 mmHg.

Three hours after transfer from the operating theatre thepatient became sweaty, agitated, pyrexial (38 8C) andtachycardic (185 beat.minÿ1) despite good analgesia, sug-gesting the onset of a thyrotoxic state. Intravenous bolusdoses of esmolol were given in 1-mg increments, to atotal of 8 mg, until the heart rate was controlled to below160 beat.minÿ1, after which an intravenous infusion wasstarted at 75 mg.kgÿ1.minÿ1. Once the heart rate wascontrolled to below 150 beat.minÿ1 and the temperatureand arterial blood pressure returned to baseline values, therate of esmolol infusion was reduced to 60 mg.kgÿ1.minÿ1.

Propranolol was restarted by mouth 6 h after the endof the procedure and the infusion rate of esmololwas gradually reduced until stopped after 12 h. Invasive

monitoring was continued for a total of 36 h postopera-tively during which there were no adverse events. Pro-pranolol medication was gradually reduced and thenstopped on the fifth postoperative day. The child wasthen started on thyroxine replacement therapy.

Discussion

Thyrotoxicosis is rare in the first year of life, with asuggested incidence of around 1 in 1000 000 [4]. It isusually the result of autoimmune hyperthyroidism (Graves’disease) [1] but this rarely requires surgical intervention toachieve control [5]. A few cases of congenital nonautoim-mune hyperthyroidism have been described in whichthere were persistently negative thyroid autoantibodies.In these cases, although the clinical manifestations werepartially controlled by b adrenoceptor blockade, subtotalor total thyroidectomy was necessary to fully correct thehyperthyroid state [3]. Similarly, occasional cases of auto-immune hyperthyroidism fail to respond to drug treat-ment, necessitating thyroidectomy in the hyperthyroidstate and posing considerable problems for the anaesthetist.

Peri-operative risks include thyrotoxic crisis, airwaycompromise, arrhythmia, cardiac failure, laryngeal nervedamage and hypoparathyroidism. If total thyroidectomy isperformed, thyroxine replacement should be commencedbefore clinical hypothyroidism becomes manifest.

Like adults, children presenting for thyroidectomyshould be clinically and biochemically euthyroid beforeoperation to decrease the risk of thyroid storm. Pre-operative preparation usually includes the use of antithy-roid drugs such as carbimazole or propylthiouracil withiodide solutions to inhibit iodothyronine synthesis andthyroxine release, the effective dose of the latter being ofthe order of 2–4 mg.kgÿ1.dayÿ1 [6].

In thyrotoxicosis, increased adrenergic activity is notassociated with elevated plasma catecholamine concen-trations but thyroid hormones may sensitise adrenergicreceptors to endogenous catecholamines [7]. Persistentlyelevated thyroid hormone concentrations may result in b

adrenoceptor upregulation [8]. Thyrotoxic symptoms arecontrolled by adequate b adrenoceptor blockade, usuallywith propranolol by mouth starting at doses of2 mg.kgÿ1.dayÿ1 and increasing as necessary. Muchlarger doses may be required because of the increasedclearance of propranolol in thyrotoxicosis [9, 10]. Dosageis usually adjusted according to resting heart rate, althoughthis may not always give a reliable indication of the degreeof b blockade in hyperthyroidism [11]. The use of b

blockade alone has been suggested as adequate preparationfor surgery in thyrotoxicosis [12].

Patients must be assessed for evidence of heart failure,cardiomyopathy or arrhythmias. In adults and possibly also



children, there may be tachypnoea, decreased vital capa-city and lung compliance and altered ventilatory responsesto hypoxia and hypercapnoea [13]. If there is thyroid-related eye disease the cornea must be protected. Theremay be difficulty with tracheal intubation owing totracheal compression or deviation and, in congenitalnonautoimmune hyperthyroidism, associated anatomicalabnormalities of the upper airway have been described[3].

Benzodiazepine premedication is safe and may reducethe excess catecholamine output associated with pre-operative anxiety, which may in itself increase the risk ofa thyrotoxic crisis [14]. Larger doses may be required if themetabolic rate remains elevated. We chose a dose that wehoped would provide adequate pre-operative anxiolysiswithout excessive sedation, in case of unexpected airwaycompromise. The presence of a parent in the anaestheticroom was also intended to minimise distress to the childand so limit catecholamine release. Anticholinergic drugsshould be avoided because of their effects on temperatureregulation and heart rate. Isoflurane was used in preferenceto other volatile agents because of its relative cardiovascularstability and predictability and to avoid possible concernswith liver metabolism and hepatitis [15].

Thyrotoxic storm, or crisis, is a rare but life-threateningcomplication associated with inadequate thyroid blockadeat a time of excessive thyroid hormone effect [14]. Thegreatest risk is likely to be at times of cardiovascularstress, during laryngoscopy and tracheal intubation,manipulation of the thyroid gland [16], or in the 6–18 h postoperative period [17]. For this reason inha-lation induction of anaesthesia with noninvasive moni-toring was followed by the setting up of invasivemonitoring devices before there was any instrumenta-tion of the patient’s airway. Accurate monitors were thenavailable to measure and record data before any likelystimulus was applied.

The onset of a thyroid crisis is characterised by ahyperdynamic circulation with tachycardia, hyperthermiaand hypertension suggesting excessive sympathetic ner-vous system activity. This may progress to cardiovascularcollapse, profound metabolic acidosis and death. Invasivemonitoring of arterial blood pressure and central venouspressure is advantageous, particularly in young childrenwhose cardiac output may readily be affected by hypo-volaemia or altered heart rate. The prompt recognitionand treatment of thyrotoxic storm is likely to increase thechances of a favourable outcome. Continuous monitoringof temperature is mandatory as progressive fever is acardinal sign of thyrotoxic crisis.

In cases where there is a risk of peri-operative thyro-toxic crisis, treatment must be readily available. In additionto cooled intravenous fluids and cooling blankets, a range

of directly acting vasodilators and vasopressors should beprepared in appropriate doses. The mainstay of immediatetreatment, however, is the re-establishing of adequate b

adrenoceptor blockade [18]. Propranolol intravenously iscommonly used, but its relatively slow onset and longduration of action are less than ideal in a rapidly changingclinical crisis. The case presented illustrates that the b1

selective antagonist, esmolol, may be of use in children, asin adults [19]. Its rapid onset and short elimination half-lifemake it suitable both for use as an incremental bolusinjection and by infusion [20]. Bolus doses of 0.25–0.5 mg.kgÿ1 have been recommended in infants, titratedagainst effect, followed by maintenance infusion rates of50–100 mg.kgÿ1.minÿ1 [21]. There is little informationon the pharmacokinetics of esmolol in children or inthyrotoxic patients and, as far as we are aware, its use ininfantile thyrotoxicosis has not previously been reported.Published work in adults suggests that higher infusionrates may be required in thyrotoxicosis [19], although inthe child presented there was a response well within theestablished adult dose range.

After tracheal extubation, these patients should bemonitored in a well-equipped paediatric recovery areafor signs of airway compromise, thyrotoxic crisis or hae-morrhage. Fluid balance may be difficult to assess in ahypermetabolic patient with large insensible losses andmay be facilitated by the use of central venous pressuremonitoring. Once stable, patients will usually be trans-ferred to a high-dependency area for continuing obser-vation. Esmolol allows accurate titration of dose againstresponse in the postoperative period when oral medicationmay be inappropriate.

After operation there is a possibility of hypocalcaemiasecondary to hypoparathyroidism if the parathyroids havenot been preserved; this may present either early within1–3 h, or late, after 24–72 h. There may be the classicalsigns of hypocalcaemia, or inspiratory stridor progressingto laryngospasm owing to the sensitivity of the laryngealmuscles to hypocalcaemia [17]. Intravenous calcium maybe required in some cases.

Total thyroidectomy is an operation rarely performed invery young children. It may be required for uncontrolledthyrotoxicosis in rare cases such as congenital nonauto-immune hyperthyroidism which fail to respond to medicaltreatment. Thyroidectomy for uncontrolled hyperthyroid-ism in this age group presents considerable difficulties forthe anaesthetist but our experience suggests that the sameprinciples as those used in hyperthyroid adults are appli-cable. Good preparation with appropriate monitoring anddrug therapy in the postoperative period are essential ifcardiovascular stability is to be achieved throughout theperi-operative period. We have demonstrated that esmololmay be a valuable and safe drug to use in this context both



in the prevention and in the treatment of peri-operativethyrotoxicosis in a young child.

References

1 Foley TP. Thyrotoxicosis in childhood. Paediatric Annals1992; 21: 43–6.

2 Perrild H, Gruters-Kieslich A, Feldt-Rasmussen U, et al.Diagnosis and treatment of thyrotoxicosis in childhood. AEuropean questionnaire study. European Journal ofEndocrinology 1994; 131: 467–73.

3 Kopp P, Van Sande J, Parma J, et al. Brief Report: congenitalhyperthyroidism caused by a mutation in the thyrotrophin-receptor gene. New England Journal of Medicine 1995; 332:150–4.

4 Lavard L, Ranlov I, Perrild H, Anderson O, Jacobsen BB.Incidence of juvenile thyrotoxicosis in Denmark, 1982–1988. A nationwide study. European Journal of Endocrinology1994, 130: 565–8.

5 Caruso DR, Mazzaferri EL. Intervention in Graves’ disease.Choosing among imperfect but effective treatment options.Postgraduate Medicine 1992; 92: 117–24, 128–9, 133–4.

6 Fisher DA, Graves’ disease in children. Current Therapy inEndocrinology and Metabolism 1994, 5: 71–4.

7 Gross G, Lues I. Thyroid dependent alterations of myocardialadrenoceptors and adrenoceptor-mediated responses in therat. Naunyn Schmiedbergs Archives of Pharmacology 1985; 329:427–39.

8 Stiles GL, Lefkowitz RJ. Cardiac adrenergic receptors.Annual Review of Medicine 1984; 35: 149–64.

9 Feely J, Stevenson IH, Crooks J. Increased clearance ofpropranolol in thyrotoxicosis. Annals of Internal Medicine1981; 94: 472–4.

10 Feely J, Forrest A, Gunn A, Hamilton W, Stevenson I,Crooks J. Propranolol dosage in thyrotoxicosis. Journal ofClinical Endocrinology and Metabolism 1980; 51: 658–61.

11 Carruthers SG, Ghosal A, McDevitt DG, Nelson JK, ShanksRG. The assessment of b-adrenoceptor blocking drugs inhyperthyroidism. British Journal of Clinical Pharmacology 1974;1: 93–8.

12 Alderberth A, Stenstrom G, Hasselgren P-O. The selectiveb1-blocking agent metoprolol compared with antithyroiddrug and thyroxine as preoperative treatment of patients withhyperthyroidism. Annals of Surgery 1987; 205: 182–8.

13 Kendrick AH, O’Reilly JF, Laszlo G. Lung function andexercise performance in hyperthyroidism before and aftertreatment. Quarterly Journal of Medicine 1988; 256: 625–7.

14 Ingbar SH. Management of emergencies IX. Thyrotoxicstorm. New England Journal of Medicine 1966; 274: 1252–4.

15 Berman ML, Kuhnert L, Phythyon JM, Holaday DA.Isoflurane and enflurane-induced hepatic necrosis intriiodothyronine-pretreated rats. Anesthesiology 1983; 58:1–5.

16 Trench AJ, Buckley FP, Drummond GB, Arthur GR,Scott DB. Propranolol in thyrotoxicosis. Cardiovascularchanges during thyroidectomy in patients pre-treated withpropranolol. Anaesthesia 1978; 33: 535–9.

17 Stoelting RK, Dierdorf SF. (Compilers) Endocrine diseases.In: Anesthesia and Co-existing Disease. New York: ChurchillLivingstone, 1993: 347–51.

18 Smallridge RC. Metabolic and anatomic thyroidemergencies: a review. Critical Care Medicine 1992; 20: 276–91.

19 Thorne AC, Bedford RF. Esmolol for perioperativemanagement of thyrotoxic goiter. Anesthesiology 1989; 71:291–4.

20 Weist D. Esmolol: a review of its therapeutic efficacy andpharmacokinetic characteristics. Clinical Pharmacokinetics1995; 28: 190–202.

21 Tobias JD, Tobin JR, Maxwell LG. Clinical experiencewith esmolol in infants. Clinical Intensive Care 1990; 1:279–81.

CASE REPORT

Tracheal dilatation complicating prolonged trachealintubation

A. Rhodes, F. J. Lamb, R. M. Grounds and E. D. Bennett

Department of Intensive Care Medicine, St George’s Hospital, Blackshaw Road, Tooting, London SW17 OQT, UK

SummaryA patient with severe acute respiratory distress syndrome requiring prolonged tracheal intubationand mechanical ventilation is described. Tracheal dilatation was noted to have occurred following



an elective surgical tracheostomy. Eventually, the patient was successfully weaned from mechanicalventilation and the tracheostomy tube removed.

Keywords Complications; tracheal dilatation. Intubation; tracheal. Tracheostomy.

......................................................................................Correspondence to: Dr A. RhodesAccepted: 17 August 1996

Complications from tracheal intubation are common [1].This case demonstrates the development of a rare com-plication, tracheal dilatation.

Case history

A 19-year-old Asian woman, suffering from acute respira-tory distress syndrome (ARDS) secondary to a severe,acute asthma attack, received mechanical ventilation for aperiod of 54 days. Her acute lung injury was initiallyassociated with a low lung compliance and a high inspiredoxygen requirement. Positive pressure ventilation wasfacilitated by a pressure-controlled mode of ventilationvia an orotracheal tube. High levels of positive andexpiratory pressure were necessary to ensure adequatetissue oxygenation. After 24 days of tracheal intubation,a surgical tracheostomy was performed at the level of the

third tracheal ring. A size 8.0 mm Portex tracheostomytube was inserted into the trachea.

Her ARDS was complicated by two episodes of bac-terial pneumonia for which she was treated with antibio-tics. She had three fibre-optic bronchoscopies, none ofwhich revealed any problem around the tracheal site.Other relevant therapies for her ARDS included high-dose corticosteroids and inhaled nitric oxide. At no pointduring her illness did she develop any further organ failure.

One week after the tracheostomy had been performed,tracheal dilatation was noted on the chest radiograph(Fig. 1). This gradually progressed and was still evidentat the time of her discharge from hospital 141 days later.There were no problems associated with the trachealdilatation and, despite the patient receiving mechanicalventilation for 54 days, air leakage around the cuff did notoccur.



Figure 1 CT scan showing tracheal dilatation.

Discussion

Complications arising from tracheal intubation arecommon [1]. Traumatic complications usually ariseeither from the tube passing through the larynx or as adirect effect of the tube cuff on the tracheal mucosa.Passage of the tube directly into the trachea via a trach-eostomy avoids direct trauma to the larynx, but it can beassociated with increased damage to the tracheal wall [2].

The tracheal tube has a cuff in order to provide a sealwith the tracheal wall to facilitate positive pressure ventila-tion and to protect the airway from aspiration of secretionsand gastric contents. Problems arise when the pressureinside the cuff exceeds the tracheal mucosal capillarypressure. Ischaemia may then progress to ulceration andnecrosis. This can lead to disruption of the tracheal mucosaand damage to the cartilagenous rings. Tracheal dilatationresults and has the potential to heal with stricture forma-tion and tracheal stenosis [2–4]. Perforation of the tracheaand formation of fistulae into surrounding structures (e.g.the oesophagus) are more serious complications [2].

Prior to the advent of high-volume, low-pressure cuffs,Jacobsen & Jensen described the incidence of trachealdilatation following tracheostomy to be as high as 24%[5]. However, in recent years there have been very fewreports of this potentially serious complication [6]. Thesehigh-volume, low-pressure, cuffed tracheostomy tubeshave substantially reduced the incidence and likelihood

of this problem occurring. In order to prevent mucosaldamage, careful attention must be paid to the volume andpressure of air put into the cuff. It is recommended that thepressure inside the cuff is restricted to less than 25 mmHgand this can be achieved by routine measurement of thecuff pressure [2, 4].

Although this case presents a problem that is rare nowa-days, we feel it is necessary to stress the importance of beingvigilant for old complications, which continue to occurdespite modern technological advances and equipment.

References

1 Gunawardana RH. Experience with tracheostomy inmedical intensive care patients. Postgraduate Medical Journal1992; 68: 338–41.

2 Stone DJ, Bogdonoff DL. Airway considerations in themanagement of patients requiring long-term endotrachealintubation. Anesthesia and Analgesia 1992; 74: 276–87.

3 Bishop MJ. Mechanisms of laryngotracheal injury followingprolonged tracheal intubation. Chest 1989; 96: 185–6.

4 Fryer ME, Marshall RD. Tracheal dilatation. Anaesthesia1976; 31: 470–8.

5 Jacobsen E, Jensen J. Tracheal dilatation. A complication oftracheostomy. Acta Anaesthesiologica Scandinavica 1968; 12:95–102.

6 Prinsley P. View from within . . . Ballooned trachea as aconsequence of intubation. Journal of Laryngology and Otology1992; 106: 561–2.

CASE REPORT

The anaesthetist and the antiphospholipid syndrome

R. Madan,1,2 M. Khoursheed,1,2 R. Kukla,2 M. Al-Mazidi2 and A. Behbehani1,2

1 Department of Surgery, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait2 Mubarak Al-Kabeer Hospital, Kuwait

SummaryAntiphospholipid syndrome is a paradoxical disease state with in vitro prolongation of activatedpartial thromboplastin time and a strong predilection for in vivo thrombosis. The syndrome can beassociated with systemic lupus erythematosus or lupus-like diseases or may be primary, presentingwith thrombotic phenomena in young patients with no risk factors for thrombosis. We presenttwo cases seen in two different settings in the hospital.

Keywords Complications; antiphospholipid syndrome, Hughes syndrome. Blood; lupus anti-coagulant.

......................................................................................Correspondence to: Dr R. MadanAccepted: 16 August 1996



The classical features of the antiphospholipid syndromeinclude arterial and venous thrombosis, livedo reticularis,cerebral involvement (with a strong propensity for cerebralinfarction), neuropsychiatric disturbances, recurrent mis-carriages and thrombocytopenia. A proportion of caseshave hypertension and pulmonary hypertension [1].

Recent observations suggest that the syndrome maywell be one of the commonest acquired hypercoagulablestates and hence the anaesthetist could encounter thesepatients in the intensive care unit (ICU) in thromboticcrisis, or in routine surgery, or as high-risk parturients forlabour or operative delivery. Since it is a relatively recentlydescribed condition, the information on peri-operativemanagement is sparse. We present two cases seen in twodifferent settings in our hospital.

Case histories

Case 1A 20-year-old Kuwaiti woman was diagnosed as havingprimary antiphospholipid syndrome. She had symptoms oftingling and cramps in her right leg found to be due tothrombosis of the posterior tibial artery. She had a pro-longed activated partial thromboplastin time (APTT) andpositive anticardiolipin antibody in moderate titres. Inves-tigations to exclude autoimmune diseases and systemiclupus erythematosus (SLE) were negative. Warfarin 2.5 mgwas prescribed to maintain the international normalisedratio (INR) at 2.0. She was receiving this therapy for 7months and she was free of symptoms from her leg but hermenstrual periods became so heavy that it was difficult tomaintain her haemoglobin level above 6 g.dlÿ1 despiteiron supplements. It was therefore decided to start sub-cutaneous injections of heparin 5000 units 12-hourly andstop warfarin, with the hope of reducing the menstrualbleeding. Within 2 weeks of the warfarin withdrawal shewas admitted to the emergency department in cardiogenicshock secondary to an inferior myocardial infarction. Shedied within 8 h of her admission despite treatment.

Case 2A 32-year-old Egyptian male admitted with obstructivejaundice secondary to postoperative common bile ductstenosis was scheduled for hepaticojejeunostomy. He hadhad excessive bleeding after cholecystectomy 6 monthsearlier but all investigations were normal apart from aprolonged APTT and platelet count of 90 × 109.lÿ1. Inthe postoperative period he developed chest pain and afeeling of suffocation, but an acute myocardial infarctionwas excluded. Eighteen months before he had had a deepvein thrombosis affecting his right leg, superficial throm-bophlebitis of his right arm and a genital ulcer. He had hada similar episode of venous thrombosis 5 years earlier.

On examination he was a mildly jaundiced, moderatelybuilt young man. Apart from a slightly enlarged liver hisgeneral physical examination was normal.

Investigations

Haemoglobin 12 g.lÿ1, platelets 54–92 × 109.lÿ1, APTT69.9 s, prothrombin time (PT) and bleeding time (BT)were normal. Serum bilirubin was 45 mmol.lÿ1, alkalinephosphatase 305 IU.lÿ1, aspartate amino transferase66 IU.lÿ1, alanine amino transferase 63 IU.lÿ1, serumcreatinine 144 mmol.lÿ1. Plasma electrophoresis showeda normal pattern. Coomb’s test, rheumatoid factor andantinuclear antibody were negative. Lupus anticoagulantwas positive. Chest X-ray, ECG and echocardiogram werenormal.

Heparin 5000 units subcutaneously 8-hourly wasstarted and the last dose was given 2 h before surgery.The patient wore antithrombotic stockings, he was keptwarm using a heating mattress and all intravenous fluidswere warmed to body temperature. Prophylactic antibio-tics were given. Surgery under balanced anaesthesia lasted5 h and was uneventful. Heparin 5000 units subcuta-neously was restarted 8 hourly postoperatively. Heremained stable, his platelet count was 110 × 109.lÿ1 andhe had no evidence of bleeding. He was then transferred tothe ward. On the third postoperative day he developed asudden tachycardia of 120 beat.minÿ1, a respiratory rate of40 breath.minÿ1 and cyanosis. Crepitations were heard onthe right side of chest and decreased air entry on the leftside. He was given oxygen by mask and his colourimproved. The patient was transferred to the ICU wherethe blood gases whilst breathing oxygen were PO2

15.1 kPa, PCO2 5.1 kPa, SaO2 97%. The platelet countwas found to be 40 × 109.lÿ1, but there was no oozingfrom the wound. A perfusion scan of the lung wasconsistent with a diagnosis of pulmonary embolism andthe duplex Doppler showed evidence of fresh embolussuperimposed on recanalised old embolus in the rightpopliteal vein. The patient was started on a heparininfusion 24 000 U.dayÿ1 and warfarin 10 mg daily. Hewas stabilised on 15 mg warfarin after 2 months and theINR was 3.0.

Discussion

Antiphospholipid syndrome is associated with the pre-sence of antiphospholipid antibodies, which were firstdetected with the finding of an in vitro coagulationabnormality in patients with SLE [2]. The term ‘lupusanticoagulant’ was used because there was a prolongedclotting time without a specific clotting factor deficiency



[3]. These antibodies also lead to a false positive test forsyphilis [4]. Both phenomena were later linked to anincreased risk of arterial and venous thrombosis in patientswith no other known risk factors. Hughes first referred toit as the ‘anticardiolipin antibody’ syndrome [5, 6] and alsoobserved that patients did not necessarily have SLE inassociation. Asherson [7] described this as ‘antiphospholi-pid syndrome’, but more recently it has been termed‘Hughes syndrome’ [1].

To diagnose a patient as having antiphospholipid syn-drome, one clinical criterion and one laboratory criterionmust be present and antiphospholipid antibodies must bepositive on two occasions more than 3 months apart. Theessential clinical criteria are venous thrombosis, arterialthrombosis, fetal loss and thrombocytopenia. Laboratorycriteria are based on the presence of IgG and IgM anti-cardiolipin antibodies in moderate to high titres andpositive lupus anticoagulant [8].

It has been customary to divide the syndrome into twoforms, primary and secondary. The primary form is notassociated with lupus or lupus-like diseases whereas thesecondary form is accompanied by SLE or lupus-likediseases [9–11].

The first patient, a young woman with no risk factors,developed thrombosis of the posterior tibial artery, waspositive for lupus anticoagulant and had anticardiolipinantibodies in moderate titres, thus satisfying the criteria forprimary antiphospholipid syndrome.

In the second case, a history of repeated deep venousthrombosis and pulmonary embolism in a young man withno obvious risk factors, thrombocytopenia, positive lupusanticoagulant and the presence of IgG anticardiolipinantibodies in high titres, is also highly suggestive of thediagnosis of ‘primary’ antiphospholipid syndrome. Thepatient showed other characteristics of this syndrome suchas a tendency to have repeated episodes of thrombosis atthe same site.

There is a strong predilection for thrombosis in both thearterial and venous systems. About 19% of patients withdeep venous thrombosis/pulmonary embolism have lupusanticoagulant or anticardiolipin antibodies [8]. About 58%[12] of patients with these antibodies will suffer thrombo-sis, although other authors put this figure nearer 30% [13].The commonest site is in the deep veins of the leg. Theother veins reported to be affected are renal, hepatic, portaland mesenteric. Cutaneous ulcers, particularly on themedial malleolus, are also reported.

Arterial thrombosis of the lower limbs, as in the firstcase, is seen in 10% of patients [14–17] and these patientsusually present with claudication and gangrene. Coronarythrombosis with myocardial infarction has also beenreported. The presence of antiphospholipid antibodyshould be suspected in a young patient with myocardial

infarction, particularly if it is a premenopausal womanwith no other risk factors.

Thrombocytopenia has been demonstrated in adultsand children [18–20] although it is not usually severeenough to cause bleeding. There are some reports ofthrombocytopathia and haemolytic anaemia. The secondpatient had a slightly reduced platelet count pre-operativelybut showed no clinical signs of thrombocytopenia. Thecount decreased to 40 × 109.lÿ1 in the postoperativeperiod owing to consumption during thrombus formationbut the patient was still asymptomatic. Bleeding is notcommon, but if it occurs it is usually related to thrombo-cytopenia or hypoprothrombinaemia [21, 22]. Thrombo-cytopenia and qualitative abnormalities of platelets shouldbe looked for.

There is a rapidly progressive, lethal form of this syn-drome termed ‘catastrophic antiphospholipid syndrome’,which results in widespread vascular occlusions and organdysfunction. It can be precipitated by infection, with-drawal of anticoagulants or both. In the first patient, whowas suspected to have this syndrome, the changeover fromwarfarin to heparin could have disturbed the coagulationstatus resulting in this fatal complication.

It is known that these patients can develop thrombosisdespite receiving heparin [23] and this was demonstratedby both patients. A dose of heparin of 10 000–15 000 Usubcutaneously proved not to be adequate for peri-operative thromboprophylaxis in the second patient.

The second patient had marked resistance to warfarin,which is a recognised feature of this disease. Some patientsneed as much as 20 mg to bring the INR up to 3.0 [8].

The characteristic serum markers for this syndromeconsist of a family of autoantibodies which are reactiveagainst different anionic phospholipids required in theformation of prothrombin activator complex in theblood coagulation cascade. During routine coagulationtests in the laboratory the plasma from a large number ofpatients with this syndrome show a prolonged APTT. Thepresence of anticardiolipin antibodies is confirmed byenzyme-linked immunosorbent assay (ELISA) techniqueswith purified cardiolipin. There are some patients whohave a prolonged APTT but are negative for antibodies byELISA and vice versa. When the syndrome is suspected,both sets of tests should be done to detect the highestnumber of patients with antiphospholipid antibody activity.

Peri-operative managementA comprehensive history to elicit the presence of throm-botic episodes, or bleeding, is taken. In the secondary typethe primary disease is evaluated.

A complete coagulation screen including APTT, PT,BT and platelet count should be performed in all patients.Elevation of PT or APTT may be due to antibodies to



various coagulation factors, especially in cases of SLE.There is a considerable risk of bleeding in the presence offactor deficiencies and in these patients regionalanaesthesia is contraindicated. In contrast, an isolatedelevation of the APTT secondary to the presence oflupus anticoagulant, which is unassociated with thrombo-cytopenia or a history or evidence of a bleeding diathesis, isnot a contraindication to regional anaesthesia [24–26]. Inshort, it is important to distinguish between a factorabnormality and isolated lupus anticoagulant, before con-sidering regional anaesthesia. These tests should be donewell in advance of surgery or labour.

Thromboprophylaxis in the peri-operative periodIn a patient with antibody, but no symptoms and a normalcoagulation screen, prophylactic subcutaneous unfraction-ated or low-molecular-weight heparin 5000 units 8-hourly is given in the peri-operative period. In a patientwith a history of recurrent thrombosis, heparin 25 000units subcutaneously in two or three divided doses shouldbe given [8]. The last dose should be given about 2 h priorto surgery. For vascular surgery, an intravenous infusion ofheparin is given to prevent clotting of the grafts.

Intra-operative measures to prevent thrombosis [23]1 Antithrombotic stockings, avoidance of dehydrationand venous sludging, and prevention of hypothermia.Warming of all intravenous fluids.2 Prevention of infection with prophylactic antibiotics.3 Avoidance of drugs which can precipitate thrombosis,such as hydralazine.4 Both whole blood and plasma are preferably avoidedand packed red blood cells are used when needed.

There is nothing in the literature to suggest that anyparticular anaesthetic agent is indicated or contra-indicated.In patients with thromboembolic disease, regional anaes-thesia has been found to be beneficial [27] and the use ofadrenaline with the local anaesthetic is safe [28]. In patientswith antiphospholipid syndrome, the suitability of regionalanaesthesia must be determined for each individual, takinginto account the results of coagulation tests, the clinicalpicture and the advantages compared with general anaes-thesia. This is particularly important in obstetric cases.

Monitoring is determined by pre-operative cardiopul-monary and renal function, the type of surgery and theextent of intra-operative fluid loss anticipated.

PostoperativelyIn asymptomatic patients subcutaneous heparin 5000 U8-hourly is given postoperatively and then stopped.Heparin 25 000 subcutaneously in divided doses is con-tinued in patients with a previous history of thrombosis. Inthe postoperative period warfarin 10 mg by mouth daily is

started as soon as possible, in addition to heparin. TheINR needs to be stabilised at 3.0–3.5 to prevent throm-bosis. After a pulmonary embolus secondary to an idiopathicdeep venous thrombosis warfarin is usually continued forabout 3–6 months, after which it is discontinued. Inpatients with antiphospholipid syndrome there are reportsof repeat thrombosis 2–6 weeks after withdrawal ofwarfarin [29–32], so prolonged warfarin therapy isrecommended.

The patients should be monitored closely for venousthrombosis, pulmonary embolus and catastrophic anti-phospholipid syndrome. If postoperative hypoxia occurs,adult respiratory distress syndrome and pulmonary embol-ism must be considered and the patient should be observedon the ICU. The catastrophic form should be treatedenergetically with early plasmapheresis, immunosuppres-sants and high-dose steroids for a favourable outcome tooccur. Sometimes a dose of heparin as high as 40 000 Uwill not prevent a thrombosis from occurring. The use of adefibrinating enzyme (Russell viper venom) intravenouslymay be life saving since these patients have defectivefibrinolysis [8].

Acknowledgments

We thank Professor A.N. Malaviya, Consultant Rheuma-tologist and Professor K.C. Das, Haematologist in theFaculty of Medicine, University of Kuwait, for helping toprepare the manuscript.

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3 Fenistein DI, Rapaport SI. Acquired inhibitors of bloodcoagulation in five patients. In: Spaet TH, ed. Progress inHemostasis and Thrombosis, Vol. I. New York: Grune &Stratton, 1972: 75–95.

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8 Asherson RA. Antiphospholipid antibodies and syndromes.In: Lahita RG, ed. Systemic Lupus Erythematosus, 2nd edn.New York: Churchill Livingstone, 1992: 587–635.



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