Raised intracranial pressure Clinical features \200 \200 \200 \200 \200 \200 \200 Headache, vomiting, dizziness, visual disturbance. Seizures, focal neurology, papilloedema. Increasing blood pressure, bradycardia (late responses). Agitation, increasing drowsiness, coma. Slow deep breaths, Cheyne \200\223Stokes breathing, apnoea. Ipsilateral progressing to bilateral pupillary dilatation. Decorticate progressing to decerebrate posturing. Diagnosis \200 \200 CT scan or MRI. Intracranial pressure (ICP) measurement >20mmHg. Lumbar puncture should be avoided because of the risk of coning. Neither CT scan nor absenc e of papilloedema will exclude a raised ICP. Management 1. Bed rest, 20 \200\22330* head-up tilt, sedation, quiet environment, minimal s uction and noise. Sedation and B-blockade are often necessary to overcome a hyperadrenergic state, but sedative-induced hypotension should be avoided. The tape tethering the endotrac heal tube in place should not occlude jugular venous drainage. 2. Ventilate if GCS \211 8, airway unprotected, or excessively agitated. 3. Maintain PaCO2 at 4 \200\2234.5kPa and avoid rapid rises. CSF bicarbonate levels re-equilibrate within 4 \200\2236h, negating any bene \201 t from hyperventilation. 4. If available and not contra indicated, monitor ICP. Aim to maintain ICP <20mmHg and cerebral perfusion pressure (= MAP \200\223 ICP) >70mmHg. Vasopressor therapy may be needed. Do not treat systemic hyperten- sion unless very high (e.g. systolic >220 \200\223230mmHg). 5. Other monitoring techniques, e.g. jugular bulb venous saturation (SjO2) and lactate, may be useful though they do not detect regional ischaemia. 6. Give mannitol 0.5mg/kg IV over 15min. Repeat at 4-hourly intervals depend- ing on cerebral perfusion pressure (CPP) measur ements and/or clinical signs of deterioration. Stop when plasma osmolality reaches 310 \200 \223320mOsm/kg. 7. Avoid severe alkalosis as cerebral vascular resistance rises and cerebra l ischaemia increases. 8. Consider speci \201 c treatment, e.g. for meningo-encephalitis, malaria, he- patic ence phalopathy, surgery. Some neurosurgeons will decompress the cranium for generalized oedema by removing a skull \202 ap. Seek local advice. Dexamethasone 4 \200\22316mg qds IV is be ne \201 cial for oedema sur- rounding a tumor or abscess and for herpes simplex encephalit is. Acute deterioration/risk of imminent coning 1. Mechanically ventilate to PaCO2 3.0 \200\223 3.5kPa for 10 \200\22320min. 2. Give mannitol 0.5g/kg IV over 15min. Repeat 4-hourly as nec essary and stop when plasma osmolality >310 \200\223320mOsm/kg. Consider therapeu- tic hypo thermia. 3. If no response in ICP, CPP and/or clinical features, give thiopental (successful in 50% of resistant cases). 4. Consider repeat CT scan and refer for urgent surgery if a surgically- amenable space-occupying lesion is diagnosed. RAISED INTRACRANIAL PRESSURE 455 Causes of raised intracranial pressure \200 \200 Space-occupying lesion (e.g. neoplasm, blood clot, abscess). Increased capillary permeabili ty (e.g. trauma, infection, hepatic encephalopathy). Cell death (e.g. hypoxia). Obstruction (e.g. hydrocephalus). \200 See also: Oxygen therapy, p38; Ventilatory support \200\224indications, p44; Therapeutic hy pothermia, p100; Blood pressure monitoring, p164; Intracranial pressure monitoring, p200; J ugular venous bulb saturation, p202; Other neurological monitoring, p206; Neuroprotective a gents, p312; Basic resuscitation, p338; Acute liver failure, p430; Hepatic encephalopathy, p432; Coma, p438; Generalized seizures, p444; Meningitis, p446; Intracranial hemorrhage, p4 48; Subarachnoid hemorrhage, p450; Stroke, p452; Head injury (1), p586; Head injury (2), p5 88; Brain stem death, p652. 456 CHAPTER 27 Neurological disorders Guillain \200\223Barr syndrome \200 \200 \200 An immunologically mediated acute demyelinating polyradiculopathy. Viral infections and imm unisations are common antecedents. It includes a progressive, are \202 exic motor weakness (often symmetrical, ascending, and involving cranial nerves, including facial, bulbar, and extraocular weakness) with progression over a few days to weeks. There are often minor sen sory disturbances (e.g. paraesthesiae). Autonomic dysfunction is not unusual. There is no i ncrease in cell count on CSF examination, but protein levels usually rise progressively (>0 .4g/L). Nerve conduction studies show slow conduction velocities with prolonged F waves. Ot her features include muscle tenderness and back pain. The major contributors to morbidity a nd mortality are respiratory muscle weakness and autonomic dysfunction (hypotension, hypert ension, arrhythmias, ileus, and urinary retention). \200 \200 \200 Differential diagnosis Other causes of acute weakness must be excluded before a diagnosis o f Guillain \200\223Barr syndrome can be made. Speci \201 c treatment \200 Intravenous immunoglobulin (0.4g/kg/d for \201 ve days) or plasma exchange ( \201 ve 50m L/kg exchanges over 8 \200\22313 days) is effective if started within 14 days of onset of s ymptoms. Corticosteroids have not been shown to be bene \201 cial. Supportive treatment Respiratory care Regular chest physiotherapy and spirometry are requir ed. Mechanical ven- tilation is needed if FVC <1L or PaCO2 is raised. An early tracheostomy is useful since mechanical ventilation is likely to continue for several weeks. Patients w ith bulbar involvement or inadequate cough should have a tra- cheostomy even if spontaneous breathing continues. Cardiovascular care Continuous cardiovascular monitoring is required due to the effects of autonomic involvement. Arrhythmias are particularly likely with anaes- thesia (especially w ith suxamethonium). Hypertensive and hypotensive responses are generally exaggerated with v asoactive drugs. Nutritional support Parenteral nutrition will be required in cases where there is ileus. En teral nutrition is preferred if possible, but it should be noted that energy and \202 uid requirements are reduced in Guillain \200\223Barr syndrome. Analgesia Analgesia is required for muscle, abdominal, and back pain. Although NSAIDs may b e useful, opiates are often required. Other support Particular attention is required to pressure areas and deep vein throm- bosis prophylaxis. GUILLAIN \200\223BARR \211 SYNDROME 457 Key papers Plasma Exchange/Sandoglobulin Guillain-Barr Syndrome Trial Group. (1997) Rando mized trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guil lain-Barr syndrome. Lancet 349: 225 \200\22330. van Koningsveld R, for the Dutch GBS study group. (2004) Effect of methylprednisolone when added to standard treatment with intravenous immunoglobulin for Guillain-Barr syndrome: r an- domised trial. Lancet 363: 192 \200\2236. Hughes RA, Swan AV, Rapha l JC, et al. (2007) Immunotherapy for Guillain-Barr syndrome: a systematic review. Brain 130: 2245 \200\22357. See also: Airway maintenance, p40; Endotracheal intubation, p42; Ventilatory support \200 \224indications, p44; Plasma exchange, p114; Pulmonary function tests, p148; ECG monitoring , p162; Blood pressure monitoring, p164; Respiratory failure, p350; Hypotension, p380; Hype rtension, p382; Tachyarrhythmias, p384; Bradyarrhythmias, p386; Acute weakness, p440. 458 CHAPTER 27 Neurological disorders Myasthenia gravis \200 Myasthenia gravis is an autoimmune disease associated with acetylcholine receptor and, rare ly, anti-striated muscle antibodies. It is associated with autoimmune thyroid disease, SLE, and rheumatoid arthritis. Painless weakness with normal tendon re \202 exes, deterioratin g after exertion, and recovering after rest. Weakness deteriorates during stress, infection , or trauma. Younger (<45y), predominantly female patients may have a thymoma which, if res ected, may provide remission. Diagnosis of myasthenia \200 \200 Edrophonium is a short-acting anticholinesterase used in the diagnosis. In myasthenic patie nts with an acute deterioration, the test may distinguish a myasthenic from a cholinergic c risis. In cholinergic crisis, edrophonium may cause further deterioration so atropine and f acilities for urgent intubation and ventilation should be available. To minimize the risk, a test dose of 1mg is administered. After one minute, give an additional 4mg and, if no cha nge is apparent in one minute, give another 5mg. A positive test is judged by improvement o f weakness within 3min compared to no improvement with saline injection. The test may be co mbined with objective assessment of respiratory function by measuring the FVC response or b y assessing the response to repetitive stimulation with an EMG. Maintenance treatment Anticholinesterase drugs provide the mainstay of symptomatic treat- m ent, but corticosteroids, immunosuppressives, and plasma exchange may provide pharmacologic al remission. Anticholinesterases may produce improvement in some muscle groups and choline rgic deterioration in others due to differential sensitivity. Myasthenic crisis \200 \200 Mechanical ventilatory support if FVC <1L or PaCO2 is raised. New myasthenics should be sta rted on corticosteroids 9 azathioprine and pyridostigmine. Plasmapheresis may reduce antibo dy load. Known myasthenics require corticosteroids and increased pyridostigmine or neostigm ine 9 IV immunoglobulin. If the condition deteriorates drug therapy should be stopped; plas ma exchange may be life-saving. Cholinergic crisis \200 \200 Mechanical ventilatory support if FVC <1L or PaCO2 is raised. Cholinergic symptoms (e.g. sw eating, salivation, lacrimation, colic, fasciculation, confusion, ataxia, small pupils, bra dycardia, hypertension, seizures) are usually most severe 2h after the last anticholinester ase. Atropine given prophylactically in the treatment of myasthenia may mask some of the ch olinergic symptoms. If a deterioration fails to respond to edrophonium, all drugs should be stopped and atropine given. Repeat edrophonium test every 2h and reintroduce anticholinest erases when positive. MYASTHENIA GRAVIS 459 Drug dosages Prednisolone 80mg/d orally Azathioprine 2.5mg/kg/d orally Pyridostigmine 60 \200\223180mg 6-hourly orally Neostigmine 1 \200\2232.5mg 2 \200\2234 hourly IV Atropine 1mg 6-hourly IV, repeated every 30min to maximum of 8mg Drugs causing deterioration in myasthenia gravis \200 \200 \200 \200 \200 \200 Aminoglycosides. Streptomycin. Tetracyclines. Local anesthetics. Muscle relaxants. Opiates. See also: Airway maintenance, p40; Endotracheal intubation, p42; Ventilatory support \200 \224indications, p44; Plasma exchange, p114; Pulmonary function tests, p148; ECG monitoring , p162; Blood pres- sure monitoring, p164; Corticosteroids, p328; Respiratory failure, p350 ; Hypertension, p382; Bradyarrhythmias, p386; Acute weakness, p440; Generalized seizures, p 444; Vasculitides, p574. 460 CHAPTER 27 Neurological disorders Critical care neuromuscular disorders Neuromuscular disorders in the critically ill have lo ng been recognized, particularly in those mechanically ventilated. First suspicions are oft en raised when patients fail to wean from mechanical ventilation or limb weakness is noted on stopping sedation. This may be profound and can persist for weeks to months. Occasionall y, it may be permanent. Variable degrees of neuropathy and myopathy are found on EMG, nerve conduc- tion studies, and biopsy. Corticosteroids and prolonged use of paralyzing agents a re implicated, but this remains unproven. Disuse atrophy, catabolic states, and drug therap y (e.g. high-dose corticosteroids, muscle relaxants) are probably responsible for some case s, but do not explain all. A neu- romyopathic component of multi-organ dysfunction syndrome may be relevant. Critical illness neuropathy \200 Neurophysiological studies have demonstrated an acute, idiopathic, axonal degeneration in p atients with \202 accid weakness following a prolonged period of intensive care. Sensatio n may be affected, alone or in combination with motor \201 bres. Nerve conduction velocit ies are normal indicating no demyelination. CSF is normal unlike Guillain \200\223Barr sy ndrome. The neuropathy is self-limiting, but prolongs the recovery phase of critical illnes s. Recovery may take weeks to years. Recovery requires multidisciplinary teamwork for rehab ilitation and management of neuropathic pain. Pyridoxine (100 \200\223150mg daily PO) has b een used in the treatment, but supporting evidence is not strong. \200 Critical illness myopathy \200 Disuse atrophy and drug induced myopathy are common in critically ill patients. Corticoster oid-induced myopathy is less common as the indications for high-dose corticosteroids have b een reduced. Muscle relaxants may have a prolonged effect and may be potentiated by B2 agon ists. They may be associated with structural myopathic changes when used in asthma. Muscle histological studies have demonstrated abnormalities ( \201 bre atrophy, mitochondrial def ects, myopathy, and necrosis) which could not be associated with corticosteroid or muscle r elaxant therapy. Myopathy may cause renal damage via myoglobinuria. Critical illness myopat hy is associated with various forms of muscle degeneration, but is usually self-limiting. R ecovery may take weeks to years. Occasionally, residual de \201 cit remains. Recovery requ ires multidisciplinary teamwork for rehabilitation. CRITICAL CARE NEUROMUSCULAR DISORDERS 461 See also: IPPV \200\224assessment of weaning, p60; Sedatives and tranquilisers, p308; Muscl e relaxants, p310; Acute weakness, p440; Systemic in \202 ammation/multi-organ failure \200\224causes, p556. 462 CHAPTER 27 Neurological disorders Tetanus The clinical syndrome caused by the exotoxin tetanospasmin from the anaerobe, Clost ridium tetani, in contaminated or devitalised wounds. Tetanospasmin ascends intra-axonally in motor and autonomic nerves, blocking the release of inhibitory neurotransmitters. The di sease may be modi \201 ed by previous immunization such that milder or localized symp- tom s may occur with heavier toxin loads. Clinical features \200 Gradual onset of stiffness, dysphagia, muscle pain, hypertonia and rigidity, and muscle spa sm. Laryngospasm often follows dysphagia. Muscle spasm is often provoked by minor disturban ce, e.g. laryngospasm may be provoked by swallowing. Onset of symptoms within \201 ve day s of injury implies a heavy toxin load and severe disease. The disease is self-limiting so treatment is supportive, but may need to continue for several weeks. \200 Management of the wound If a contaminated wound is present, it should be debrided surgicall y after 250IU human tetanus immunoglobulin has been given (in a different site to any tetan us toxoid immunization). Benzylpenicillin 1.2g 6-hourly and met- ronidazole 500mg 8-hourly IV are appropriate antibiotics. Tetanus-prone wounds include: \200 \200 Any wound or burn sustained more than 6h before surgical treatment. Any wound or burn with a signi \201 cant degree of devitalised tissue, puncture-type wounds, contact with soil or manure, or clinical evidence of sepsis. Mild tetanus Patients with mild symptoms, no respiratory distress, and a delayed onset of s ymptoms should be nursed in a quite environment with mild sedation to prevent tetanic spasm s. Severe tetanus \200 Intubate and ventilate since asphyxia may occur due to prolonged respiratory muscle spasm. Sedate with diazepam (PO or IV as necessary). Muscle rigidity is best treated with magnesiu m sulfate 20mmol/h IV or benzodiazepines, with the addition of muscle relaxants if necessar y. Autonomic hyper-reactivity (arrhythmias, hypotension, hypertension, and myocardial ischa emia) is often seen. It is minimized by sedation, anesthesia, and treated by atropine 1 \200\22320mg/h IV, propranolol 10mg 8-hourly IV or NG, and magnesium sulfate 20mmol/h IV. H uman tetanus immunoglobulin 1000 \200\2231500 units IM may shorten the course of the diseas e by removing circulating toxin. Rapid \201 xation of the toxin to tissues limits the use fulness of this approach. \200 TETANUS 463 Tetanus toxoid prophylaxis The disease confers no immunity so patients must be immunized pr ior to hospital discharge. \200 \200 \200 Last dose of tetanus toxoid <5 years Last dose of tetanus toxoid <10 years No previous immu nization No further dose One dose 3 doses See also: Airway maintenance, p40; Endotracheal intubation, p42; Ventilatory support \200 \224indications, p44; Sedatives and tranquilisers, p308; Antimicrobials, p326; Respiratory failure, p350; Hypotension, p380; Hypertension, p382; Tachyarrhythmias, p384; Bradyarrhythm ias, p386. 464 CHAPTER 27 Neurological disorders Botulism An uncommon, lethal disease caused by exotoxins of the anaerobe Clostridium (C.) b otulinum. Botulism is most commonly a foodborne disease, especially associated with canned foods. It may be contracted by wound contamination with aquatic soils or from skin popping (C. novyi or C histolyticum introduced from drug abusers injecting into skin or muscle). De liberate release of the toxin or contamination of foodstuff with C. botu- linum is consider ed a potential biological weapon with the adult lethal dose of toxin being <1mcg. The toxin is carried in the blood to cholinergic neu- romuscular junctions where it binds irreversib ly. Symptoms begin between six hours and eight days after contamination and are more severe with earlier onset. Botulism is diagnosed by isolating C. from the stool, gastric aspirate or wound, or by mouse bioassay (survival of immunized mice and death of non-immunized mice when infected serum is injected). Clinical features \200 Symptoms include gastrointestinal disturbance, sore throat, fatigue, dizziness, paraesthesi ae, cranial involvement, and a progressive, descending \202 accid weakness. Parasympathet ic symptoms are common. The disease is usually self-limiting within several weeks. \200 Management Antibiotics are not indicated for the management of botulism unless there is a c ontaminated wound. Respiratory care Regular spirometry and mechanical ventilation if FVC <1L. Patients with bu lbar palsy need intubation for airway protection. Toxin removal If there is no ileus, the use of non-magnesium containing cathartics (e.g. so rbitol) may remove the toxin load. Magnesium may enhance the effect of the toxin. Antitoxin Prevents further paralysis but does not reverse existing paralysis. May shorten t he course of the disease if given early. There is a risk of anaphy- lactoid reactions, but usually treatment is limited to two doses minimizing the risk. Wound botulism Surgical debridement (after antitoxin treatment to neutralize any toxin rele ased during sugery), benzylpenicillin 1.2g IV 6-hourly and metronida- zole 500mg IV 8-hourl y, and antitoxin are the mainstays of treatment for contaminated wounds. BOTULISM 465 Key paper Brett MM, Hallas G, Mpamugo O. (2004) Wound botulism in the UK and Ireland. J Med Microbiol 53: 555 \200\22361. See also: Airway maintenance, p40; Endotracheal intubation, p42; Ventilatory support \200 \224indications, p44; Antimicrobials, p326; Respiratory failure, p350; Bradyarrhythmias, p3 86. This page intentionally left blank 467 Chapter 28 Hematological disorders Bleeding disorders 468 Clotting disorders 470 Anemia 472 Sickle cell disease 474 Haemolysis 476 Platelet disorders 478 468 CHAPTER 28 Hematological disorders Bleeding disorders A common problem in the critically ill, this may be due to: (i) large ve ssel bleeding \200\224usually \200\230surgical \200\231 or following a procedure (e.g. che st drain, tra- cheostomy, accidental arterial puncture, removal of intravenous or intra- ar terial catheter); peptic ulcer bleeding is now relatively uncommon due to improved attentio n to perfusion and nutrition; (ii) around vascular cath- eter sites or from intubated/instr umented lumens and ori \201 ces \200\224usually related to severe multisystem illness or e xcess anticoagulant therapy, including thrombolytics; (iii) small vessel bleeding, e.g. ski n petechiae, gastric erosions \200\224usually related to anticoagulation or severe generali zed illness, including disseminated intravascular coagulation. Common ICU causes \200 \200 \200 Decreased platelet production, e.g. sepsis- or drug-induced. Decreased production of coagul ation factors, e.g. liver failure. Increased consumption, e.g. DIC, trauma, bleeding, hepar in-induced thrombocytopaenia, antiplatelet antibodies, extracorporeal circuits. Impaired or deranged platelet function. Drugs, e.g. heparin, aspirin, antibiotics. Decreased protease inhibitors, e.g. antithrombin, protein S, and protein C de \201 ciency (following sepsis). \200 \200 Principles of management 1. Transfuse platelets according to indications in the table. 2. A ntiplatelet medication taken in the past 1 \200\2232 weeks may affect platelet function, re sulting in bleeding despite a normal platelet count. One pool of platelets may be occasiona lly indicated. Abciximab, acting on glycoprotein 2b/3a, has an antiplatelet effect so patie nts may be atincreased risk of surgical bleeding. Platelets should be made available, but u sed only for excessive oozing/bleeding. 3. Abnormalities of the prothrombin time (PT) may be due to liver impairment or poor nutrit ional status. Vitamin K, orally or IV, is indi- cated. FFP is not needed unless signi \201 cant bleeding occurs. 4. In patients on warfarin, urgent reversal of INR may be indicated. 1mg vitamin K will rev erse warfarin within 4 \200\2236h while 10mg will saturate liver stores, preventing warfari n activity for >1 week. Prothrombin complex (e.g. Octaplex , Beriplex ) will correct INR within 20 \200\22330min. Vitamin K (2mg) must be given with the infusion. In a life-threate ning bleed due to warfarin, 5mg vitamin K and 50U/kg of prothrombin complex is re- quired. FFP should not be used to reverse warfarin or to correct a slightly increased PT, unless as sociated with active bleeding, e.g. DIC. 5. For bleeding related to thrombolysis: (i) stop the drug infusion; (ii) give tranexamic acid 10mg/kg, repeated 6 \200\2238 hourly; (iii) gi ve 4 units FFP. 6. Cryoprecipitate is rarely needed. Consider when thrombin time is elevate d and \201 brinogen is reduced, e.g. with DIC. Standard FFP con- tains \201 binogen and may be satisfactory. However, with \201 brinogen lev- els <1.0 and especially <0.5, cons ider cryoprecipitate. The aim is to increase \201 brinogen levels >1.5. Cryoprecipitate i s never indicated in patients with von Willebrand \200\231s disease or hemophilia. 7. Factor VIIa may be useful for severe, intractable bleeding once a stand- ard clotting sc reen and platelet levels have been fully corrected. Further studies are needed to con \201 rm its ef \201 cacy. BLEEDING DISORDERS 469 Management of major bleeding 1. If external, direct occlusion/deep suture. 2. Urgent expert opinion, e.g. for surgery, endoscopy + injection, etc. 3. Correct coagulopathy. Consider u se of factor VIIa if very severe and not surgically remediable. Management of vascular catheter or percutaneous drain site bleeding 1. Direct pressure/occl usive dressing. 2. Correct coagulopathy; consider use of tranexamic acid. 3. Surgical inter vention is rarely necessary although perforation/lacera- tion of local artery/vein should b e considered if bleeding fails to stop or becomes signi \201 cant. Indications for platelet transfusion Platelet count <10 x 109/L <20 x 109/L Situation Always Acute bleeding, sepsis, concurrent use of antibiotics, or other abnormalities of haemostasi s. A single pool is normally enough. <50 x 109/L DIC or invasive procedures, e.g. insertion of indwelling catheters, transbronchial biopsy, laparotomy <80 x 109/L <100 x 109/L Epidurals and lumbar punctures Procedures involving closed sites such as surgery to the eyes or brain See also: Full blood count, p220; Coagulation monitoring, p222; Blood transfusion, p248; Bl ood products, p250; Coagulants and anti \201 brinolytics, p322. 470 CHAPTER 28 Hematological disorders Clotting disorders Although critically ill patients often tend to be auto-anticoagulated, t he risk of major venous thrombosis increases with long-term immobility and paralysis and in speci \201 c pro-thrombotic conditions such as preg- nancy, thrombotic thrombocytopaenic purpura, SLE (lupus anticoagulant), sickle cell crisis, hyperosmolar diabetic coma, heparin -induced thrombo- cytopaenia syndrome (HITS), and congenital or acquired protein C or prote in S de \201 ciency. Disseminated intravascular coagulation is associated with microvascular clotting, a consumption coagulopathy, and increased \201 brinolysis. Clotting of extracorporeal circuits, e.g. for renal replacement therapy, may be due to: (i) mechanical obstruction to \202 ow, e.g. kinked catheter; (ii) inadequate anticoagulation ; or (iii) in severe illness, a decrease in endogenous anticoagulants (e.g. antithrombin II I); this may result in circuit blockage despite a coexisting thrombocytopaenia and/or coagu lopathy. Axillary vein or subclavian vein thrombosis may result from indwelling intravenous catheters. Management 1. All patients should be given TED (thromboembolic disease) stock- ings (grade II), preferably above the knee. Exceptions are patients with arterial vascular disease or t hose in whom the stockings do not \201 t. 2. If the patient is not auto-anticoagulated, g ive prophylactic LMW heparin (5000IU od SC) for long-term immobility/paralysis, and to high -risk patients (e.g. previous DVT, femoral fractures). 3. For pulmonary embolism or deep vein thrombosis, give 200IU/kg SC daily (or 100 IU/kg bd if at risk of bleeding). 4. Partial thromboplastin times (PTT) should be checked regularly if giving unfractionated heparin and maintained at approximately 2 \200\2233x normal. Monitoring is not necessary fo r LMW heparin though anti- factor Xa levels can be used. 5. Intra-arterial clot can be treated with local infusion of thrombolytics, usually followed by heparinisation. Seek vascular surgical advice. 6. Axillary vein or subclavian vein thrombosis should be managed by elevation of the affect ed arm, e.g. in a Bradford sling, and heparinisation. 7. Speci \201 c conditions may requi re speci \201 c therapies e.g. plasma exchange for SLE and TTP, whole blood exchange for sickle cell crisis. 8. If HITS is suspected, stop all heparin infusions (including arterial cath- eter \202 u sh) and treat with either danapranoid or hirudin. Con \201 rm with an antibody test. 9. Warfarinisation should be avoided until the platelet count is within the normal range as it may exacerbate the prothrombotic risk. CLOTTING DISORDERS 471 See also: Full blood count, p220; Coagulation monitoring, p222; Anticoagulants, p318. 472 CHAPTER 28 Hematological disorders Anemia De \201 ned as a low hemoglobin due to a decreased red cell mass, it may also be \200\230physiological \200\231 due to dilution from an increased plasma volume, e.g. pregna ncy, vasodilated states. Major causes in the ICU patient \200 \200 Blood loss, e.g. hemorrhage, regular blood sampling. Severe illness \200\224analogous to th e \200\230anemia of chronic disease \200\231, there is decreased marrow production and, po ssibly, a decreased lifespan. Rarer causes include: \200 \200 \200 \200 \200 \200 Microcytic anemia \200\224predominantly iron de \201 ciency. Normocytic \200\224chronic di sease. Bone marrow failure (idiopathic, drugs, neoplasm, radiation). Haemolysis. Renal fail ure. Macrocytic \200\224vitamin B12 and folate de \201 ciency, alcoholism, cirrhosis, side roblastic anemia, hypothyroidism. Congenital diseases \200\224sickle cell, thalassaemia. Management 1. Treatment of the cause where possible. 2. Blood transfusion: \200 The ideal hemoglobin level for optimal oxygen carriage and viscosity remains contentious. A multicentre trial showed improved outcomes if a trigger of 7g/dL was used though this was with non-leukodepleted blood which is now rarely used. A higher transfusion threshold, e.g. 9 \200\22310g/dL or higher, may potentially bene \201 t those with cardiorespiratory dise ase although prospective trial data are lacking. Transfusion is usually given as packed cel ls. This may need to be given rapidly during active blood loss or slowly (over 4h) for corr ection of a gradually falling hemoglobin level. In patients needing massive blood transfusi on, ensure adequate correction of plasma and platelets to prevent dilutional coagulopathy. For each 6 \200\2238 units of packed red cells, give FFP 10 \200\22315mL/kg (approx. three bags for a 70kg person), a pool of platelets, and 1 unit of cryoprecipitate. Rarely, patien ts admitted with a chronically low hemoglobin, e.g. <4 \200\2235g/dL, which often follows l ong-term malnutrition or vitamin de \201 ciency, will need a much slower elevation in hemo globin level to avoid precipitating acute heart failure. Thiamine should be co-administered . An initial target of 7 \200\2238g/dL is often acceptable. Obviously, this may need to be altered in the light of any concurrent acute illness, where elevation of oxygen delivery is deemed necessary, or with a concurrent acute hemorrhage. In patients with B12 de \201 cie ncy, blood transfusion should not be given without discussion. Treat with B12 injections. E rythropoeitin reduces the need for blood transfusion in long-term ICU patients, and may be useful in those with multiple antibodies or declining transfusion for religious reasons. Pr ospective studies found no mortality bene \201 t except in the subgroup admitted following trauma. However, there was a signi \201 cant increase in thrombotic events. anemia 473 Key papers H bert PC, Wells G, Blajchman MA, et al. for the Transfusion Requirements in Cr itical Care Investigators, Canadian Critical Care Trials Group. (1999) A multicentre, rando mized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 340: 409 \200\22317. Corwin HL, Gettinger A, Fabian TC, et al. for the EPO Critical Care Trials Group. (2007) Ef \201 cacy and safety of Epoetin Alfa in critically ill patients. N Engl J Med 357: 965 \200\22376. See also: Full blood count, p220; Blood transfusion, p248. 474 CHAPTER 28 Hematological disorders Sickle cell disease A chronic, hereditary disease almost entirely con \201 ned to the blac k popu- lation where the gene for Hb S is inherited from each parent. The red blood cells l ack Hb A; when deprived of oxygen, these cells assume sickle shapes, resulting in erythrost asis, occlusion of blood vessels, thrombosis, and tissue infarction. After stasis, cells ar e more fragile and prone to haemolysis. Occasionally, there may be bone marrow failure. Chronic features Patients with sickle cell disease are chronically anemic (7 \200\2238g/dL) with a hyperdynamic circulation. Splenomegaly is common in youth, but with progressive epi sodes of infarction, splenic atrophy occurs leading to an increased risk of infection, part icularly pneumococcal. Chronic features include skin ulcers, renal failure, avascular bone necrosis (9 supervening osteomyelitis, especially Salmonella), hepatomegaly, jaun- dice, and cardiomyopathy. Sudde n cardiac death is not uncommon, usually before the age of 30. Sickle cell crises Crises are precipitated by various triggers, e.g. hypoxaemia (air travel , anesthesia, etc.), infection, cold, dehydration, and emotional stress. Thrombotic crisis This occurs most frequently in the bones or joints, but also affect chest and abdomen, giving rise to severe pain. Occasionally, neurological symp- toms (e.g. seizu res, focal signs), haematuria, or priapism may be present. Pulmonary crisis is common; seco ndary chest infection or ARDS may supervene, worsening hypoxaemia, and further exacerbating the crisis. Aplastic crisis Related to parvovirus infection, it is suggested by worsening anemia and a reduction in the normally elevated reticulocyte count (10 \200\22320%). Haemolytic crisis Intravascular haemolysis with haemoglobinuria, jaundice, and renal failur e sometimes occurs. Sequestration crisis Rapid hepatic and splenic enlargement due to red cell trapping with se vere anemia. This condition is particularly serious. Management Prophylaxis against crisis includes avoidance of hypoxaemia, other known precipi tating factors, prophylactic penicillin, and pneumococcal vaccine. 1. Painful crises usuall y require prompt opiate infusions. Although psy- chological dependence is a risk in a small number of patients, analgesia should not be withheld. 2. Give oxygen to maintain SaO2 at 97 \200\22399%. Avoid hyperoxia. 3. Rehydrate with intra venous \202 uids and keep warm. 4. If infection is suspected, antibiotics should be given as indicated. 5. Transfuse blood if hemoglobin falls. In central nervous respiratory cri- sis, perform red cell exchange (manual or via apheresis). 6. Lower proportion of sickle cells to <30% by exchange transfusion. 7. Mechanical ventilat ion may be necessary for chest crises. SICKLE CELL DISEASE 475 See also: Oxygen therapy, p38; Full blood count, p220; Blood transfusion, p248; Non-opioid analgesics, p302; Opioid analgesics, p304; Antimicrobials, p326; Anemia, p472; Haemolysis, p476; Pain, p618. 476 CHAPTER 28 Hematological disorders Haemolysis Shortening of erythrocyte lifespan below the expected 120 days. Marked intravasc ular haemolysis may lead to jaundice and haemoglobinuria. Causes \200 \200 \200 \200 \200 Blood transfusion reactions. Malaria. Sickle cell haemolytic crisis. Drugs, e.g. high-dose penicillin, methyl dopa. Autoimmune (cold or warm antibody-mediated) \200\224may be idiopat hic or secondary, e.g. lymphoma, SLE, mycoplasma. Haemolytic uraemic syndrome/thrombotic th rombocytopaenic purpura (microangiopathic haemolytic anemia). Trauma (cardiac valve prosthe sis). Glucose-6-phosphate dehydrogenase de \201 ciency \200\224oxidative crises occur foll owing ingestion of fava beans or administration of drugs (e.g. primaquine, sulphonamides) l eading to rapid onset anemia and jaundice. \200 Diagnosis \200 Unconjugated hyperbilirubinaemia, increased urinary urobilinogen (increased RBC breakdown). Reticulocytosis (increased RBC production). Splenic hypertrophy (extravascular haemolysis) . Methaemoglobinaemia, haemoglobinuria, free plasma hemoglobin (intravascular haemolysis), reduced serum haptoglobins. RBC fragmentation (microangiopathic haemolytic anemia). Coombs \200\231 test (immune-mediated haemolysis). Other (including hemoglobin electrophoresis, bo ne marrow biopsy). \200 \200 \200 \200 Management 1. Identi \201 cation and speci \201 c treatment of the cause where possible. 2. Blood transfusion to maintain hemoglobin >7g/dL. 3. Massive intravascular haemolysis may lead to acute renal failure. Maintain a good diuresis and haemo(dia) \201 lter if necessary. HAEMOLYSIS 477 See also: Full blood count, p220; Blood transfusion, p248; Anemia, p472; Sickle cell diseas e, p474; Malaria, p568; SARS, VHF, and H5N1, p570. 478 CHAPTER 28 Hematological disorders Platelet disorders Thrombocytopaenia Rarely symptomatic until the platelet count <50 x 109/ L; spontaneous bleeding is more likely when the count <20 x 109/L. Although bleeding is oft en minor, e.g. skin petechiae, oozing at intravascular catheter sites, it may be massive or life-threatening, e.g. haemoptysis, intracranial hemorrhage. Causes \200 Sepsis \200\224a common cause of a low platelet count in the critically ill; it is often a barometer of either recovery or deterioration. Disseminated intravascular coagulation. Drug s. Related to antiplatelet antibody production, e.g. heparin (heparin- induced thrombocytop aenia syndrome, HITS), sulphonamides, quinine. Resulting in bone marrow suppression, e.g. c hemotherapy agents. Others, e.g. aspirin, chlorpromazine, prochlorperazine, digoxin. Follow ing massive bleeding and multiple blood transfusions. Bone marrow failure, e.g. tumor in \201 ltration, drugs. Splenomegaly. Thrombotic thrombocytopaenic purpura (TTP), haemolytic uraemic syndrome (HUS). Idiopathic thrombocytopaenic purpura (ITP). Speci \201 c infection s, e.g. measles, infectious mononucleosis, typhus. Collagen vascular diseases, e.g. SLE. \200 \200 \200 \200 \200 \200 \200 \200 \200 Management 1. Treat the cause, e.g. antibiotics for sepsis, stopping offending drugs, plasm a exchange for TTP, splenectomy and corticosteroids for ITP. 2. Platelet support: \200 Platelet transfusions in an otherwise well person with no signi \201 cant bleeding can be withheld until the count falls <10 x 109/L. Give 1 \200\2232 pools if count <50 x 109/L and either bleeding, septic or due to undergo surgery/invasive procedure. For CNS or eye surge ry, aim for counts >100 x 109/L. Platelet transfusion is contraindicated in TTP, HUS, and H ITS. Deranged platelet function Function may be deranged albeit with normal counts, e.g. followi ng aspirin within past 1 \200\2232 weeks, epoprostenol, uraemia. Fresh platelets may be req uired if the patient is symptomatic. In uraemia, one dose of vasopressin (20mcg IV over 30m in) may be useful before surgery. Thrombocythaemia Rare in ICU patients; platelet counts of ten exceed 800 x 109/L. Causes Prolonged disorders. Essential (idiopathic) thrombocythaemia is unusual. Management As the major risk is thrombosis, management is based upon mobilizin g the patient and administration of either prophylactic aspirin (150mg bd PO) or LMW hepari n (5000IU od SC). Dipyridamole (300 \200\223600mg tds PO) is occasionally used. low level bleeding, post-splenectomy, myeloproliferative PLATELET DISORDERS 479 See also: Plasma exchange, p114; Full blood count, p220; Blood products, p250; Anticoagulan ts, p318; Corticosteroids, p328. This page intentionally left blank 481 Chapter 29 Metabolic disorders Electrolyte management 482 Hypernatraemia 484 Hyponatraemia 486 Hyperkalaemia 488 Hypokalae mia 490 Hypomagnesaemia 492 Hypercalcaemia 494 Hypocalcaemia 496 Hypophosphataemia 498 Gene ral acid-base principles 500 Metabolic acidosis 502 Metabolic alkalosis 504 Hypoglycaemia 5 06 Hyperglycaemia 508 Diabetic ketoacidosis 510 Hyperosmolar diabetic emergencies 512 Thyro id emergencies 514 Hypoadrenal crisis 516 482 CHAPTER 29 Metabolic disorders Electrolyte management A balance must be achieved between electrolyte intake and output. In electrolyte disturbance consider: \200 \200 \200 \200 Altered intake. Impaired renal excretion. Increased body losses. Body compartment redistrib ution (e.g. increased capillary leak, secondary hyperaldosteronism). As well as Na+ and K+, consider Mg2+, Ca2+, Cl \200\223 and PO4 3 \200\223 balance. Plasma electrolyte values are poorly re \202 ective of whole body stores; however, excessi vely high or low plasma levels may induce symptoms, and deleterious physiological and metab olic sequelae. Water balance must also be taken into account; depletion or excess repletion may, respectively, concentrate or dilute electrolyte levels. Gravitational peripheral oedema implies increased total body Na+ and water though intravascular salt and water depletion may coexist. The usual daily requiremen ts of Na+ and K+ are 60 \200\22380mmol. Electrolyte losses \200 \200 \200 \200 \200 Na+, Cl \200\223 Na+, Cl \200\223 Na+, Cl \200\223, K+, Mg2+ Na+, Cl \200\223, K+, Mg2+ Na+ , Cl \200\223, K+ Large nasogastric aspirate, vomiting Sweating Polyuria Diarrhea Ascitic drainage