Cognitive problems affect outcome Failure to motivate a self-directed recovery program is o ften due to unrecognized cognitive problems, slowed information processing, short-term memo ry impairment and reduced new learning and executive skills. These prob- lems reduce insigh t, intitiative, attention and concentration. Psychology input to the patient and the team c an support new learning strategies recovery and adaptation. The talking therapies There are many. Cognitive behavioral treatment (CBT), Person-centered therapy (CPT), solution-focused brief therapy (SFBT), rewind theory and others all have th eir advocates. Counseling treatments encourage adjustment using a spectrum of methods that span re \202 ective through to directive techniques. Most are based on frequent ses- sions , identifying negative patterns of behavior and desired changes. Anxiety or depressive illn ess may also respond well to short-term pharmacological therapy. How to do it Moving into rehabilitation should give the patient the opportunity to work on impairments, reduce disability and develop a discharge plan. It is a simple problem-solving process, and depends on team work and clarity of thinking. The key qualities of successful rehabilitation team mem- bers are good communication skills, expertise and \202 exibil- ity. Each patient has a personalized rehabilitation plan which includes: 1 Meeting ongoing surgical and medical needs 2 Assessing and observing cognition, communication skills Novel home-based therapies In the future, traditional therapist-based services may be suppl emented by virtual environments, teletherapy, porta- ble robotic devices employing errorles s learning systems and positive feedback. These methods are unlikely to be superior, but ca n enrich and vary the exercise environment and allow the patient greater control and applic ation. and emotional state 3 Assessing physical impairments and functional de \201 cits 4 Appraisal of the social sit uation, home environment and potential for later return to work Knowledge of these permits the development of a rehabili- tation program and discharge plan which should include 1 Expected outcome \200\224managing expectations 2 Identi \201 catio n of discharge destination 3 Expected date of discharge 4 Advice on work and driving 5 Refe rral on to community resources. This should be according to need but is often modi \201 ed by availability. Further reading Combes A, CostaMA, Troillet JL, et al. Morbidity, mortality and qual- ity o f life outcomes of patients requiring 14 days of mechanical ventilation. Crit Care Med 2003 ; 315: 1373 \200\22381. Elliott D, McKinley S, Alison JA, et al. Study protocol: home based physical rehabilitation for surviviors of a critical illness. Crit Care 2006; 10: R90. Jones C, Skirrow P, Grif \201 ths RD, et al. Rehabilitation after critical illness: a rand omized controlled trial. Crit Care Med 2003; 31: 2456 \200\22361. Goal planning This is the key to active, outcome-driven rehabilitation and can be used to b ridge the gap between hospital and home, with the patient being an active driver of the pro cess, and on discharge taking full responsibility to set goals to achieve continuing recove ry after discharge. \200\230SMART \200\231 goals (Speci \201 c, Measurable, Appropriate, Relevant, Timely) are informed by experienced staff who have a reasonable Latronica N, Shehu I, Seghelini E. Neuromuscular sequela of critical illness polyneuropathy. Curr Opin Crit Care 2005; 11: 381 \200\22390. Van der Schaaf M, Beelen A, de Vos R. Functional outcome in patients with critical illness polyneuropathy Disabil Rehabil 2004; 26: 1189 \200\22397. 384 A COHEN Hyperthermias through its effect on intracellular calcium metabolism. This switches off heat production i n conditions such as malignant hyperthermia. Cooling will be inhibited by drugs that advers ely affect normal heat loss mechanisms such as anticholinergic agents which inhibit sweatin g. Under normal circumstances, body temperature is closely controlled around a set point close to 37 C by balancing heat production and loss. Pyrexia can be a complicating factor in cr itical illness or a reason for admission to inten- sive care in its own right. The term hyp erthermia is often used interchangeably with hyperpyrexia but can more accurately be de \201 ned: Hyperpyrexia describes a situation in which the set point for temperature is rais ed, e.g. by infection. Hyperthermia is an elevation of body temperature due to an inability of control systems to function. This results from an imbalance between factors making the body hot and those allowing it to cool. Physical methods of cooling Simple methods of cooling rely on enhancing normal heat loss. E vaporative losses can be encouraged using a fan and sponging the skin. Direct cooling of th e skin can be achieved by using cold packs, but these may cause skin damage and will be ine ffective if they cause vasoconstriction. Specially designed cooling blankets based on cold water or air circu- lation are safe and more effective. Irrigation of various body cavities with cold \202 uid has been described, most commonly the bladder and stomach. Physiological effects of pyrexia Cardiovascular A high central temperature is associated wi th tachycardia, elevated cardiac output, low SVR and hypotension. This picture is seen when a patient in early sepsis is initially \202 uid resuscitated; failure to resuscitate ade quately would result in the same patient being peripherally cold and clammy. Extracorporeal cooling Special systems are available, but the majority of ICUs can rapidly deploy equipment they already have. Venovenous dia \201 ltration in its various guises is a common form of RRT. Usually these systems are heated in an attempt to prevent heat loss. Some patients with marked pyrexia may bene \201 t from connection to an extracorporeal cir cuit of this nature even when not in renal failure. Metabolic Tissue oxygen demand is increased in association with a rise in metabolic rate. P art of the effect on tissue oxygena- tion will be offset by a right shift in the oxyhaemogl obin dissociation curve, increasing availability of oxygen. Purpose-built cooling systems The desire actively to cool cardiac arrest patients has resul ted in the availability of a number of specially designed cooling systems. One of these is based on the use of an intravascular catheter with a specially designed cuff through which cool water is circulated. Alternative designs include tents that surround the patient payin g special attention to cooling of the neck region. A common characteristic of these systems is incorporation of sophisticated monitoring and control features. Immunological Temperature-sensitive pathogens are compromised by a rise in body temperature , while leucocyte activity is enhanced, thus promoting response to infection. Pyrexia complicating critical illness The most likely cause of pyrexia in a critically ill patient is response to sepsis. Temperature is regulated in the hypoth- alamus. Cytokine rel ease during sepsis results in activation of the arachidonic acid pathway and stimulation of heat production via PGE2. Some of the effects of pyrexia may confer a survival bene \201 t, but there comes a time when bene \201 ts are offset by disadvantages. Heat stroke When the normal methods of heat loss are overwhelmed an individual will gradual ly become hot and dehydrated. Heat stroke is typically seen in patients with compromised he at control systems such as the very young and old or when healthy individuals exercise in h ot and humid envi- ronments. Heat stroke is diagnosed in a hyperthermic patient with signi \201 cant neurological impairment such as altered consciousness or convulsions. These pati ents may or may not be sweating. MODs with rhabdomyolysis, disorders of clotting, renal and liver failure have all been described. In less severe cases, attention should be given to monitoring serum sodium and blood glucose, which can be high or low. Treatment involves bas ic resuscitation, removing the patient from the source of heat and rapidly facilitating coo ling. Speed of \202 uid resuscitation should be guided by clinical assessment, with invas ive monitoring if necessary. Choice of \202 uid may be guided by electrolyte determinatio n with special attention to the possibility of sodium depletion. Antipyretic agents are not indicated as abnormal body temperature control mech- anisms are not a feature of heat stro ke. Management of pyrexia Minimize heat gain Unwanted heat gain should be minimized by consider ing environmental factors such as sunlight, poor room ventila- tion, excessive bed clothing and overly warm humidi \201 ca- tion circuits. Intensive care rooms should have controlla ble temperature settings. Some patient cooling techniques may be impeded by shivering. If a patient does not require muscle relaxation for other reasons chlorpromazine may limit shiv ering. Treat obvious cause Infection should be investigated and treated, e.g. by drain- age of col lections and use of broad-spectrum antibiotics, or targeted therapy if possible. Drug therapy There are several ways in which drugs can be used to lower body temperature: \200 An elevated set point for temperature can be reset by antipyretic drugs such as paracetamol . Excessive heat production is a feature of some syndromes. Dantrolene is a drug that facil itates relaxation of muscle Hyperthermia syndromes A number of serious hyperthermia syndromes that require admission to intensive care are remarkable not only for 385 CHAPTER 22.13 Hyperthermias their similarities, such as high mortality if not treated aggressively, but also their diff erences. temperature similar to heat stroke. Similar complications occur, including rhabdomyolysis, renal failure and DIC. Hepatic damage can be seen in association with the initial insult or may develop some weeks later. This can progress to acute fulminate liver failure requiring transplantation. Management of ecstasy toxicity is similar to other hyper- thermias, with concentration on cooling, adequate \202 uid resuscitation and prevention of renal failure . Dantrolene has been used in this condition. Neurolept malignant syndrome This is an idiosyncratic reaction to antipsychotic medica- tio n. A wide range of drugs have been implicated such as haloperidol, promethazine, risperidon e and clozapine. A common feature of drugs precipitating the syndrome is their inhibitory e ffect on central dopaminergic receptors. Typically the syndrome develops within the \201 rst week of commencing medication. It is seen most frequently in young adult males. The syn drome is characterized by muscle rigidity, delirium and agitation. Temperature eleva- tion is seen, but may not be marked. Patients often have autonomic disturbance such as hypertens ion. Rhabdomyolysis leading to renal failure is an important complication. Laboratory inves tigations often show a leucocytosis, high creatinine kinase and liver dysfunction. Once the syndrome is recognized, any potential precipitat- ing agent should be withdrawn and pyrexi a and autonomic dysfunction should be managed symptomatically. Strategies should be impleme nted to minimize the effects of rhab- domyolysis and to protect renal function. Maintenance of an alkaline diuresis is probably more effective that other forms of therapy. Mannitol i s advocated by some, but should only be used where dehydration is not a concern. Drugs to t arget the pathological process have been used such as bromocritptine, which is a dopamine a gonist, and dantrolene, which should block the metabolic production of heat; their role rem ains unclear. Malignant hyperthermia (MH) Although rare, MH is well known to anesthetists as it is an imp ortant preventable cause of mortality under anesthesia. MH is caused by an abnormality of c alcium metabolism in muscle, resulting in sustained contraction and develop- ment of a hype rmetabolic state. It is inherited as an auto- somal dominant with incomplete penetrance. Ge netic mutations have been demonstrated in some patients, including several different mutati ons of the ryanodine receptor. MH occurs when the patient is exposed to a trig- ger agent s uch as a volatile anesthetic or suxamethonium. It may present clinically with muscle rigidi ty expressing itself as master spasm causing dif \201 cult intubation or as evi- dence of a hypermetabolic state detected with routine anesthetic monitoring. During anesthesia, the \201 rst signs of MH include an unexpected rise in end-tidal carbon diox- ide, tachycardi a, hypoxia and cyanosis. This may be accom- panied by ECG abnormalities and a temperature r ise. Blood gas analysis shows worsening acidosis. Clinically the patient rapidly deteriorat es with marked hyperthermia and severe metabolic derangement due to muscle cell damage. If they survive long enough without treatment, renal failure, myoglobinurea and other signs of a severe hyperthermia develop. The Association of Anesthetists guidelines for treatment st ress the need to halt the process by discontinuing trigger agents, administering dantrolene initially 2 \200\2233mg/kg and using active cooling. Dantrolne administered IV acts direct ly on the ryanodine receptor. Once the process is halted, the patient requires monitoring a nd symptomatic treatment including correction of acidosis with sodium bicarbonate, treatmen t of hyperkalaemia and alkaline diuresis. Following admission to intensive care, management needs to concen- trate on monitoring for the possibility of compartment syndrome due to oe dematous damaged muscle and recru- descence of MH. Ecstasy toxicity Hyperthermia is a well recognized complication of Ecstasy toxicity. The sy ndrome can be seen in some patients after taking a single tablet. Ecstasy is an amphetamine derivative, but tablets may be contaminated with other substances such as the hallucinogen ic agent mescaline. Ecstasy is thought to have a stimulant effect through central release o f dopamine. This is associated with sympathetic overactivity causing tach- ycardia, hyperte nsion and hyperthermia. Hallucinogenic effects are related to an initial release then deple tion of serotonin in the brain which causes euphoria, increased energy, altered time percep tion and other psychological changes which encourage an increase in sociability. Frequently the drug is taken in environments such as \200\230all-night raves \200\231 where large nu mbers of individuals congre- gate and dance for many hours on end. The drug \200\231s ten- dency to cause hyperthermia is aggravated by the hot environment, exercise over a number of hours and inade- quate \202 uid intake. A severe toxic response to Ecstasy is associated with loss of consciousness, seizures and a marked elevation in body Further reading Association of Anesthetists of Great Britain and Ireland. Management of a M alignant Hyperthermia Crisis. 2007. http://www.aagbi.org/publications/guidelines/ docs/mali gnanthyp07amended.pdf This page intentionally left blank 387 Chapter 23 Hematological disorders Chapter contents Bleeding disorders 388 Anemia in critical care 392 Sickle cell anemia 394 Haemolysis 396 Disseminated intravascular coagulation 398 Neutropenic sepsis 400 Hematologi cal malignancies in the ICU 404 Coagulation monitoring 406 388 S BRETT & J UPRICHARD Bleeding disorders Acquired bleeding disorders Consumptive coagulopathy (DIC) Inappropriate activation of the coagulation process. Usually presents as hemorrhage, but 5-10% may show micro- thrombi (e.g . digital ischaemia). Clinical associations: sepsis, trauma, obstetric emergencies, maligna ncy, hepatic failure, toxic reactions (e.g. transfusion reactions, snake bites) Diagnosis: Thrombocytopenia, prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), hypo \201 brinogenaemia, elevated \201 brin degradation products (FDPs) or D-di mers. Management: Treat the underlying disorder. In bleeding patients, platelet transfusion and replacement of coagulation factors with FFP and cryoprecipitate is indi- cated to main tain the platelet level >50 x 109/l, PT and APTT <1.5 times the normal control time and \201 brinogen >1g/l. The use of heparin is controversial. Low dose UFH (300 \200\223 500U/h ) has been used in patients with thrombotic mani- festations (e.g. gangrene), but caution s hould be exercised as it can provoke hemorrhage. Activated protein C (Drotrecogin alfa acti vated) has been shown to reduce mortality in certain cases of over- whelming sepsis. cases of lepirudin overdose. rVIIa has been used to mini- mize bleeding complications of bo th drugs. Antiplatelet therapy (e.g. aspirin, ticlopidine, clopidogrel, tiro \201 ban, abciximab) Ti ro \201 ban has a half-life of 10 \200\22315min and is renally excreted. The biological ha lf-life of abciximab is 18h. Aspirin is an irreversible inhibitor, so is effective for the lifetime of the platelet ( 7 days). If hemorrhage occurs with any of these drugs, then trea t- ment is with platelet transfusions. Thrombocytopenia Low automated platelet counts should be con \201 rmed by blood \201 lm examination. True thrombocytopenia is the result of decreased platelet production (e.g. bon e marrow hypoplasia or marrow in \201 l- tration), platelet sequestration (hypersplenism) or increased platelet destruction (immune or non-immune). Immune causes include SLE and dru gs such as quinine and heparin. Non-immune causes include microangiopathic haemolytic anaem ias such as thrombotic thrombocyto- penic purpura (TTP) and DIC. Septicaemia without DIC ca n cause thrombocytopenia. Drugs such as pipericillin may induce marrow aplasia and conseque nt thrombocyto- penia. Platelet transfusions are contraindicated in TTP and HIT. TTP is tre ated with plasma exchange. HIT requires cessa- tion of heparin and therapy with an alternat ive anticoagu- lant. Immune thrombocytopenia is treated with steroids (1mg/ kg/day predniso lone), IVIG (1g/kg/day for 2 days) or IV anti- D (75mcg/kg) in Rh(D)-positive individuals w ith function- ing spleens. In the face of major bleeding, steroids together with immunoglob ulin or anti-D may be given and then platelets can be transfused. Platelet refractoriness i s commonly non-immune, due to sepsis, drugs or splenomegaly. If no clinical reason can be d etermined, then human leucocyte antigen (HLA) antibod- ies should be sought in conjunction with hematological advice. Provision of HLA-matched platelets may improve transfusion respo nse. Dilutional coagulopathy (massive blood transfusion) De \201 ned as the loss of one blood v olume within a 24 h period. (Normal adult blood volume is 7% of the ideal body mass, i.e. 5l.) Coagulation factor de \201 ciency is unlikely until 80% of the blood volume has been replaced. Maintain the platelet count >50 x 109/l, PT and aPTT <1.5 times the normal contro l time and \201 brinogen >1g/l. Recombinant FVIIa (rVIIa) has been used in uncontrolled b leeding associated with trauma, although the results of RCTs have been disappointing. Doses have ranged from 50 to 200mcg/ kg. Bleeding in the anticoagulated patient Oral anticoagulants (e.g. warfarin) Major bleeding o n warfarin is 3%/yr. Treatment of overanticoagulation is with vitamin K (10mg IV). If hemo rrhage is present, then FFP (12 \200\22315ml/kg) or pro- thrombin complex concentrate (PCC) may be indicated. Hematological advice should be sought prior to the use of PCC due to thr ombogenicity. Liver disease All coagulation factors (except von Willebrand factor (vWF)) are synthesized in the liver. Reduced synthetic function of the liver results in prolongation of the screen - ing tests of coagulation (particularly the PT). In cholestatic liver disease there is red uced absorption of lipid-soluble vitamins, so reduced levels of vitamin K-dependent coagu- lation factors. Failure of the normal enzymatic removal of sialic acid from \201 brinogen results in dys \201 brinogenaemia. Treatment of bleeding in the context of liver disease will be determined by the results of coagulation tests (PT, aPTT, thrombin time (TT) and fi brinogen). Vitamin K should be given to aid synthesis of coagulation factors. FFP, cryoprec ipitate and platelet transfusions may also be needed. PT is used as an indicator for orthot opic liver transplanta- tion. FFP will arti \201 cially correct a prolonged PT and so shou ld be avoided in potential transplant candidates. Parenteral anticoagulants (e.g. heparin, lepirudin, danaparoid) UFH has a short half-life ( 30 \200\22360min) and can be reversed by protamine (1mg for each 100U heparin). LMWH has a half-life of 3 \200\2238h. Protamine can only reverse 50 \200\22370% of the dose. Lepirudin has a half-life of 30 \200\22360min. Danaparoid has a half-life of 24h. These drugs are pr incipally used in cases of HIT. There are no reversal agents for Lepirudin and Danaparoid. However, haemo \201 ltration has been used in 389 CHAPTER 23.1 Bleeding disorders Renal disease Platelet function is impaired in uraemia. Treatment of the anemia associated with renal disease partially corrects the prolonged bleeding time. 1-Deamino-D-arginine vas opressin (DDAVP) has also been shown to reduce the bleeding time. Acquired von Willebrand syndrome This has been described in association with myeloprolifera - tive disorders (usually only when the platelet count is >1000 x 109/l), paraproteinaemia and B-lymphoid malig- nancies. Control of the underlying disease stops the haem- orrhagic p henotype. Alcohol Excessive alcohol intake inhibits platelet aggregation and prolongs the bleeding ti me. Alcohol-induced cirrhosis results in a hypocoagulable state due to reduced synthesis of coagulation factors. Coagulation factor inhibitors These are autoantibodies directed against a coagulation facto r. They can appear de novo (acquired hemophilia) or result from exposure to factor concentr ate in a con- genital hemophiliac. They result in decreased activity of that factor and usu ally present with hemorrhage. In acquired hemophilia, they may be associated with autoimmun e disease, malignancy, drugs or post- partum. Treatment must include that of the underlying disorder (e.g. immunosuppression) and management of haemor- rhage. Patients may be resista nt to coagulation factor con- centrates, and a bypassing agent (such as FEIBA or rVIIa) may be needed. Vitamin K de \201 ciency Vitamin K is essential for the synthesis of fully functional coag ulation factors II, VII, IX, X, protein C and protein S. Patients with a poor diet, malabso rption or those requiring TPN may become de \201 cient. In addition, absorption may be red uced in cholestatic liver disease. Consequences can be prevented by the IV administration o f vitamin K (10mg weekly). Hypothermia and acidosis Most of the coagulation factors are enzymes or cofactors in enzyma tic reactions. Their activity is greatest at physiological temperature and pH. Pre-warmed \202 uids should be used in resuscitation of the trauma patient. pH has been shown to be o f greater importance than tem- perature in the likelihood of success with rVIIa. Congenital bleeding disorders Hemophilia A and B The severity of hemorrhage is inversely co rrelated with the coagulation factor level. Haemarthroses and muscle haematomas are the mos t common sites of bleed- ing. However, in the ITU setting, trauma and surgery are most like ly to result in life-threatening hemorrhage if not managed appropriately. Treatment is with recombinant or plasma-derived factor VIII (FVIII) or IX, either by con- tinuous infusion o r by repeated bolus injections. Trough levels of the relevant factor should be measured to guide dosing. Inhibitors may develop, and management is as for acquired hemophilia (see abo ve). Cardiopulmonary bypass and cardiac disease The extracorporeal circuit is routinely heparini zed with UFH to prevent thrombosis during cardiac bypass. Heparin is reversed at the end of the operation by infusion of pro- tamine. However, excess use of protamine can result in a consumptive coagulopathy and hemorrhage. Following initial neutralization by protamine, he parin may be detected 2 \200\2236h later in the circulation due to the release of extravas- cular sequestered heparin. Thrombocytopenia frequently occurs due to platelet dam- age in the extracorporeal circuit. This is usually self-limiting and corrects within 2 \200\2233h. Aprotinin has been shown to reduce hemorrhage in high- risk cardiac patients but other ris ks may outweigh bene \201 t. Cardiac patients are often taking antiplatelet agents pre- op eration, and so transfusion of platelets may be indicated irrespective of the absolute coun t. von Willebrand disease This is the most common inherited bleeding disorder, with a prevalen ce of 1%. vWF promotes the binding of platelets to damaged subendothelium and, as a carrier of FVIII, it helps to localize the haemostatic reaction to the site of injury. von Willebr and disease usually results in mucosal bleeding. Life-threatening hemorrhage is unusual. Tr eatment is with DDAVP or intermediate purity FVIII concentrate. Platelet disorders These are characterized by mucosal bleeding and exces- sive hemorrhage f ollowing surgical challenge. They usually respond to DDAVP, but platelet transfusion may be needed. rVIIa has also been used. Paraproteinaemia and amyloidosis High levels of circulating immunoglobulins may impair plat elet function. Immunoglobulins may have activity as inhibitors of coagulation factors (see below). Paraproteinaemia may be associated with AL amyloidosis. This may in \201 ltrate sm all blood vessels and result in haem- orrhage. Autosomal recessive coagulation disorders Hemorrhage is usually less severe than in hemophi lia A or B. Treatment is with the appropriate factor concentrate or FFP. Hereditary haemorrhagic telangiectasia This disorder results in the proliferation of abnorm ally fragile blood vessels. Bleeding occurs following minor trauma. It may be associated wi th cerebral and pulmonary AV malformations. Haemorrhagic episodes may be reduced by oral oe strogens. Acute promyelocytic leukemia In this speci \201 c category of acute myeloid leukemia, the leukaemic cells are believed to express high levels of tissue factor which predisposes to D IC. Coagulation screening tests are deranged. Aggressive transfusion of FFP, cryopre- cipit ate and platelets is often necessary. 390 S BRETT & J UPRICHARD Ehlers \200\223Danlos syndrome This and other connective tissue disorders may present with skin hemorrhage. Abnormal collagen results in recur- rent stretching of the skin and subseq uent bleeding. Treatment of haemorrhagic episodes is with platelet trans- fusion. Demp \202 e C-E. Coagulopathy of sepsis. Thromb Haemost 2004; 91: 213 \200\22324. Hoffman M, Monroe DM, 3rd. A cell-based model of hemostasis. Thromb Haemost 2001; 85: 958 \200\22365. Mittal S, Watson HG. A critical appraisal of the use of recombinant factor VIIa in acquired bleeding conditions. Br J Haematol 2006; 133: 355 \200\22363. Stainsby D, MacLennan S, Thomas D, et al. Guidelines on the management of massive blood los s. Br J Haematol 2006; 135: 634 \200\22341. Further reading British Committee for Standards in Hematology, Blood Transfusion Task Force . Guidelines for the use of platelet transfusions. Br J Haematol 2003; 22: 10 \200\22323. This page intentionally left blank 392 A RETTER & BJ HUNT Anemia in critical care De \201 nition Anemia is de \201 ned as a hemoglobin concentration in the blood of <13.5g /dl in an adult male and <12g/dl in an adult female. Anemia is a frequent \201 nding in t he critically ill. 50% of patients are anemic on admission to the ICU, and this \201 g- u re rises to 95%. by the third day. These patients are exten- sively transfused, and 50% wi ll receive at least 5 units of packed red cells. prompting ICU admission and may signi \201 cantly complicate individual patient care. The reticulocyte count provides an assessment of red cell production. Microcytic anemia Normocytic anemia Macrocytic anemia Low MCV and MCH Normal MCV and MCH High MCV Iron de \201 ciency Acute blood loss B12 and folate de \201 ciency Pathogenesis Anemia in the critically ill is multi-factorial. Primary fac- tors include blo od loss from trauma, GI bleeding, contin- ued blood loss after surgery and RRT. The anemia is compounded by impaired red cell synthesis and intensive phlebotomy. The reason for reduc ed red cell production is unclear. Patients have anemia of chronic disease, i.e a low serum iron and total iron binding capacity with a high serum ferritin. The fall in serum iron co ncentration is pre- cipitated by a rise in hepcidin. Hepcidin inhibits cellular ef \202 ux of iron by binding to and inducing degredation of ferroportin, the sole iron exporter in t ransporting cells. Hepcidin synthesis is greatly increased during in \202 ammation under t he in \202 uence of the proin \202 ammatory cytokine IL-6. Erythropoesis is further impai red by the reduced release of erythropoietin and by a blunted marrow response to its action . Previous studies suggest that decreased serum iron may be protective against infection an d possibly mycobac- teria. Anemia of chronic disease Anemia of chronic disease Drugs Thalassaemia trait Hypothyroidism Haemolysis Hypopituitarism Myelodysplastic syndrome Mixed B12 and iron de \201 ciency MCH = mean corpuscular hemoglobin; MCV = mean corpuscular volume. Classi \201 cation of anemia Management of anemia in critical care Pre-existing causes of anemia can be rapidly diagnose d and the appropriate treatment started. The anemia of critical illness is managed with sup portive transfusion ther- apy. The CRIT and the Anemia in Blood Transfusion in Critical Car e (ABC) studies show that red cell transfusion is independently associated with an increase d mortality. This research builds on the earlier \201 nding by H rbert of a trend toward a decreased mortality in critically ill patients who were randomized to receive a restrict ive vs a liberal transfusion strategy. These studies form the basis of the current National Blood Service (NBS) recommendation of withholding transfusion until the hemoglobin falls b elow 8.0g/dl. Speci \201 c exclusions apply to patients with active ischaemic heart diseas e or severe sepsis or those who are actively bleeding. To confuse matters further, the SOAP study showed no association between increased mortality and blood transfusion. The bene \201 cial effect of leucodeple- tion has been suggested as the explanation for the con \202 ict- ing results seen with the SOAP data and the previous studies. Leucodepletion redu ces the risks of transmission of cell-associated viruses, prion transmission, transfusion- related febrile reactions and transfusion-related ALI. Therefore, by making transfusion saf er, the threshold may rise. With the continued debate regarding the risk:bene \201 t ratio of the transfusion threshold need to be more closely evaluated. A single measure of a targ et hemoglobin is easy to apply but probably too simplistic. The optimal haemo- globin conce ntration will vary for individuals, and some consideration of the serum lactate and mixed v enous oxy- gen saturation may be used in the future to help further evaluate the need for t ransfusion. Once a decision to transfuse has been made, there are no data to guide the numb er of red cell units that should be transfused. Single unit transfusions are of little clin ical ben- e \201 t and place increased logistical demands on local transfu- sion services, and are usually not recommended. There is no evidence to show that single unit transfusion s reduce Consequences of anemia End-organ function is dependent on the adequate delivery of oxygen t o cells, due to appropriate cardiac output and arterial oxygen content. Arterial oxygen con tent is directly proportional to the concentration of hemoglobin. When hemoglobin concentra tion decreases, oxygen-carrying capacity is reduced. If the intravascular volume is preserv ed, increased cardiac output maintains adequate tissue oxygen delivery. In addition, there is a rightward shift of the hae- moglobin \200\223oxygen dissociation curve where oxygen is more preferentially released to the tissues. Oxygen deliv- ery is redirected from non-vita l organs such as the splanch- nic bed. Studies in healthy adults show that these mechanisms can safely compensate until the haematocrit falls below 10% (this roughly equilibrates to a hemoglobin of 5g/dl). Below this level, oxygen de \201 cit leads to signi \201 cant org an impairment. Anemia may impair recovery from ill- ness. The critically ill are particular ly susceptible to the deleterious effects of anemia as the cardiac output is impaired in a substantial proportion of patients. These basic and logical assumptions have driven transfu sion prac- tice for many years. Approach to the investigation of anemia The initial approach should focus on determining th e severity of the anemia and the rapidity with which it has developed. Classically anemia i s characterized as micro- cytic, normocytic and macrocytic. This is a useful frame- work on which to base further investigations. A blood \201 lm will rapidly provide evidence of h aemolysis, iron de \201 ciency, B12 or folate de \201 ciency, underlying malignancy, a mi croan- giopathic haemolytic anemia or underlying hemoglobin- opathy. These conditions may p re-date the condition