Hepatobiliary Table 21.5.1 Normal values for liver function tests (values may differ slightly between lab oratories) Bone Alanine aminotransferase Aspartate aminotransferase Alkaline phosphatase -Glutamyltransf erase Bilirubin Albumin Prothrombin time Ammonia Lactate 3 \200\22335 IU/l 3 \200\22335IU/l 30 \200\223300IU/l 10 \200\22350IU/l 3 \200\22317 mol/l 35 \200\22348g/dl 12 \200\22316s 15 \200\22345mcg/dl <1.5mmol/l Intestine Placenta Other 357 CHAPTER 21.5 Abnormal liver function tests Table 21.5.4 Causes of hyperlactataemia Table 21.5.5 Suggested initial investigations for patients with acute liver injury Hypotension/cardiac arrest Regional infarction Septic shock Poisoning (e.g. ethylene glycol , methanol) Liver failure Diabetes mellitus Renal failure Drugs, e.g. metformin Hematologic al malignancy Pancreatitis Thiamine de \201 ciency Glucose-6-dehydrogenase de \201 ciency Short bowel syndrome (D-lactate) Type A Urea and electrolytes Glucose Liver function tests (bilirubin, ALT/AST, alkaline phosphatas e, GT, albumin) Creatine kinase Full blood count Prothrombin time/INR Arterial blood gas Arterial lactate Paracetamol levels Blood group Toxicology screen Viral hepatitis markers (anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HEV IgM, anti-HCV Ab, anti-EBV IgM, anti-CMV IgM) Autoimmune markers (immunoglobulin, antinuclear antibody, anti-smooth muscle antibody) Caer uloplasmin Pregnancy test Type B Clotting factors Almost all the proteins that make up the coagulation cas- cade are produce d by the liver. The PT is sensitive to low levels of factor VII, which, with a short half-l ife of 4 \200\2236h, is a sensitive test of liver synthetic function in the absence of vita min K de \201 ciency. Prolongation of the PT is predictive of mortality in both acute and chronic liver failure. Reduced factor V level is a poor prognostic marker in non-paraceta- mol acute liver failure. critically ill patients with septic shock or following liver transplantation, but is not wi dely available. Indocyanine green clearance Indocyanine green (ICG) is an infrared-absorbing, iodine- conta ining dye that is excreted unchanged in bile. Plasma levels can be measured non-invasively by transcutaneous infrared spectrophotometry. The rate of ICG clearance can be expressed as blood clearance or plasma disappear- ance rate. Normal values are >700ml/min/m2 and >18%/ min. ICG clearance is dependent upon liver perfusion, hepatocellular function and biliary e xcretion. Low ICG clearance predicts poor survival in cirrhotic patients listed for liver t ransplantation, dysfunction in the graft and worse outcome after liver resection. Reduced I CG clearance is an independent risk factor for mortality in critically ill patients without pre-existing liver disease with septic shock or acute respiratory distress. Ammonia Ammonia is produced throughout the body as the nitrog- enous waste product of amino acid catabolism. The liver detoxi \201 es ammonia to urea via the urea cycle prior to ren al excretion. Ammonia levels rise as a consequence of hepatoportal shunting and may contrib ute to hepatic encephalopathy. Ammonia levels also rise in acute liver fail- ure, Reye synd rome and rare inborn errors of metabolism. Lactate Lactic acid is produced by peripheral tissues, particularly skeletal muscle, brain and red cells as a byproduct of glu- cose metabolism, and metabolized by the liver and kidn ey. Blood lactate levels rise as a consequence of mitochondrial dysfunction secondary to ti ssue hypoxia or sepsis, or due to reduced hepatic perfusion or function. Lactic acidosis in the presence of tissue hypoxia is termed type A, whilst lac- tic acidosis secondary to red uced hepatic clearance is termed type B. Common causes of hyperlactataemia are summarized i n Table 21.5.4. Hyperlactataemia is a poor prognostic sign in acute paracetamol-induced liv er failure. Lactic acidosis is a common feature of critical illness in acute on chronic liv er failure. Monoethylglycinxylidide (MEG-X) test Lidocaine is metabolized to MEG-X via the cytochrome P 450 system. MEG-X is assayed immediately before and 15min after an IV dose of lidocaine (1m g/kg). The MEG-X test therefore measures liver blood \202 ow and hepatocellu- lar functio n. Low rates of conversion of lidocaine to MEG-X are predictive of poor outcome in stable p atients with cirrhosis, cirrhotic patients undergoing liver resection and critically ill pa tients with cirrhosis on the ITU. Measurement of MEG-X requires complex laboratory analysis , so it is not suitable as a bedside test. Accuracy is reduced by concurrent medication tha t induces or sup- presses cytochrome P450. Dynamic tests of liver function Dynamic LFTs assess the ability of the liver to metabolize or eliminate substrates over a short period of time. Dynamic liver function testing is supe rior to static tests (e.g. bilirubin, PT) in the assessment of liver function in This page intentionally left blank 359 Chapter 22 Neurological disorders Chapter Contents Agitation and confusion 360 Status epilepticus 362 Meningitis 364 Intracer ebral hemorrhage 366 Subarachnoid hemorrhage 368 Ischaemic stroke 370 Guillain \200\223Barr e syndrome 372 Myasthenia gravis 374 ICU neuromuscular disorders 376 Tetanus 378 Botulism 3 80 Neurorehabilitation 382 Hyperthermias 384 360 R BOURNE & M BORTHWICK Agitation and confusion Agitation and confusion are common features in critical ill- ness. Agitation is a symptom o r sign of numerous acute and chronic disease states that include pain, anxiety and delir- i um. Agitation is present in around half of ICU patients, with 15% experiencing severe agita tion. Confusion may also be chronic or acute and arise from an overlapping set of path- olo gical processes that includes hypoxia, hypotension, hypoglycaemia and dementia. It is possi ble to be agitated and not confused, and vise versa. Recognition and treat- ment of the und erlying condition is of utmost importance, rather than treating the symptoms alone. Acute c onfusional states are frequently the result of delirium. Delirium is de \201 ned as an acu te change in mental status with a \202 uctuating course, characterized by inattention and disorganized thinking. It is acute cerebral insuf \201 ciency and should be considered as an organ failure (i.e. brain failure). Three subtypes of delirium exist. 1 Hyperactive (ag itated, paranoid) 2 Hypoactive (inattentive, stuporous, withdrawn) 3 Mixed ( \202 uctuates , hyperactive \200\223hypoactive) The incidence of delirium is reported to be between 15 an d 80% in critical care patients. The pure hyperactive form only accounts for 10% of deliri um cases, with the mixed form accounting for a further 45% of cases. The hypoactive form ca n be missed completely or misdiagnosed as depression. The presence of delirium and/or agita tion increases the duration of mechanical ventilation and intensive care LOS. It is also as sociated with higher rates of adverse events, including a 3-fold increase in mortality. The degree of sedative exposure, in particular to benzodi- azepines, is predictive of delirium occurrence Analgesia evaluation Often non-speci \201 c physiological parameters are utilized to guide analgesia, although behavioral aspects are more reliable. Systematic evaluation of pain an d agitation using a behavioral pain score decreases the incidence of pain and agitation. Sleep monitoring Direct nurse assessment of nocturnal sleep time over- estimates sleep quan tity but provides a useful trend marker. Patient report allows sleep quality to be compared with the patient \200\231s own baseline, but a degree of caution is req uired as memory re call can be adversely affected by sedatives, delirium and sleep disturbance itself. Prevention of delirium Multi-factorial intervention programs highlight the effectiveness of preventative strategies in elderly patients, although there is no speci \201 c evidence t hat these work in critically ill patients. Non-pharmacological Non-pharmacological measures essentially add up to good standards of ba sic nursing and medical care. \200 Remove potential organic drivers, e.g. identify and treat hypoxia, infection, pain, etc. Pr ovide support and orientation, e.g. named nurse, TV/ radio, clock, calendar and daily sched ule. Provide an unambiguous environment, e.g. allow clear day \200\223night and activity \200\223sleep cycles. Maintain competence, e.g. ensure patient has glasses, hearing aid, pa rticipates in range of motion exercises. Pharmacological Many drugs contribute to the incidence and severity of delirium. Drugs with antimuscarinic and/or dopaminergic activity are particularly deliriogenic. Changes in bloo d \200\223 brain barrier (BBB) permeability as a result of critical ill- ness and changes i n pharmacodynamics/pharmacokinetics due to multi-organ failure also increase the risk of de velop- ing delirium. Classes of drugs that are particularly culpable include: \200 Detection of delirium Both the level and degree of clarity of a patient \200\231s con- scio usness require assessment. Consciousness level is judged using a subjective sedation \200 \223agitation scale, but a speci \201 c delirium screening tool must also be used to asses s clarity. Agitation can commonly be the result of suboptimal analgesia, and thus pain must be thoroughly assessed. Sleep disturbances are associated with delirium, although it is un known whether this is a cause or effect. Sleep distur- bance may be an early marker for the development of delirium. Antimuscarinic drugs \200\224through overt or covert activity, e.g. hyoscine, amitriptyline , ranitidine, prednisolone. Dopaminergic drugs, e.g. levodopa. GABAminergic drugs, e.g. ben zodiazepines. Drugs that suppress rapid eye movement (REM) sleep with the risk of REM rebou nd upon abrupt discontinua- tion, e.g. opioids, benzodiazepines, tricyclic antidepres- sant s. \200 \200 Sedation \200\223agitation monitoring The use of sedation \200\223agitation scales to titra te doses of sedative drug infusions reduces the quantity of continuous sedatives delivered, the duration of mechanical ventila- tion and intensive care LOS. Numerous validated scorin g systems are available, including the Richmond Agitation- Sedation Scale (RASS); Sedation Agitation Scale (SAS); and the Motor Activity Assessment Scale (MASS). Sedation holds are b ene \201 cial in appropriate patients and reduce patient sedative exposure as well as LOS. Treatment of delirium When preventative measures fail and identi \201 ed organic drivers h ave been or are in the process of being corrected, speci \201 c delirium treatment should be commenced and administered regularly. Hyperactive/mixed delirium Haloperidol Haloperidol is currently the agent of choice, albeit on lim- ited evidence. The initial dose is based on the patient \200\231s degree of agitat ion, age and hepatic function. Due to the \202 uctuating nature of the symptoms, it must be adminis- tered regularly during the period of delirium. The dose is reduced gradually as the patient stabilizes. Delirium screening Delirium screening tools have been developed for use in critical care pa tients, including the Confusion Assessment Method-Intensive Care Unit (CAM-ICU), Intensive Care Delirium Screening Checklist (ICDSC) and Delirium Detection Score (DDS). These do not all examine the same aspects of delirium, and this may explain the variabil- ity in deliriu m incidence when using different tools. 361 CHAPTER 22.1 Agitation and confusion Phenothiazines Phenothiazines such as chlorpromazine are not recom- mended. Although probab ly of similar ef \201 cacy to haloperidol, they posses a less favorable side effect pro \201 le due to increased antimuscarinic and -blocking activity. Atypical antipsychotics E vidence of ef \201 cacy in the critically ill is limited; however, olanzapine, risperidone and quetiapine probably have simi- lar ef \201 cacy to haloperidol and offer an alternati ve where side effects occur, or in Parkinsonism. Olanzapine is the only atypical agent with an immediate release parenteral formulation suitable for acute control of symptoms. Treatment of withdrawal syndromes Withdrawal reactions should be considered and antici- pat ed for medications introduced in the current admission as well as from the patient \200\231 s usual chronic medication. \200 Benzodiazepines. Adopt a withdrawal regimen over days to weeks in dependent patients. Opioi ds. Withdraw opioids slowly in dependent patients. Use adjunctive opioid-sparing analgesia when possible, e.g. paracetamol, gabapentin. Clonidine may reduce some withdrawal symptoms. Antidepressants. Restart medication as soon as possible, using the IV, buccal or rectal ro utes if necessary. Treat symptomatically if no alternative route. Alcohol. Replace thiamine . Benzodiazepines should be used in a tapering regimen. Adjunctive haloperidol may be neede d for treatment of hallucinations. Nicotine. Consider nicotine replacement therapy (NRT) or clonidine. The safety of NRT in the critically ill has been questioned recently. Recreatio nal drugs. Clonidine may be useful in the mixed picture of recreational drugs with or witho ut adjunctive benzodiazepines. Benzodiazepines Benzodiazepines may predispose to, or aggravate delirium when used outside of the treatment of speci \201 c withdrawal deliria (e.g. alcohol). They should generally be avoided and restricted to irregular administration for control of danger- ous psychomoto r activity in severely disturbed patients. Short-acting agents such as midazolam can be use d in these circumstances while awaiting the full effects of other inter- ventions. a2 Agoni sts There is growing interest in the use of agents such as clonidine and dexmedetomidine fo r treatment of delirium. Although some reports suggest that A2 agonists may be useful in th e treatment of hyperactive delirium, there are no supporting peer-reviewed publications. Further reading Brook AD, Ahrens TS, Schaiff RR, et al. Effect of a nursing- implemented se dation protocol on the duration of mechanical ventilation. Crit Care Med 1999; 27: 2609 \200\22315. Brown TM. Drug-induced delirium. Semin Clin Neuropsychiatry 2000; 5: 113 \200\22324. Hypoactive delirium Hypoactive delirium is more dif \201 cult to treat and is associ- ated with a worse outcome. Carson SS, Kress JP, Rodgers JE, et al. A randomized trial of intermit- tent lorazepam vers us propofol with daily interruption in mechan- ically ventilated patients. Crit Care Med 20 06; 34: 1326 \200\22332. Ely EW, Shintani A, truman B, et al. Delirium as a predictor of mortality in mechanically v entilated patients in the intensive care unit. JAMA 2004; 291: 1753 \200\22362. Antipsychotics Haloperidol or atypical antipsychotics in low doses may be of value. Jaber S, Chanques G, Altairac C, et al. A prospective study of agitation in a medical-surgi cal ICU: Incidence, risk factors, and outcomes. Chest 2005; 128: 2749 \200\22357. Stimulants Methylphenidate was reported to bene \201 t cancer patients with hypoactive del irium in a small trial. Lin SM, Liu CY, Wang CH, et al. The impact of delirium on the survival of mechanically vent ilated patients. Crit Care Med 2004; 32: 2254 \200\2239. Night sedation Benzodiazepines and other GABA agonists are not recom- mended in delirious p atients. Lundstrom M, Edlund A, Karlsson S, et al. A multifactorial interven- tion program reduces t he duration of delirium, length of hospitalization, and mortality in delirious patients. J Am Geriatr Soc 2005; 53: 622 \200\2238. Sedating antidepressants Trazodone and mirtazapine have advantages over other sedating anti depressants such as amitriptyline, through reduced antimuscarinic activity and reduced adve rse effects on sleep architecture. Pandharipande P, Shintani A, et al. Lorazepam is an independent risk factor for transitioni ng to delirium in intensive care unit patients. Anesthesiology 2006; 104: 21 \200\2236. Woods JC, Mion LC, et al. Severe agitation among ventilated medi- cal intensive care unit p atients: frequency, characteristics and outcomes. Intensive Care Med 2004; 30: 1066 \200 \22372. Haloperidol IV haloperidol may be useful in patients unable to utilize enteral routes. www.icudelirium.org www.ics.ac.uk Standards: UKCPA Delirium document 362 J ADCOCK Status epilepticus bene \201 t after 2 bolus doses. Should be used in preference to other benzodiazepines if available. OR IV Diazepam 10 \200\22320mg at a rate of 2 \200\2235mg/min (risk of apnoea wi th faster injection). Do not repeat more than twice, or to a total of >40mg because of risk s of hypoten- sion or respiratory depression. Status epilepticus is de \201 ned as seizure lasting >30min, or as seizures that recur ove r 30min without the patient regain- ing consciousness between seizures. Any seizure type ca n evolve into status epilepticus, but this chapter focuses on tonic \200\223clonic status e pilepticus, which is a neurological emergency. Annual incidence is 18 \200\22328 cases per 100 000, and it occurs most frequently in children, patients with learning difficulties and patients with structural brain lesions (especially in the frontal lobes). It can develop i n patients with established epilepsy (particularly in the context of drug withdrawal) or in de novo patients. Up to 5% of adults attending specialist epilepsy clinics experience one episode of status during the course of the epilepsy. Causes in de novo patients include tra uma, cerebrovascular disease, tumors, encephalitis, alcohol and drug with- drawal, and toxi c disturbances. Status accounts for up to 3.5% of admissions to neurological intensive care , and 0.13% of patients attending a university casualty depart- ment. Mortality is up to 20 %, most often due to the under- lying condition rather than the status itself. The longer t he duration of the status, the greater the morbidity. Treatment of status involves terminat ion of the seizures, preventing recurrence once status controlled, manage- ment of the comp lications, and treatment of the underlying precipitant. Complications of convulsive status epilepticus relate to either the cerebral and metabolic consequences of prolonged convulsio ns or the effects of treatment. They include tachyarrhythmias, pulmonary oedema, hyperther- mia, rhabdomyolysis, aspiration pneumonia, myocardial ischaemia, pulmonary emboli, ARDS, c erebral hypoxia, electrolyte disturbance, metabolic acidosis and ultimately multi-organ fai lure. Drug treatments may cause respiratory depression, cardiac arrhythmias, hypotension an d gastric paresis. Fluid resuscitation and inotropic support may be required. Therefore, ra pid seizure control is mandatory. Second-line medication (10 \200\22360min of presentation) One of these should be instituted without delay if there is any suggestion that the status will not be halted by initial ben zodiazepine. The choice depends on availability and whether the patient is already taking o ne of these medica- tions on a regular basis. IV fosphenytoin sodium (Pro-epanutin): fosphe nytoin can be infused at 3 times the speed of phenytoin and is signi \201 - cantly better tolerated at infusion sites. It should be given in preference to phenytoin if available. As with phenytoin, it can cause hypotension and arrhythmias. Dose: 15mg PE/kg at a rate of 10 0mg PE/min (PE = pheny- toin equivalent units) OR IV phenytoin. Disadvantages: hypotension, arrhythmias, administration must be slow, effective blood levels not obtained until 20 \200\22330min after infusion commenced. Contraindications: AV block. Ampoules contain pheny toin 250mg in 5 ml, which should be diluted in normal saline to a concentration of no more than 10mg/ml. Check there is no precipitate. The infusion should be completed within 1h of mixing. Dose: 15 \200\22318mg/kg at a rate not exceeding 50mg/min (<30mg in the elderly) be cause of the risk of fatal arrhythmia AND/OR If the status persists then give phenobarbiton e. IV phenobarbitone: may cause respiratory depression and hypotension. Contraindications: acute intermittent porphyria. Ampoules contain 200mg/ml. Must be diluted with water for inj ection to a concentration of not more than 20mg/ml. Dose: 10mg/kg to a maximum of 1000mg at a rate of 100mg/min, followed by 1 \200\2234mg/kg/day Some centers prefer to use a 3rd non -anesthetic before induction of coma. IV sodium valproate 25 \200\22345mg/kg bolus (up to 5 00mg/min), particularly if the patient is in non-convulsant status, where anesthetic agents are preferably avoided. Treatment of convulsive status epilepticus General measures \200 \200 Secure the airway + oxygen intubate Set up 2 IV lines for administration of \202 uids and drugs Benzodiazepines should be given through a separate IV line Set up continuous ECG and BP monitoring Send blood for gasses, FBC, electrolytes, glucose, calcium, LFTs, anticon vulsant blood levels Ensure that routine antiepileptic drug (AED) doses are maintained if a lready on medication IV glucose and/or thiamine if appropriate Treat complications Commence long-term anticonvulsant therapy Be vigilant that the patient is not in pseudostatus epile pticus \200 \200 \200 \200 Third-line treatment for refractory status (30 \200\22390min from presentation) This should be instituted if the convulsion has continued for >60min. The patient should be intubated and ventilated (if not already undertaken). Ideally continuous EEG moni- toring should be u ndertaken. Thiopentone 100 \200\223250mg bolus, then 50mg bolus every 3min until burst supp ression on EEG. Maintenance 3 \200\2235mg/kg/h. OR Propofol 2mg/kg bolus, then repeat bolus if necessary. Maintenance 5 \200\22310mg/kg/h. Immediate \201 rst-line medication (within 10min of presentation) IV Lorazepam 0.07mg/kg body weight to a maximum of 4mg, which can be repeated. Ampoules (Ativan injection) con- ta in 4mg in 1ml. Advantages: long duration of action, less likely to cause sudden hypotension or respiratory arrest because of lack of CNS accumulation after bolus dose. Disadvantages: rapid tolerance, therefore of no further 363 CHAPTER 22.2 Status epilepticus Some units also use midazolam infusions before undertak- ing anesthetic coma using the foll owing regime: 0.2mg/kg bolus, followed by a continuous infusion of 0.1 \200\2230.4mg/kg/h. No systematic RCT of status epilepticus has yet been pub- lished to compare different anest hetic agents directly in this circumstance. Therefore, the choice of agent depends on the p reference of the intensive care physician. to ICUs with a diagnosis of status epilepticus actually have non-epileptic attack disorder, or \200\230pseudostatus \200\231. The diag- nosis should be suspected if a patient has ha d multiple presentations with suspected status, particularly if there is also a history of self-harming behavior, deliberate overdose or frequent presentations with medically unexpla ined symp- toms. Such patients are often younger, female, have lower CK levels and receive signi \201 cantly higher doses of benzodi- azepine, leading to respiratory failure. Clinic al features of the non-epileptic episodes include pelvic thrusting, poorly controlled thras hing, back arching, eyes held tightly closed and head rolling. Serum prolactin levels are n ot always helpful, as prolactin levels normalize with prolonged true seizure activity. Icta l EEG and specialized knowledge of sei- zure semiology usually can differentiate the condit ions, but these are often not available after hours in the emergency situation. These patie nts are at risk of iatrogenic complica- tions from aggressive treatment for suspected true convul- sive status. Other drugs Some patients remain highly resistant to treatment despite aggressive anestheti c coma. There are some case reports of such patients \201 nally responding to topiramate given enterally in doses of 300 \200\2231600mg, or enteral levetiracetam 500 \200\2233000mg /day (which is also now available in some countries in IV form). Long-term anticonvulsant t herapy must be given in con- junction with emergency treatment. The choice of drug depends on previous therapy, the epilepsy type and the clinical setting. Maintenance doses can be g iven orally via an NG tube and can be guided by serum level monitoring. Prognosis The outcome after an episode of status epilepticus is poor, with mortality rates being as high as 10 \200\22320%. Predictors of mortality include old age, the underlying et iology of the status, the lack of prior history of epilepsy, the requirement for barbiturat e coma and the level of consciousness at presentation. There is also a risk of cognitive de cline and late epilepsy. Speci \201 c cerebral monitoring In prolonged status, and in comatose ventilated patients, motor activity may not be visible. Continuous EEG moni- toring should be undertaken if pos sible, or at least daily EEG if available. This will monitor ongoing electrical seizure act ivity or burst suppression, which provides a target for the titration of anesthetic therapy . Dosing is commonly set at a level that will produce burst suppression with interburst int ervals of between 2 and 30s. Once the patient has been free of seizures for 12 \200\22324h and provided that there are adequate blood levels of concomitant AED medication, then the a nesthetic should be slowly tapered. ICP monitoring is sometimes required in the presence of persisting, severe or progressive elevated ICP. The need for this is usually determined by the underlying cause rather than the status itself. IPPV, high dose corticosteroid therapy (dexamethasone 4mg every 6h) or mannitol infusion may be used if there is a danger of tent orial coning. Neurosurgical decompression or speci \201 c resective surgery is occasionall y required. Support groups The National Society for Epilepsy: www.nse.org.uk Epilepsy Foundation of Ame rica: www.epilepsyfound ation.org Further reading Holtkamp M. The anesthetic and intensive care of status epilepticus. Curr Opin Neurol. 2007; 20: 188 \200\22393. Holtkamp M, Othman J, Buchheim K, et al. Diagnosis of psychogenic nonepileptic status epile pticus in the emergency setting. Neurology 2006; 66: 1727 \200\2239. Howard RS, Kullmann DM, Hirsch NP. Admission to neurological intensive care: who, when, and why? J Neurol Neurosurg Psychiatry. 2003; 74 Suppl 3: iii2 \200\2239. Malignant status epilepticus There are some patients who remain in status lasting weeks to months. Such patients are often young, female, and present de novo without any clear precip itant of focal underlying brain lesion. This condition is known as \200\230cryp- togenic d e novo refractory status epilepticus \200\231. \200\230new-onset refractory status epilept icus \200\231 or \200\230malignant status epilepti- cus \200\231. The presumed underlying cause is often thought to be a form of encephalitis, as the CSF in such patients often cont ains mononuclear cells. Howell SJ, Owen L, Chadwick DW. Pseudostatus epilepticus. Q J Med 1989; 71): 507 \200\22319. Rossetti AO, Logroscino G, Brom \201 eld EB. A clinical score for the prognosis of status epilepticus in adults. Neurology 2006; 66: 1736 \200\2238. Shorvon S. The management of status epilepticus. J Neurol Neurosurg Psychiatry 2001; 70 (Suppl II): ii22 \200\2237. Shorvon S, Dreifuss F, Fish D, et al. The treatment of epilepsy. Oxford: Blackwell Science Ltd, 1996. Walker MC. Status epilepticus on the intensive care unit. J Neurol 2003; 250: 401 \200\2236. Walker M. Status epilepticus: an evidence based guide. BMJ 2005; Differential diagnosis: psychogenic status epilepticus It must be remembered that not all t hat shakes is epilepsy. It has been estimated that up to 50% of patients admitted 331): 673 \200\2237. 364 P GILLIAN Meningitis De \201 nition Meningitis is the term given to an in \202 ammation of the meninges, the p rotective layers surrounding the brain and spinal cord. The causes of this in \202 ammatio n are multiple, and include infection, trauma, neoplastic, autoimmune and drug causes. The subsequent in \202 ammatory response may cause damage to the adjacent structures and hence cause neurological damage and the potential for death, and as such requires prompt investi gation and treatment. In most cases, meningitis is due to an infective etiology, which can be bacterial, viral or fungal. Viral meningitis is the most common form and usually follows a benign course. However, bacterial meningitis is a serious disease that is associated wit h signi \201 cant morbidity and mortality, and remains so despite attempts to reduce its e ffect. Investigations Investigations should be commenced concurrently with empiric antibacterial t reatment if a diagnosis of meningitis is suspected. These investigations include: \200 FB C including differential \200 U&E \200 Blood glucose \200 LFTs \200 CRP assay \200 Clotting studies \200 ABG with serum lactate \200 Blood cultures if pyrexia present \200 Throat swab \200 EDTA blood sample for PCR \200 Urine for pneumococcal antigen \200 Blood/ skin scraping of rash for urgent Gram stain \200 ECG \200 Consider lunbar puncture (LP) \200 Consider CT Epidemiology and incidence The incidence of bacterial meningitis is 3/100 000 (rates of Hae mophilus and meningococcal type C infections are being reduced by ongoing vaccination campa igns). Causes The most likely bacterial pathogens as considered by patient age. De \201 nitive diagnosis may require CSF identi \201 cation of a pathogen via LP. If ther e are no clinical contraindications to LP, a CT scan may not be required. A normal CT scan does not exclude raised ICP. However, LP is contraindicated in the presence of raised ICP, due to the potential to cause brain herniation. LP is also rela- tively contraindicated in meningococcal septicaemia. Age group Causes Neonates Group B streptococci, Escherichia coli, Listeria monocytogenes Infants Neisseria meningitidis, Haemophilus in \202 uenzae, Streptococcus pneumoniae Lumbar puncture \201 ndings Low High High, often >300/mm Acute bacterial meningitis Children N. meningitidis, S. pneumoniae Adults S. pneumoniae, N. meningitidis, mycobacteria, cryptococci Normal Normal or high Mononuclear, < 300/mm Acute viral meningitis Low High Pleocytosis, mixed <300/mm Tuberculous meningitis Symptoms and signs Variable presentation usually accompanied by corryzal symptoms in the pr odromal phase. This is often followed by rapid clinical deterioration. The triad of symptom s neck stiffness, altered mental state and fever are classical; however, these are only fou nd in 40% cases. The most common symptoms are headache, neck stiffness and photophobia. Ot hers include fever, phonophobia, diminished consciousness and seizures. Young infants may a lso present with fontanelle signs indicative of the disease process. Other signs include th e presence of a petechial, rapidly spreading rash often affecting the trunk and lower extre m- ities which is indicative of N. meningitides (meningococcal) meningitis. Low High < 300/mm Fungal meningitis Low High Usually mononuclear Malignant meningitis Normal Normal or high Erythrocytes Subarachnoid hemorrhage Many new diagnostic clinical tests are currently being evaluated in an attempt to distingui sh bacterial meningitis from other causes of the disease rapidly. The Bacterial Meningitis Score can distinguish bacterial from viral menin- gitis (the weighted predictive points inc lude a positive Gram stain, CSF protein >80mg/dl, peripheral absolute neutrophil count (ANC ) >10 000 cells/mm3, seizure at or before presentation and CSF ANC >1000 cells/mm3). Other tests include WBC, CRP and many CSF in \202 amma- tory markers No de \201 nitive test i s currently available. Eponymous signs \200 Kernig \200\231s sign: pain elicited on passive \202 exion of knees which represents nuch al sensitivity. Brudzinski \200\231s sign: neck \202 exion causing lower limb \202 exio n, especially in pediatric cases. Management The initial management of bacterial meningitis is to provide systematic support until an appropriate antibiotic regime has been implemented. However, in the initial phase of illness, bacterial and viral meningitis share many common features. In most circumstance s, a broad-spectrum Whilst commonly performed, many authors question the validity of these tests. 365 CHAPTER 22.3 Meningitis antibiotic regime to combat the suspected bacterial menin- gitis is commenced, based on epi demiological analysis of likely pathogens. (see above) analgesia. In some cases, including the immunocompro- mised, antiviral agents may be consid ered. Fungal meningitis Rare in the immunocompetent. Cryptococcus neoformans is the most common p athogen causing AIDS-related fungal meningitis. Treatment involves a prolonged course of an tifungals. Treatment Bacterial meningitis is a medical emergency and has a high mortality rate if untr eated. Following initial recognition, prompt senior intervention is required. Post-neurosurgical meningitis: The most common bacterial pathogens are staphylococci and Gr am-negative bacilli, especially in the presence of prosthetic material. Cephalosporins rema in ef \201 cacious treatment, dependent on local microbiological advice. If P. aeruginosa is isolated or suspected, Ceftazidime is pre- ferred. In those patients with resistant path ogens, vancomycin or chloramphenicol may be considered. Antimicrobial \200 Cephalosporins (2g Ceftriaxone or Cefotaxime) remain the \201 rst-line antimicrobial agen ts. Ampicillin 2g IV qds may be added in patients in whom Listeria monocytogenes is suspect ed (age <3 or >55yrs). Vancomycin may be required if pneumococcal penicil- lin resistanc e is considered likely. This may be changed on microbiological advice, once a pathogen has been identi \201 ed. Pediatric meningitis The management of meningococcal disease in pediatric patients requires early senior specialist pediatric and/or intensive care clinicians. A complete overview of the initial management is described by Pollard et al. Adjunctive Adjunctive treatment of bacterial meningitis with steroids have been proven to r educe its mortality and morbidity, including the rates of severe hearing loss and other neu ro- logical sequelae Some advocate the use of anticonvulsants and empirical antiviral thera pies. Public health considerations \200 Bacterial meningitis is a Noti \201 able Illness. Ensure that CCDC have been informed of l ikely/proven case to ensure prophylaxis can be considered for contacts. Isolation of the pa tient for the \201 rst 24h on admission is considered bene \201 cial. Notify microbiolog ical staff. Organ support Organ support via appropriate respiratory and cardiovas- cular treatment is m ost likely to be performed in a critical care environment. This may include: \200 Volume resuscitation isotropic or vasopressor sup- port in the presence of a systemic in flammatory response syndrome or shock Consider intubation and ventilation in refractory hyp oxia Consider tight glycaemia control, low dose corticoster- oid therapy and APC Correct el ectrolyte disturbances If signs of raised ICP treat with appropriate medical man- agement i ncluding ensuring control of PaCO2, 30 bed- head elevation, normothermia and the preventi on of seizures. Assess and treat sequelae. Further reading Beckham J, Tyler K. Initial management of acute bacterial meningitis in adu lts: summary of IDSA guidelines. Rev Neurol Dis 2006; 3: 57 \200\22360. \200 Hasbun R, Abrahams J, Jekel J, et al. Computed tomography of the head before lumbar punctur e in adults with suspected meningitis. N Engl J Med 2001; 345: 1727 \200\22333. \200 Pollard AJ, Britto J, Nadel S, et al. Emergency management of menin- gococcal disease in children. Arch Dis Child 1999; 80: 290 \200\2236. Nigrovic L, Kuppermann N, Malley R. Development and validation of a multivariable predictiv e model to distinguish bacterial from aseptic meningitis in children in the post-haemophilu s in \202 uenzae era. Pediatrics 2002; 110: 712 \200\2239. Prognosis Prognostic indicators of disease severity relate to the aeti- ology (bacterial, v iral, etc.) and the clinical \201 ndings, along with the development of complications. Ho lub et al. have proven the ef \201 cacy of CSF cortical levels as having prognostic predic tive value in bacterial meningitis. Provan D, Krentz A. Oxford handbook of clinical and laboratory investigation. Oxford: Oxford University Press. 2005. Thomas KE, Hasbun R, Jekel J, et al. The diagnostic accuracy of Kernig \200\231s sign, Brud zinski \200\231s sign, and nuchal rigidity in adults with suspected meningitis. Clin Infect Dis 2002; 35: 46 \200\22352. van de Beek D, de Gans J, McIntyre P, et al. Corticosteroids for acute bacterial meningitis . Cochrane Database Syst Rev 2007; (1): CD004405. Viral meningitis Viral meningitis is usually a self-limiting condition which responds to su pportive treatment, \202 uids, antipyretics and 366 M SMITH Intracerebral hemorrhage Investigations Cranial CT scan \200 \200 Intracerebral hemorrhage (ICH) is an acute spontaneous extravasation of blood into the brai n parenchyma. Urgent CT will con \201 rm the diagnosis of ICH The cause of the ICH may be suggested by t he pattern of bleeding The volume of the haematoma can be estimated Con \201 rmation of ex travasation of contrast into the hae- matoma predicts haematoma expansion Epidemiology \200 ICH accounts for 10 \200\22330% of all strokes but is one of the major causes of stroke-rel ated death and disability. >85% of cases of ICH occur as a primary event following spontane ous hemorrhage arising from rupture of small arteries and arterioles. The majority of prima ry ICH is associated with hyper- tension (60 \200\22370% of cases) or amyloid angiopathy (1 5% of cases). Around half of primary ICH occurs in the basal ganglia, one-third in the cere bral hemispheres and one-sixth in the brainstem or cerebellum. Secondary ICH is hemorrhage arising as a result of trauma, rupture of an intracranial aneurysm, an AV malformation or a coagulopathy. \200 MRI scan \200 \200 MRI is as sensitive as CT for acute detection of ICH Generally used as a follow-up study to identify AV mal- formation, amyloid angiopathy or associated neoplasm. Cerebral angiography \200 Angiography is useful for con \201 rming vascular causes of ICH such as AV malformation, d ural AV \201 stula, cortical vein thrombosis or vasculitis Angiography should always be c onsidered in young patients with no obvious risk factors for ICH. Incidence \200 \200 12 \200\22315 cases per 100 000 of the population More common in males, the elderly and in those of Asian and African ethnicity Incidence of ICH is signi \201 cantly increased in pa tients receiving antiplatelet or anticoagulation therapy. Management ICH should be treated as a medical emergency since delays in treatment are assoc iated with worse outcome \200\224the concept of \200\230time is brain \200\231 has recentl y been described Acute treatment includes airway management and control of blood pressure a nd ICP. Airway management is a prior- ity when conscious level is impaired in order to prot ect the airway and facilitate mechanical ventilation to minimize secondary brain injury fro m hypoxaemia and hypercarbia. Mortality after ICH is reduced in patients cared for in speci alist neurointensive care units.