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Meningococcal meningitis after combined spinal-epidural analgesia
International Journal of Obstetric Anesthesia (2003) 12, 183–187 Ó 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0959-289X(03)00014-1
CASE REPORT
Meningococcal meningitis after combined spinal-epidural analgesia A. J. Pinder, M. Dresner Department of Anaesthesia, Leeds General Infirmary, Leeds, UK SUMMARY. We present a case of bacterial meningitis in a 32-year-old parturient following combined spinal-epidural analgesia for labour. The patient made a full recovery with no residual neurological sequelae, but important lessons were learnt. Firstly, investigating obstetricians and physicians were unaware that a combined spinal-epidural technique included an intrathecal component, so did not consider treating organisms that might be acquired by this route. Anaesthetists, on the other hand, in the absence of an isolated organism, saw this as a likely combined spinal-epidural complication. Infectious disease experts eventually diagnosed community-acquired meningococcal meningitis by analysing bacterial deoxyribonucleic acid (DNA) fragments using polymerase chain reaction studies. This test and the management of suspected meningitis in the post-partum period are discussed. Ó 2003 Elsevier Science Ltd. All rights reserved.
INTRODUCTION
CASE REPORT
The combined spinal-epidural (CSE) technique has become increasingly popular for labour analgesia since its introduction in the 1980s. This popularity can be attributed to the spinal component which, if an appropriate drug combination is used, can produce rapid, reliable onset of profound analgesia, with minimal motor blockade. The epidural then provides flexibility for prolonged analgesia and conversion to anaesthesia if needed for operative interventions.1–3 Despite initial support for the technique, worrying case reports of meningitis following CSEs began to appear in the 1990s.4–6 Later papers failed to confirm the earlier findings supporting use of the CSE technique for labour analgesia and, with the fear of meningitis, their routine use was questioned.7;8 We present another case of apparent CSE-related meningitis that taught us some unexpected lessons.
A 32-year-old multiparous patient was admitted to the delivery suite following failed induction of labour for post-maturity. Apart from b-thalassaemia trait, there was no significant medical history, the pregnancy had been normal, and she was apyrexial at the time of admission. Artificial rupture of membranes was performed and a Syntocinon infusion started. Labour proceeded rapidly, prompting the patient to request epidural analgesia. Her midwife, however, advised the use of Entonox at this stage, so an anaesthetist was not called. By the time early decelerations and reduced variability in the cardiotocograph had provoked an obstetrician to site a fetal scalp electrode, the patient had become very distressed and was hyperventilating with Entonox. A sudden loss of consciousness occurred, and medical staff were immediately summoned. On arrival they found the patient to be unrousable but with normal respiration, pulse rate, blood pressure and peripheral perfusion. Immediate management included placement in the left lateral position, administration of oxygen via facemask and stopping the Syntocinon infusion. The patientÕs conscious level gradually improved over the next five minutes and throughout this time blood pressure, heart rate and oxygen saturations were all within normal limits. When able to respond, the patient denied experiencing any chest pain or shortness of breath. In the absence of any symptoms, cardiovascular or respiratory embarrassment, it was concluded that sinister causes of
Accepted December 2002 Dr A.J. Pinder FRCA, Dr M. Dresner FRCA, Department of Anaesthesia, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK. Correspondence to: Dr M. Dresner, Lead Clinician, Obstetric Anaesthesia, Department of Anaesthesia, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK, Tel.: +44-113-392-6684, Mobile Tel.: +410-350-584; Fax: +44-113-392-2645; E-mail: [email protected] 183
184 International Journal of Obstetric Anesthesia the collapse such as amniotic fluid or pulmonary embolus were unlikely. It seemed plausible that pain and hyperventilation had induced a vagal syncope. Another brief, uncomplicated syncope occurred before a neuraxial block was finally placed. The anaesthetist wore a hat, gown and gloves, cleaned the skin with alcohol spray which was allowed to evaporate, but omitted to wear a surgical mask. This was not unit policy, but an oversight during a stressful situation. After skin infiltration with 2% lidocaine at L2/ 3, an uncomplicated spinal was performed, giving 2.5 mL of commercially prepared, premixed 0.1% bupivacaine with 2 lg/mL fentanyl via a 27-gauge Whitacre spinal needle and introducer. Within two contractions, significant analgesia had been produced. A 16-gauge Tuohy needle was then sited at the same interspace. The epidural space was located with ease at 6 cm using lossof-resistance to saline and 4 cm of catheter was passed into the epidural space. Because of some residual pain and an anticipated instrumental delivery, 10 mL of 1.5% lidocaine was given epidurally, providing complete analgesia within 20 min. This concentration was the only preservative-free lidocaine solution available in our unit at that time. In fact, active pushing produced a normal vaginal delivery of a healthy baby boy soon afterwards. On routine follow-up by an anaesthetist the next morning the patient described her pain relief during labour and delivery as very effective. Her motor block was minimal, overall satisfaction was excellent and she had no complaints. However, later that morning the obstetric senior house officer was asked to see the patient. By now she was complaining of severe frontal headache associated with vomiting and drowsiness. No neck stiffness, photophobia, rash or pyrexia were noted. Despite the similarity of these symptoms to post dural puncture headache, the anaesthetists were not informed. She was given diclofenac and prochlorperazine and her symptoms settled temporarily. A few hours later the patient was found to be difficult to rouse and irritable. Her headache and vomiting had returned and she was reviewed again by the obstetric team who found her to be uncooperative and refusing clinical examination. In an informal corridor consultation, an obstetric anaesthetist ventured that the clinical picture demanded the exclusion of intracranial pathology. At this stage the formal opinion of a neurologist was sought. The diagnosis of post-partum migraine was strongly considered, but a computed tomography (CT) scan was ordered to exclude more sinister pathology such as venous sinus thrombosis or an intracerebral bleed. During the twohour wait for CT availability, the patientÕs systolic blood pressure fell to 87 mm Hg, and her Glasgow Coma Scale (GCS) fell to 11. Intravenous fluid resuscitation improved both her blood pressure and GCS, but she remained acutely confused and too restless to allow the
CT scan to be performed. The non-obstetric anaesthetic acute team were contacted and provided general anaesthesia for the scan. This revealed no haemorrhage, oedema or focal collection. The temporal horns were reported to be prominent but there was no hydrocephalus. Contrast did not reveal any focal lesions but there was sinus enhancement. A magnetic resonance imaging (MRI) scan was recommended to further exclude sagittal sinus thrombosis. Over the subsequent hours her severe, throbbing headache, nausea, vomiting, and photophobia became associated with a pyrexia of 38.1°C. Meningitis became an obvious possibility, and the neurologist was asked to review her. By now the patient was having difficulty with speech. A catheter urine specimen was consistent with a urinary tract infection (white cell count > 50/ mm3 , red cell count > 1/mm3 , 1 + epithelial cells). The neurologist concluded that the patient was suffering from migraine with dysphasia and had a concomitant urinary tract infection. Antibiotics, regular paracetamol and antiemetics were advised. Symptoms continued and an increasing pyrexia of 38.4 °C and a C-reactive protein (CRP) of 211 mg/L prompted a request for a further neurology review and lumbar puncture. This revealed a cerebrospinal fluid (CSF) pressure of 22 cm water and a slightly cloudy appearance. White cell counts were 4560 and 4800/mm3 CSF in 2 samples taken with 90% polymorphs. Protein was 1.97 g/L and glucose 1.1 mmol/L. There were no organisms seen on Gram staining of the CSF and no organisms were subsequently cultured. As these findings were consistent with bacterial meningitis, cefotaxime therapy was started and the patient transferred to the local infectious diseases unit. In the pursuit of the responsible organism, the infectious diseases team asked the obstetricians if a dural tap had occurred. In the presence of dural puncture, antistaphylococcal therapy, such as flucloxacillin, would have been recommended by them as an additional regimen to cover infections caused by any skin commensals introduced. The obstetricians did not appreciate that a CSE includes a deliberate dural puncture, and an anaesthetic opinion was, once again, not sought. Cefotaxime was continued and amoxycillin was added to cover potential Listeria organisms. The patientÕs symptoms gradually improved over the subsequent three days, during which a blood transfusion was given. Eventually CSF polymerase chain reaction (PCR) studies proved positive for Neisseria meningitidis strain W135 and the antibiotic regimen was changed to benzylpenicillin, with rifampicin given to eliminate nasal carriage. Acute and convalescent meningococcal serologies were negative. The patient made a full recovery with no residual neurological sequelae and was discharged home the following week.
Meningococcal meningitis after combined spinal-epidural analgesia 185 DISCUSSION There are three clear lessons from this case. The first relates to the fact that non-anaesthetists did not understand the CSE technique, and so direct contamination of the CSF was not considered. Complicated obstetric cases must be managed with a multidisciplinary approach. The second lesson is that, but for the CSF polymerase chain reaction studies, we would probably have reported this as another case of meningitis associated with the CSE technique. In this instance, CSE was exonerated, as was the anaesthetist who forgot to don a surgical mask. Finally, a case of community-acquired bacterial meningitis proved embarrassingly difficult to diagnose, largely because it presented in the unusual context of a maternity unit. Meningitis may occur during pregnancy or in the post-partum period, unrelated to epidurals and spinals. Coincidental infections may be primary, most commonly due to Streptococcus pneumoniae, Neisseria meningitidis or Haemophilus influenzae, or secondary to infective endocarditis.9 There are numerous reports of meningitis following regional anaesthetic techniques in obstetric patients. Both epidural and spinal techniques alone and in combination, for labour analgesia or operative procedures, have been followed by infective sequelae.4–6;10–17 Organisms have not been isolated in all cases, this often being attributed to prior antibiotic usage. Those reported include various streptococci,4;5;10–12 staphylococci6 and pseudomonas.13 The CSE technique is thought to be associated with an increased risk of meningitis compared to an epidural alone, and in our unit it is reserved for women in advanced labour or in great distress, using separate needles for the two components. This approach is taken because we believe it to be the quickest way to achieve analgesia, and standard needles can be used. The relative risk of meningitis following CSE compared to single or no central neuraxial block is unknown.18 During a CSE the dura is punctured deliberately and then a foreign body, an epidural catheter, is placed nearby. This is a potential focus of infection, especially following a bacteraemic episode, and the epidural catheter then lies close to the dural hole. Most cases of meningitis following regional anaesthesia occur after intentional or accidental dural puncture.19 Penetration of the dura bypasses the bodyÕs natural defences and there are then two possible mechanisms for the introduction of infection.20 Firstly, microscopic bleeding caused by needle trauma may allow contamination of the subarachnoid space in a bacteraemic patient. Failure of aseptic techniques is the second mechanism, with direct introduction of bacteria or other particulate matter into the sterile cerebrospinal fluid. This may be due to inadequate sterilisation or subsequent contamination of equipment and anaesthetic
drugs, droplets from oropharyngeal secretions of attendant staff or skin contaminants due to inadequate skin preparation. Epidural abscesses are more common than meningitis following an epidural, unless there is an inadvertent dural tap and/or treatment with an epidural blood patch.21 Meticulous aseptic technique when performing epidurals and spinals is imperative, although if performed outside the theatre environment in a delivery room, strict asepsis in a very distressed patient can be difficult to achieve. The anaesthetist should wash hands, gown and wear sterile gloves. The wearing of a facemask is also recommended. Most cases of ÔanaestheticÕ meningitis are due to Streptococcus viridans, which is commonly found in the upper respiratory and gastrointestinal tracts and can easily be transmitted by droplet infection from attending staff to the patient. Wearing a facemask should prevent this mode of transmission and studies have shown that facemasks prevent forward dispersal of organisms from the upper airway and downward dispersal during talking and head turning. The alternative would be to not talk to the patient whilst siting the epidural or spinal but this would be inappropriate.22;23 Despite this, a postal survey of members of the Obstetric Anaesthetists Association in 1996 found that over half the anaesthetists do not routinely wear facemasks when performing regional anaesthetic techniques for a variety of reasons.24 The back should be prepared by wiping or spraying with a solution such as chlorhexidine and allowing it to dry. Any excess fluid should be wiped off to prevent its introduction into the epidural or subarachnoid space and causing chemical irritation. Sterile drapes should then be applied.25 If bacterial meningitis is suspected in a patient, prompt treatment with the appropriate antibiotics should allow a good chance of rapid recovery without any neurological sequelae. Clinical signs such as headache, pyrexia and vomiting are supported by lumbar puncture findings of cloudy, high pressure CSF with a raised white cell count, predominance of polymorphs, high protein, low glucose and the presence of organisms seen on gram staining and microscopy. Subsequent culture of organisms from the CSF or blood then allows confirmation of the diagnosis. Difficulties arise when there are non-specific or atypical clinical signs or there has been prior antibiotic treatment. In the latter case microscopy and culture are usually negative. Also, meningitis following spinals is often caused by unusual or nosocomial organisms which can be difficult to identify with routine laboratory cultures.26 In these circumstances there may also be a misdiagnosis of aseptic meningitis, due to detergent or disinfectant contaminated equipment. This form of meningitis is now less common than in the past following the widespread introduction of disposable equipment and improvements in sterilisation tech-
186 International Journal of Obstetric Anesthesia niques.6;27 Antibiotic treatment should therefore cover organisms known to cause meningitis and also more unusual organisms if there has been breach of the dura. With the recommendation of early antibiotic administration to any patient with suspected meningitis,28 the likelihood of obtaining positive blood or CSF cultures has fallen from 50% and 90%, respectively, to less than 5%. This is due to either low numbers or non-viability of organisms in these clinical samples after antibiotic administration, as in our patient. In England and Wales, the Public Health Laboratory ServiceÕs meningococcal reference unit in Manchester has set up a national service that uses PCR to confirm suspected cases of meningococcal infection.29 Clinical specimens, either an early EDTA blood sample or CSF within 48 h of antibiotic treatment, are sent there from hospital laboratories throughout England and Wales. PCR is used to detect meningococcal DNA in samples from patients who are culture negative because of prior antibiotic treatment or death of organisms in samples during transport to laboratories. Thus it does not depend on viable organisms being present. The tiny quantities of microbial DNA in clinical specimens are generally too low for detection and measurement by standard means. PCR allows the production of larger quantities of DNA by nucleic acid amplification (or copying repeatedly) of specific DNA insertion sequences, using polymerase enzymes and oligonucleotide primers. The PCR products are then detected, identified and quantified, in the past using enzyme-linked immunosorbent assay (ELISA) techniques, but more recently by a commercial ÔTaqmanÕ system which uses a fluorescently labelled probe to detect, confirm and quantify the PCR product as it is being generated in real time.30 This reduces assay times to only a few hours, enabling notification of initial screening results to laboratories in less than a day. The use of a closed tube format also reduces the potential risk of false positive results from contaminating extraneous meningococcal DNA or PCR product. After screening by the ctrA Taqman assay, which detects the capsular transferase gene, all positives are subsequently confirmed by amplification of the siaD gene for serogroup identity of the organism in question.29–32 PCR has been reported to be a rapid, sensitive and specific test for detecting meningococcal DNA in both CSF33;34 and peripheral blood.35 Its use in our patient allowed identification of the causative agent, which had not been detected by other means, and absolved the anaesthetist as the cause of the meningitis. An earlier case report highlighted the dangers associated with a missed diagnosis of meningitis.36 A parturient presented with headache, vomiting and fever two days after an uncomplicated epidural for labour. Endometritis was diagnosed and intravenous antibiotics given. The patientÕs condition rapidly deteriorated and she died
in intensive care a few weeks later. No organisms were identified on Gram stain or culture of blood and CSF and meningitis was not considered as a diagnosis until it was too late. Fortunately, our patient had a successful outcome but there was the potential for a more tragic result. There are many causes of headache in the peripartum period. Obstetricians are strongly focussed on preeclampsia and anaesthetists on post dural puncture headache. Coincidental causes unrelated to obstetrics, such as cerebral tumours and meningitis, might be overlooked because of their rarity in the obstetric context. This case report reminds us to exclude the unusual sinister causes of headache early and to work with a multidisciplinary team approach, and illustrates the value of sophisticated microbiological studies.
REFERENCES 1. Buxbaum J L. Combined spinal-epidural for labor analgesia. Curr Opin Anaesthesiol 1999; 12: 295–298. 2. Collis R E, Baxandall M L, Srikantharajah I D, Edge G, Kadim M Y, Morgan B M. Combined spinal-epidural analgesia: technique, management and outcome of 300 mothers. International Journal of Obstetric Anesthesia 1994; 3: 75–81. 3. Collis R E, Davies D W, Aveling W. Randomised comparison of combined spinal-epidural and standard epidural analgesia in labour. Lancet 1995; 345: 1413–1416. 4. Cascio M, Heath G. Meningitis following a combined spinal-epidural technique in a labouring parturient. Can J Anaesth 1996; 43: 399–402. 5. Bouhemad B, Dounas M, Mercier F J, Benhamou D. Bacterial meningitis following combined spinal-epidural analgesia for labour. Anaesthesia 1998; 53: 292–295. 6. Harding S A, Collis R E, Morgan B M. Meningitis after combined spinal-epidural in obstetrics. Br J Anaesth 1994; 73: 545–547. 7. Dresner M, Bamber J, Calow C, Freeman J, Charlton P. Comparison of low-dose epidural with combined spinal-epidural for labour. Br J Anaesth 1999; 83: 756–760. 8. Nickells J S, Vaughan D J A, Lillywhite N K, Loughnan B, Hasan M, Robinson P N. Speed of onset of regional analgesia in labour: a comparison of the epidural and spinal routes. Anaesthesia 2000; 55: 17–20. 9. Goldstein P J. Neurological Disorders of Pregnancy. New York: Futura Publishing Company, 1986. 10. Davis L, Hargreaves C, Robinson P N. Postpartum meningitis. Anaesthesia 1993; 48: 788–789. 11. Ready L B, Helfer D. Bacterial meningitis in parturients after epidural anesthesia. Anesthesiology 1989; 71: 988–990. 12. Berga S, Trierweiler M W. Bacterial meningitis following epidural anesthesia for vaginal delivery: a case report. Obstet Gynecol 1989; 74: 437–439. 13. Corbett J J, Rosenstein B J. Pseudomonas meningitis related to spinal anesthesia. Neurology 1971; 21: 946–950. 14. Newton J A, Lesnik I K, Kennedy C A. Streptococcus salivarius meningitis following spinal anesthesia. Clin Infect Dis 1994; 18: 840–841. 15. Lee J J, Parry H. Bacterial meningitis following spinal anaesthesia for caesarean section. Br J Anaesth 1991; 66: 383–386. 16. Donnelly T, Koper M, Mallaiah S. Meningitis following spinal anaesthesia coincidental infection? International Journal of Obstetric Anesthesia 1998; 7: 170–172. 17. Roberts S P, Petts H V. Meningitis after obstetric spinal anaesthesia. Anaesthesia 1990; 45: 376–377. 18. Macarthur A. Management of controversies in obstetric anesthesia. Can J Anaesth 1999; 46: R111–1116.
Meningococcal meningitis after combined spinal-epidural analgesia 187 19. Burke D, Wildsmith J A W. Meningitis after spinal anaesthesia (editorial). Br J Anaesth 1997; 78: 635–636. 20. Cook T M. CSE techniques. Anaesthesia 2000; 55: 42–64. 21. Loo C C, Dahlgren G, Irestedt L. Neurological complications in obstetric regional anaesthesia. International Journal of Obstetric Anesthesia 2000; 9: 99–124. 22. McLure H A, Talboys C A, Yentis S M, Azadian B S. Surgical facemasks and downward dispersal of bacteria. Anaesthesia 1998; 53: 624–626. 23. Philips B J, Fergusson S, Armstrong P, Anderson F M, Wildsmith J A W. Surgical facemasks are effective in reducing bacterial contamination caused by dispersal from the upper airway. Br J Anaesth 1992; 69: 407–408. 24. Panikkar K K, Yentis S M. Wearing of masks for obstetric regional anaesthesia. Anaesthesia 1996; 51: 398–400. 25. Smedstad K G. Infection after central neuroaxial blockade (editorial). Can J Anaesth 1997; 44: 235–238. 26. Kilpatrick M E, Girgis N I. Meningitis – a complication of spinal anesthesia. Anesth Analg 1983; 62: 513–515. 27. Bert A A, Laasberg L H. Aseptic meningitis following spinal anesthesia-a complication of the past? Anesthesiology 1985; 62: 674–677. 28. Begg N, Cartwright K A V, Cohen J, et al. Consensus statement on diagnosis, investigation, treatment and prevention of acute
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bacterial meningitis in immunocompetent adults. J Infect 1999; 39: 1–15. Kaczmarski E B, Ragunathan P L, Marsh J, Gray S J, Guiver M. Creating a national service for the diagnosis of meningococcal disease by the polymerase chain reaction. Comm Dis Pub Hlth 1998; 1: 54–56. Heid C A, Stevens J, Livak K J, Williams P M. Real time quantitative PCR. Genome Res 1996; 6: 986–994. Fredricks D N, Relman D A. Application of polymerase chain reaction to the diagnosis of infectious diseases. Clin Infect Dis 1999; 29: 475–488. Fox A J. Nucleic acid technologies and meningococcal infection. J Infect 2001; 42: 100–103. Ni H, Knight A I, Cartwright K, Palmer W H, McFadden J. Polymerase chain reaction for diagnosis of meningococcal meningitis. Lancet 1992; 340: 1432–1434. Kristiansen B, Ask E, Jenkins A, Fermer C, Radstrom P, Skold O. Rapid diagnosis of meningococcal meningitis by polymerase chain reaction. Lancet 1991; 337: 1568–1569. Newcombe J, Cartwright K, Palmer W H, McFadden J. PCR of peripheral blood for diagnosis of meningococcal disease. J Clin Microbiol 1996; 34: 1637–1640. Choy J C. Mortality from peripartum meningitis. Anaesth Intensive Care 2000; 28: 328–330.
CASE REPORT
Meningococcal meningitis after combined spinal-epidural analgesia A. J. Pinder, M. Dresner Department of Anaesthesia, Leeds General Infirmary, Leeds, UK SUMMARY. We present a case of bacterial meningitis in a 32-year-old parturient following combined spinal-epidural analgesia for labour. The patient made a full recovery with no residual neurological sequelae, but important lessons were learnt. Firstly, investigating obstetricians and physicians were unaware that a combined spinal-epidural technique included an intrathecal component, so did not consider treating organisms that might be acquired by this route. Anaesthetists, on the other hand, in the absence of an isolated organism, saw this as a likely combined spinal-epidural complication. Infectious disease experts eventually diagnosed community-acquired meningococcal meningitis by analysing bacterial deoxyribonucleic acid (DNA) fragments using polymerase chain reaction studies. This test and the management of suspected meningitis in the post-partum period are discussed. Ó 2003 Elsevier Science Ltd. All rights reserved.
INTRODUCTION
CASE REPORT
The combined spinal-epidural (CSE) technique has become increasingly popular for labour analgesia since its introduction in the 1980s. This popularity can be attributed to the spinal component which, if an appropriate drug combination is used, can produce rapid, reliable onset of profound analgesia, with minimal motor blockade. The epidural then provides flexibility for prolonged analgesia and conversion to anaesthesia if needed for operative interventions.1–3 Despite initial support for the technique, worrying case reports of meningitis following CSEs began to appear in the 1990s.4–6 Later papers failed to confirm the earlier findings supporting use of the CSE technique for labour analgesia and, with the fear of meningitis, their routine use was questioned.7;8 We present another case of apparent CSE-related meningitis that taught us some unexpected lessons.
A 32-year-old multiparous patient was admitted to the delivery suite following failed induction of labour for post-maturity. Apart from b-thalassaemia trait, there was no significant medical history, the pregnancy had been normal, and she was apyrexial at the time of admission. Artificial rupture of membranes was performed and a Syntocinon infusion started. Labour proceeded rapidly, prompting the patient to request epidural analgesia. Her midwife, however, advised the use of Entonox at this stage, so an anaesthetist was not called. By the time early decelerations and reduced variability in the cardiotocograph had provoked an obstetrician to site a fetal scalp electrode, the patient had become very distressed and was hyperventilating with Entonox. A sudden loss of consciousness occurred, and medical staff were immediately summoned. On arrival they found the patient to be unrousable but with normal respiration, pulse rate, blood pressure and peripheral perfusion. Immediate management included placement in the left lateral position, administration of oxygen via facemask and stopping the Syntocinon infusion. The patientÕs conscious level gradually improved over the next five minutes and throughout this time blood pressure, heart rate and oxygen saturations were all within normal limits. When able to respond, the patient denied experiencing any chest pain or shortness of breath. In the absence of any symptoms, cardiovascular or respiratory embarrassment, it was concluded that sinister causes of
Accepted December 2002 Dr A.J. Pinder FRCA, Dr M. Dresner FRCA, Department of Anaesthesia, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK. Correspondence to: Dr M. Dresner, Lead Clinician, Obstetric Anaesthesia, Department of Anaesthesia, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK, Tel.: +44-113-392-6684, Mobile Tel.: +410-350-584; Fax: +44-113-392-2645; E-mail: [email protected] 183
184 International Journal of Obstetric Anesthesia the collapse such as amniotic fluid or pulmonary embolus were unlikely. It seemed plausible that pain and hyperventilation had induced a vagal syncope. Another brief, uncomplicated syncope occurred before a neuraxial block was finally placed. The anaesthetist wore a hat, gown and gloves, cleaned the skin with alcohol spray which was allowed to evaporate, but omitted to wear a surgical mask. This was not unit policy, but an oversight during a stressful situation. After skin infiltration with 2% lidocaine at L2/ 3, an uncomplicated spinal was performed, giving 2.5 mL of commercially prepared, premixed 0.1% bupivacaine with 2 lg/mL fentanyl via a 27-gauge Whitacre spinal needle and introducer. Within two contractions, significant analgesia had been produced. A 16-gauge Tuohy needle was then sited at the same interspace. The epidural space was located with ease at 6 cm using lossof-resistance to saline and 4 cm of catheter was passed into the epidural space. Because of some residual pain and an anticipated instrumental delivery, 10 mL of 1.5% lidocaine was given epidurally, providing complete analgesia within 20 min. This concentration was the only preservative-free lidocaine solution available in our unit at that time. In fact, active pushing produced a normal vaginal delivery of a healthy baby boy soon afterwards. On routine follow-up by an anaesthetist the next morning the patient described her pain relief during labour and delivery as very effective. Her motor block was minimal, overall satisfaction was excellent and she had no complaints. However, later that morning the obstetric senior house officer was asked to see the patient. By now she was complaining of severe frontal headache associated with vomiting and drowsiness. No neck stiffness, photophobia, rash or pyrexia were noted. Despite the similarity of these symptoms to post dural puncture headache, the anaesthetists were not informed. She was given diclofenac and prochlorperazine and her symptoms settled temporarily. A few hours later the patient was found to be difficult to rouse and irritable. Her headache and vomiting had returned and she was reviewed again by the obstetric team who found her to be uncooperative and refusing clinical examination. In an informal corridor consultation, an obstetric anaesthetist ventured that the clinical picture demanded the exclusion of intracranial pathology. At this stage the formal opinion of a neurologist was sought. The diagnosis of post-partum migraine was strongly considered, but a computed tomography (CT) scan was ordered to exclude more sinister pathology such as venous sinus thrombosis or an intracerebral bleed. During the twohour wait for CT availability, the patientÕs systolic blood pressure fell to 87 mm Hg, and her Glasgow Coma Scale (GCS) fell to 11. Intravenous fluid resuscitation improved both her blood pressure and GCS, but she remained acutely confused and too restless to allow the
CT scan to be performed. The non-obstetric anaesthetic acute team were contacted and provided general anaesthesia for the scan. This revealed no haemorrhage, oedema or focal collection. The temporal horns were reported to be prominent but there was no hydrocephalus. Contrast did not reveal any focal lesions but there was sinus enhancement. A magnetic resonance imaging (MRI) scan was recommended to further exclude sagittal sinus thrombosis. Over the subsequent hours her severe, throbbing headache, nausea, vomiting, and photophobia became associated with a pyrexia of 38.1°C. Meningitis became an obvious possibility, and the neurologist was asked to review her. By now the patient was having difficulty with speech. A catheter urine specimen was consistent with a urinary tract infection (white cell count > 50/ mm3 , red cell count > 1/mm3 , 1 + epithelial cells). The neurologist concluded that the patient was suffering from migraine with dysphasia and had a concomitant urinary tract infection. Antibiotics, regular paracetamol and antiemetics were advised. Symptoms continued and an increasing pyrexia of 38.4 °C and a C-reactive protein (CRP) of 211 mg/L prompted a request for a further neurology review and lumbar puncture. This revealed a cerebrospinal fluid (CSF) pressure of 22 cm water and a slightly cloudy appearance. White cell counts were 4560 and 4800/mm3 CSF in 2 samples taken with 90% polymorphs. Protein was 1.97 g/L and glucose 1.1 mmol/L. There were no organisms seen on Gram staining of the CSF and no organisms were subsequently cultured. As these findings were consistent with bacterial meningitis, cefotaxime therapy was started and the patient transferred to the local infectious diseases unit. In the pursuit of the responsible organism, the infectious diseases team asked the obstetricians if a dural tap had occurred. In the presence of dural puncture, antistaphylococcal therapy, such as flucloxacillin, would have been recommended by them as an additional regimen to cover infections caused by any skin commensals introduced. The obstetricians did not appreciate that a CSE includes a deliberate dural puncture, and an anaesthetic opinion was, once again, not sought. Cefotaxime was continued and amoxycillin was added to cover potential Listeria organisms. The patientÕs symptoms gradually improved over the subsequent three days, during which a blood transfusion was given. Eventually CSF polymerase chain reaction (PCR) studies proved positive for Neisseria meningitidis strain W135 and the antibiotic regimen was changed to benzylpenicillin, with rifampicin given to eliminate nasal carriage. Acute and convalescent meningococcal serologies were negative. The patient made a full recovery with no residual neurological sequelae and was discharged home the following week.
Meningococcal meningitis after combined spinal-epidural analgesia 185 DISCUSSION There are three clear lessons from this case. The first relates to the fact that non-anaesthetists did not understand the CSE technique, and so direct contamination of the CSF was not considered. Complicated obstetric cases must be managed with a multidisciplinary approach. The second lesson is that, but for the CSF polymerase chain reaction studies, we would probably have reported this as another case of meningitis associated with the CSE technique. In this instance, CSE was exonerated, as was the anaesthetist who forgot to don a surgical mask. Finally, a case of community-acquired bacterial meningitis proved embarrassingly difficult to diagnose, largely because it presented in the unusual context of a maternity unit. Meningitis may occur during pregnancy or in the post-partum period, unrelated to epidurals and spinals. Coincidental infections may be primary, most commonly due to Streptococcus pneumoniae, Neisseria meningitidis or Haemophilus influenzae, or secondary to infective endocarditis.9 There are numerous reports of meningitis following regional anaesthetic techniques in obstetric patients. Both epidural and spinal techniques alone and in combination, for labour analgesia or operative procedures, have been followed by infective sequelae.4–6;10–17 Organisms have not been isolated in all cases, this often being attributed to prior antibiotic usage. Those reported include various streptococci,4;5;10–12 staphylococci6 and pseudomonas.13 The CSE technique is thought to be associated with an increased risk of meningitis compared to an epidural alone, and in our unit it is reserved for women in advanced labour or in great distress, using separate needles for the two components. This approach is taken because we believe it to be the quickest way to achieve analgesia, and standard needles can be used. The relative risk of meningitis following CSE compared to single or no central neuraxial block is unknown.18 During a CSE the dura is punctured deliberately and then a foreign body, an epidural catheter, is placed nearby. This is a potential focus of infection, especially following a bacteraemic episode, and the epidural catheter then lies close to the dural hole. Most cases of meningitis following regional anaesthesia occur after intentional or accidental dural puncture.19 Penetration of the dura bypasses the bodyÕs natural defences and there are then two possible mechanisms for the introduction of infection.20 Firstly, microscopic bleeding caused by needle trauma may allow contamination of the subarachnoid space in a bacteraemic patient. Failure of aseptic techniques is the second mechanism, with direct introduction of bacteria or other particulate matter into the sterile cerebrospinal fluid. This may be due to inadequate sterilisation or subsequent contamination of equipment and anaesthetic
drugs, droplets from oropharyngeal secretions of attendant staff or skin contaminants due to inadequate skin preparation. Epidural abscesses are more common than meningitis following an epidural, unless there is an inadvertent dural tap and/or treatment with an epidural blood patch.21 Meticulous aseptic technique when performing epidurals and spinals is imperative, although if performed outside the theatre environment in a delivery room, strict asepsis in a very distressed patient can be difficult to achieve. The anaesthetist should wash hands, gown and wear sterile gloves. The wearing of a facemask is also recommended. Most cases of ÔanaestheticÕ meningitis are due to Streptococcus viridans, which is commonly found in the upper respiratory and gastrointestinal tracts and can easily be transmitted by droplet infection from attending staff to the patient. Wearing a facemask should prevent this mode of transmission and studies have shown that facemasks prevent forward dispersal of organisms from the upper airway and downward dispersal during talking and head turning. The alternative would be to not talk to the patient whilst siting the epidural or spinal but this would be inappropriate.22;23 Despite this, a postal survey of members of the Obstetric Anaesthetists Association in 1996 found that over half the anaesthetists do not routinely wear facemasks when performing regional anaesthetic techniques for a variety of reasons.24 The back should be prepared by wiping or spraying with a solution such as chlorhexidine and allowing it to dry. Any excess fluid should be wiped off to prevent its introduction into the epidural or subarachnoid space and causing chemical irritation. Sterile drapes should then be applied.25 If bacterial meningitis is suspected in a patient, prompt treatment with the appropriate antibiotics should allow a good chance of rapid recovery without any neurological sequelae. Clinical signs such as headache, pyrexia and vomiting are supported by lumbar puncture findings of cloudy, high pressure CSF with a raised white cell count, predominance of polymorphs, high protein, low glucose and the presence of organisms seen on gram staining and microscopy. Subsequent culture of organisms from the CSF or blood then allows confirmation of the diagnosis. Difficulties arise when there are non-specific or atypical clinical signs or there has been prior antibiotic treatment. In the latter case microscopy and culture are usually negative. Also, meningitis following spinals is often caused by unusual or nosocomial organisms which can be difficult to identify with routine laboratory cultures.26 In these circumstances there may also be a misdiagnosis of aseptic meningitis, due to detergent or disinfectant contaminated equipment. This form of meningitis is now less common than in the past following the widespread introduction of disposable equipment and improvements in sterilisation tech-
186 International Journal of Obstetric Anesthesia niques.6;27 Antibiotic treatment should therefore cover organisms known to cause meningitis and also more unusual organisms if there has been breach of the dura. With the recommendation of early antibiotic administration to any patient with suspected meningitis,28 the likelihood of obtaining positive blood or CSF cultures has fallen from 50% and 90%, respectively, to less than 5%. This is due to either low numbers or non-viability of organisms in these clinical samples after antibiotic administration, as in our patient. In England and Wales, the Public Health Laboratory ServiceÕs meningococcal reference unit in Manchester has set up a national service that uses PCR to confirm suspected cases of meningococcal infection.29 Clinical specimens, either an early EDTA blood sample or CSF within 48 h of antibiotic treatment, are sent there from hospital laboratories throughout England and Wales. PCR is used to detect meningococcal DNA in samples from patients who are culture negative because of prior antibiotic treatment or death of organisms in samples during transport to laboratories. Thus it does not depend on viable organisms being present. The tiny quantities of microbial DNA in clinical specimens are generally too low for detection and measurement by standard means. PCR allows the production of larger quantities of DNA by nucleic acid amplification (or copying repeatedly) of specific DNA insertion sequences, using polymerase enzymes and oligonucleotide primers. The PCR products are then detected, identified and quantified, in the past using enzyme-linked immunosorbent assay (ELISA) techniques, but more recently by a commercial ÔTaqmanÕ system which uses a fluorescently labelled probe to detect, confirm and quantify the PCR product as it is being generated in real time.30 This reduces assay times to only a few hours, enabling notification of initial screening results to laboratories in less than a day. The use of a closed tube format also reduces the potential risk of false positive results from contaminating extraneous meningococcal DNA or PCR product. After screening by the ctrA Taqman assay, which detects the capsular transferase gene, all positives are subsequently confirmed by amplification of the siaD gene for serogroup identity of the organism in question.29–32 PCR has been reported to be a rapid, sensitive and specific test for detecting meningococcal DNA in both CSF33;34 and peripheral blood.35 Its use in our patient allowed identification of the causative agent, which had not been detected by other means, and absolved the anaesthetist as the cause of the meningitis. An earlier case report highlighted the dangers associated with a missed diagnosis of meningitis.36 A parturient presented with headache, vomiting and fever two days after an uncomplicated epidural for labour. Endometritis was diagnosed and intravenous antibiotics given. The patientÕs condition rapidly deteriorated and she died
in intensive care a few weeks later. No organisms were identified on Gram stain or culture of blood and CSF and meningitis was not considered as a diagnosis until it was too late. Fortunately, our patient had a successful outcome but there was the potential for a more tragic result. There are many causes of headache in the peripartum period. Obstetricians are strongly focussed on preeclampsia and anaesthetists on post dural puncture headache. Coincidental causes unrelated to obstetrics, such as cerebral tumours and meningitis, might be overlooked because of their rarity in the obstetric context. This case report reminds us to exclude the unusual sinister causes of headache early and to work with a multidisciplinary team approach, and illustrates the value of sophisticated microbiological studies.
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