there is suspicion of infective meningitis. 2 Look for evidence of viral infection. Association of syndrome with HIV, SLE, cyclosporin usage and the 3rd trimester of pregnancy. Treatment is a hematological emergency \200\224seek expert help immediately 1. Unless antecubital venous access is excellent, insert a large bore central apheresis catheter (may need blood product support). 2. May need ITU level of care and ventilation. 3. Initiate plasmapheresis as soon as possib le. Exchange 1 \200\2231.5 plasma volume daily until clinical improvement. May need 3 \200 \2234L exchanges. Replacement fluid should be solely FFP. In the event of delayed access to cell separator facilities, start IV infu- sions of FFP making intravascular space with diu retics if necessary. Once response achieved, 5 frequency of exchanges gradually. If no resp onse obtained within one week, change FFP replacement to cryosupernatant (rationale: it lac ks high molecular weight multimers of von Willebrand factor postulated in endothelial damag e disease trig- gers). 531 4. Give RBC as necessary but reserve platelet transfusions for severe mucosal or intracrani al bleeding as reports suggest they may worsen the disease. 5. Cover for infection with IV broad spectrum antibiotics including teicoplanin if necessary to preserve the apheresis catheter. 6. Start anticonvulsants if fitting. 7. Most would start high dose steroids (prednisolone 2 mg/kg/d PO) with gastric protection although evidence is equivocal. 8. Aspirin/dipyridamole/heparin may be considered for non-responders. 9. Refractory patient s ( 10%) should be considered for IV vincristine. 10. Still refractory patients may achieve remission with splenectomy. 11. Response to treatment may be dramatic e.g. ventilated, com atose patient watching TV in the afternoon after plasma exchange in the morning! Prognosis 2 90% respond to plasma exchange with FFP replacement. 2 30% will relapse. Most respond again to further plasma exchange but leaves 15% who become chronic relapsers. 2 Role of prophylaxis for chronic relapsers unclear. Intermittent FFP infusions or continuo us low dose aspirin may help individual cases. 13-haem emergencies.qxd 10.12.2003 04.30 PM Page 532 Sickle crisis Management (cid:2) Early and effective treatment of crises essential (hospital). (cid:2) Re st patient and start IV fluids and O2 (patients often dehydrated through poor oral intake of fluid + excessive loss if fever). (cid:2) Start empirical antibiotic therapy (e.g. cephalosporin) if infection is sus- pected whilst culture results (blood, urine or sputum) are awaited. (cid:2) Analgesia usually required \200\224e.g. intravenous opiates (diamorphine/morphine) especially when patients are first admitted to hospital. Switch late r to oral medication after the initial crisis abates. (cid:2) Consider exchange blood trans fusion (if neurological symptoms, stroke or visceral damage). Aim to 5 HbS to <30%. (cid:2) Exchange transfusion if PaO2 <60mm on air ((cid:2)chest syndrome). (cid:2) a-adrene rgic stimulators for priapism. (cid:2) Seek advice of senior hematology staff. (cid:2) Cons ider regular blood transfusion if crises frequent or anemia is severe or patient has had CVA/abnormal brain scan. (cid:2) Top-up transfusion if Hb <4.5g/dL (hunt for cause). Transfusion and splenectomy may be lifesaving in children with splenic sequestration. 532 (cid:27) www.bcshguidelines.com/pdf/SICKLE.V4_0802.pdf 13-haem emergencies.qxd 10.12.2003 04.30 PM Page 533 Hematological emergencies 533 13-haem emergencies.qxd 10.12.2003 04.30 PM Page 534 This page intentionally left blank 534 14-supportive care.qxd 10.12.2003 04.32 PM Page 535 Supportive care 14 Quality of life 536 Pain management 538 Psychological support 540 14-supportive care.qxd 10.12.2003 04.32 PM Page 536 Quality of life In managing any disease problem a key objective is to improve the quality of a patient \200 \231s survival as well as its duration. Part of the clinical decision- making process takes into account quality of life (QoL) in judging the most appropriate treatment. Defining quality of life precisely is not easy; it has been described as a measure of the d ifference at a particular time point between the hopes and expectations of the individual a nd that individual \200\231s present experi- ences. QoL is multifaceted and can only be ass essed by the individual since it takes into account many aspects of that individual \200 \231s life and their current perception of what, for them, is good QoL in their specific ci rcumstances. A clear distinction exists between performance scores (e.g. Karnofsky or WHO) which record functional status and assess independence; these are assessed by the physician according to pre-set criteria. They have erro- neously been considered to be surrogate markers of QoL. Patient QoL as assessed by the treating physician has been shown to be unreliable in an onc ological setting. There is no single determinant of good QoL. A number of qualities which go to make up QoL a re capable of assessment; these include ability to carry on normal physical activities, abi lity to work, to engage in normal social activities, a sense of general well-being and a pe rception of health. Several validated instruments now exist to measure QoL; these mainly involve questionnaires completed by the patient. They are simple to com- plete and involve \200\230yes \200\231 or \200\230no \200\231 answers to specific questions, answers on a linear analog scale or the use of 4- or 7- point Likert scales. 536 Available QoL instruments include 2 Functional Living Index \200\223 Cancer (FLIC)1 2 Func tional Assessment of Cancer Therapy (FACT)2 2 European Organization for Research and Treatm ent in Cancer (EORTC) Quality of Life Questionnaire C-30 (QLQ C30)3 Data from validated QoL questionnaires are now accepted as a require- ment and a clinical e nd point in many major clinical trials, especially in malignancies, particularly those wher e survival differences are minimal between contrasting therapy approaches. Where survivals are minimally affected it is then essential to focus on treatments which will offer the bes t QoL. Schipper, H. et al. (1984) Measuring the quality of life of cancer patients: the Functional Living Index \200\223Cancer: development and validation. J Clin Oncol, 2, 472 \200\223483; Cella, D.F. et al. (1993) The Functional Assessment of Cancer Therapy scale: development a nd validation of the general measure. J Clin Oncol, 11, 570 \200\223579; Aaronson, N.K. et al. (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a qualit y-of-life instrument for use in international clinical trials in oncology. J Natl Cancer In st, 85, 365 \200\223376. 14-supportive care.qxd 10.12.2003 04.32 PM Page 537 Supportive care 537 14-supportive care.qxd 10.12.2003 04.32 PM Page 538 Pain management Pain is a clinical problem in diverse hematological disorders, notably in sickle cell disea se, hemophilia and myeloma. Acknowledgement of the need to manage pain effectively is an es sential part of successful patient care and management in clinical hematology. Pain may be local or generalized. More than one type of pain may be present and causes may be multifactorial. It is most important to listen to the patient and give him/her the chanc e to talk about their pain(s). Not only will this help determine an appropriate therapeutic strategy, the act of listening and allowing the patient to talk about their pains and asso ci- ated anxieties is part of the pain management process. Engaging the patient in \200\230measuring \200\231 their pain is often helpful; it enables specific goals to be set and provides a means to assess the effectiveness of the analgesic strategy. Basic to the control of pain is to manage and remove the pathological process causing pain, wherever this is possible. Analgesia must be part of an integrated care plan which takes t his into account. Analgesic requirements should be recorded regularly as these form a valu- able \200\230sem i-quantitative \200\231 end point of pain measurement. Reduction in requirements, for examp le, is an indicator that attempts to remove or control the underlying cause are succeeding. Managing pain successfully involves patient and family/carer participation, a collaborative multidisciplinary approach in most categories of haematolog- ical disorder related pain; m edication should aim to provide continuous pain relief wherever possible with a minimum of drug related side effects 538 Analgesics Simple non-opioid analgesics Paracetamol: 1g 4 \200\2236 hourly, oral as tablets or liquid; suppositories available. No contraindication in liver disease; useful in mild to moderate pain. Ibuprofen 800mg or dicl ofenac 75 \200\223100mg bd as slow release formulations can be synergistic with other analg esics; combined formulations of diclofenac with misoprostol may reduce risks of gastric irr itation bleeding; useful in combination with paracetamol or weak opioids Dextropropoxyphene 100mg usually combined with paracetamol 1g as coproxamol tablets; usual dosage is 2 tablet s 6 hourly or codeine 30 \200\22360mg or dihy- drocodeine 30 \200\22360mg up to 4 hourly pr ovide effec- tive analgesia for moderate pain. Confusion, drowsiness may be associated with initial usage in some. Weak (and strong) opioids cause constipa- tion; usually requires si mple laxatives Morphine available as liquid or tablets commencing at 5 \200\22310mg and giv en 4 hourly is treatment of choice Anti-inflammatory drugs Weak opioids Strong opioids 14-supportive care.qxd 10.12.2003 04.32 PM Page 539 Supportive care in severe pain. Once daily requirements are estab- lished patients can be \200\230converte d \200\231 to 12 hourly slow release morphine preparations. Breakthrough pain can be treate d with additional doses of 5 \200\22310mg morphine. Diamorphine preferred for parenteral us age. Highly soluble and suitable for use in a syringe driver for continuous administration or as a 4 hourly injection. Tramadol may be given orally. Fentanyl given as slow release tr ansdermal patches may be a valuable alternative to slow release morphine for moderate to se vere chronic pain. Alternatives to opioids For chronic pain give analgesia PO regularly, wherever possible. 2 Pain control is very specific to the individual patient, there is no \200\230correct \200\231 formula other than the combination of measures which alle- viate the pain. 2 The clinician should work \200\230upwards \200\231 or \200\230downwards \200\231 throug h the levels of available analgesics to achieve control. 2 Constipation due to analgesics should be managed with aperients. 2 Nausea or vomiting may occur in up to 50% patients with strong opiates; cyclizine 50mg 8 hourly, metoclopramide 10mg 6 hourly or haloperidol 1.5mg 12 hour ly are available options to limit nausea or vomiting. 2 Additional general measures include \200\223 Radiotherapy for localized cancer pain. \200\223 Physical methods e.g. TENS or c onsideration of nerve root block. \200\223 Surgery, especially in myeloma where stabilizin g fractures and 539 pinning will relieve pain and allow mobility. \200\223 Encouraging/allowing patients to utilize \200\230alternative \200\231 approaches . including relaxation techniques, aromatherapy, hypnosis, etc. 2 Additional drug therapy \200\223 Antidepressants e.g. amitriptyline may help in neuropathic pain. \200\223 Antico nvulsants e.g. carbamazepine may be helpful in neuropathic pains especially in post-herpetic neuralgia. \200\223 Corticosteroids, particularly dexamethasone, to relieve leukaemic bone pain in late stage disease. Many hospitals also run specific pain clinics. The support and expertise available should b e enlisted particularly for difficult problems with persis- tent localized pain e.g. post-h erpetic neuralgia. For long term painful con- ditions it is essential to work with medical and nursing colleagues in Primary Care and in Palliative Care so that the patient receives appro- priate support in the community setting. 14-supportive care.qxd 10.12.2003 04.32 PM Page 540 Psychological support Many hematological disorders are long term conditions; the specific diag- nosis can be seen to \200\230label \200\231 the patient as different or ill and therefore will exert a prof ound influence on their life and that of their immediate family or carers. Patients (and th eir families) experience and demonstrate a number of reactions to their diagnosis, the clin ical hematologist needs to have an awareness of this and respond accordingly. Reactions to serious diagnosis include 2 Numbness. 2 Denial. 2 Anger. 2 Guilt. 2 Depression . 2 Loneliness. Ultimately most patients come to acceptance of their condition; carers/ partners will also go through a similar range of reactions. The clinician needs to be aware of the way in whic h news of a diagnosis is likely to affect a patient and his/her family/carers and respond a ppropriately. In the first instance this will often involve the need to impart the diagnosi s, what it means and what needs to be done clinically. There is no \200\230right way \200 \231 to impart bad or difficult news. It is very important to make and take time to tell th e patient of the diagnosis. Wherever possible this should be done in a quiet, private setti ng. Numbness at learning of a serious diagnosis often means that very little is taken in in itially other than the diagnostic label. The various reactions listed above may subsequentl y emerge during the time the patient comes to accept the diagnosis, what it means and what is to be done clinically. Within the hematological team there should be support available to the patient and family/c arers which can provide them with practical informa- tion about the disease and its managem ent. Simply knowing there is a sym- pathetic ear may be all that is required in the way of support; however, for some patients and families/carers more specialized support may be nee ded e.g. availability of formal counseling or access to psychological or psychiatric suppor t. 540 Use can be made of local or national patient support groups; knowledge of others in similar predicaments can help diffuse anger and loneliness. Support groups can also be a valuable resource in providing information and experience which patients and families/carers find he lpful. The most effective psychological support for hematological patients is to see them as indiv iduals and not \200\230diseases \200\231. 14-supportive care.qxd 10.12.2003 04.32 PM Page 541 Supportive care 541 14-supportive care.qxd 10.12.2003 04.32 PM Page 542 This page intentionally left blank 542 15-protocols.qxd 10.12.2003 04.32 PM Page 543 Protocols and procedures 15 Acute leukemia \200\223 investigation 544 Platelet storage and administration 546 Platelet transfusion support 547 Platelet reactions and re fractoriness 548 Prophyla ctic regimen for neutropenic patients 550 Guidelines for use of IV antibiotics in neutropenic patients 552 Treatment of neutropenic sepsis when source unknown 5 54 Treatment of neutropenic sepsis when source known/suspected 556 Prop hylaxis for patients treated with purine analogs 558 Tu mor lysis syndrome (TLS) 560 Management of chronic bone marrow failure 562 Venepuncture 564 Venesection 566 Tunnele d central venous catheters 568 Bone marrow examination 570 Administration of chemotherapy 572 Antiemetics for chemotherapy 574 Intrathecal chemotherapy 576 Manageme nt of extravasation 578 Specific procedures following extravasation 580 Splenectomy 582 Plasma exchange (plasmapheresis) 584 Leucapheresis 586 Anticoagulation therapy \200\223 heparin 588 Oral anticoagulation 590 Management of needlestick inju ries 592 Chemotherapy p rotocols 594 VAPEC-B 594 ABVD 596 ChlVPP 598 MOPP 600 MOPP/ABVD 602 CHOP 604 R-CHOP 605 DHAP 606 ESHAP 608 Mini-BEAM 610 BEAM (myeloablative conditioning regimen) 612 CVP 614 Fludarabine and cyclophosphamide 616 FMD 618 ABCM 620 C-VAMP 622 VAD 624 Z-DEX 626 C-Thal-Dex (CTD) 628 Note Please check local protocols since these may differ to those outlined in this handbook. 15-protocols.qxd 10.12.2003 04.32 PM Page 544 Acute leukemia \200\223 investigation Hematology 2 FBC, blood movie, reticulocytes, ESR. 2 Serum B12, red cell folate, and ferrit in. 2 Blood group, antibody screen and DAT. 2 Coagulation screen, INR, APTT, fibrinogen (an d XDPs if bleeding). 2 BM aspirate for morphology, cytogenetics, immunophenotype (and peripheral blood if relevant) plus samples required by the MRC trials. 2 BM trephine biopsy. Biochemistry 2 U&E, LFTs. 2 Ca2+, phosphate, random glucose. 2 LDH. 2 Serum and urine lysoz yme (if M4 or M5 AML suspected). Virology 2 Hepatitis BsAg. 2 Hepatitis A antibody. 2 Hepatitis C antibody. 2 HIV I and II a ntibody (counseling and consent required). 2 CMV IgG and IgM. Immunology 2 Serum immunoglobulins. 2 Autoantibody screen profile. 2 HLA type \200\224Class 1 always in case HLA matched platelets are required, Class 1 and 2 if allogeneic transplant indicated. Bacteriology 2 Baseline blood cultures. 2 Throat swab. 2 MSU. 2 Stool for fungal culture. 2 Nose swab for MRSA if transferred from another hospital/unit. 544 Cardiology 2 ECG. 2 Echocardiogram, only if in cardiac failure or infective endocarditis su s- pected or significant cardiac history. Radiology 2 CXR. 2 Sinus radiographs. Other 2 If any evidence of severe dental caries or gum disease refer patient for dental assessment before chemotherapy. 2 Consider semen storage. 15-protocols.qxd 10.12.2003 04.32 PM Page 545 Protocols and procedures 545 15-protocols.qxd 10.12.2003 04.32 PM Page 546 Platelet storage and administration Storage Platelets should be stored at room temperature (20 \200\22322 C) in a platelet agi tator until infused. Helps to retain function. Use before expiry date on pack. 2 Platelet p acks should be inspected before infusion \200\224platelet packs that look visibly pink due to RBC contamination should not be used. \200\223 Occasionally fine fibrinoid strands may be seen in concentrates (give a slightly stringy or cloudy appearance). Such strands disperse with gentle massage a nd are safe to use. \200\223 Occasionally larger aggregates of platelets and/or white cell clumps are seen in the bags which do not disperse with gentle massage. Such bags are dangerous and should neve r be infused. Dosage and timing 2 A single dose of platelets is generally supplied as a single bag. 2 Rep resents a standard transfusion dose although twice this amount may be required to cover insertions of central lines or minor surgery. 2 Occasionally double doses may be required for patients becoming refractory. 2 The frequency of platelet transfusion will be determined by clinical cir- cumstances. In general, a patient who is well, afebrile and with no evi- dence of new bruising or bleeding need only have a platelet count maintained above 10 109/L. May be achieved with platele ts given as infrequently as every 2 \200\2234 days with this estimate being guided on daily platelet counts. 2 Patients who are infected or bleeding have much greater platelet requirements \200\224aim to keep the platelet count >20 109/L. This will usually mean da ily platelet infusions for the duration of this clinical episode. 2 Platelet counts of <10 109/L should always be avoided but within these constraints the fewer platelets transfused the better since this reduces the risk of alloimmunisation to H LA and platelet antigens. 2 Anyone with a persistent platelet count <10 109/L should be started on tranexamic acid 1g qds PO or IV unless specific contraindications exist such as genitourinary tract bleeding. 546 Choice of blood group for platelet support At diagnosis, all patients should have a blood g roup and CMV antibody status determined. Patients should receive platelets of their own blo od group as far as possible. Due to fluctuations in supply, this is not always possible and the choice is less critical than for red cell transfusions as platelet ABO blood group ant igen expression is weak and the recipient is exposed only to donor plasma. 15-protocols.qxd 10.12.2003 04.32 PM Page 547 Protocols and procedures Patient \200\231s blood group first choice second choice O A B AB O A B (if available) A A O A preferably or O O 2 Rh (D) +ve patients may receive Rh (D) +ve or Rh (D) \200\223ve products. 2 Rh (D) \200 \223ve patients should receive Rh (D) \200\223ve platelets. 2 Occasionally necessary to give Rh (D) +ve platelets to Rh (D) \200\223ve patients. The B lood Bank should be informed as all future red cell transfusions must be Rh (D) \200\223ve . Anti-D administration may be given to such patients routinely or may be reserved for wome n of child- bearing age (dose: 250iu (50 g). Anti-D SC immediately after the transfusion. Platelet transfusion support See p546 and p650. 547 15-protocols.qxd 10.12.2003 04.32 PM Page 548 Platelet reactions and refractoriness Reactions to platelet transfusion are common and range from mild tem- peratures to rigors. The development of an urticarial rash is also fre- quently seen. When a transfusion reactio n develops, the following steps should be taken: (cid:2) Stop the transfusion. (cid:2) Give 10mg chlorphenamine (chlorpheniramine) IV and 1g of paracetamol PO. (cid:2) Cover future transfusions with chlorpheniramine and paracetamol 30 mins pre-transfusion. 2 Hydrocortisone 100mg IV stat may be (sparingly) used for refractory reactions 2 Pethidine is a suitable alternative for severe reactions and is almost invariably effective. Give 25mg IV stat with repeat dose if necessary or set up an IVI of 2 5 \200\22350mg IV over 8h. 2 The possibility of generation of HLA and platelet-specific antibodies should also be considered (see below). Platelet refractoriness Occasionally patients show little/no increment in the platelet coun t after platelet transfusions. This is called platelet refractoriness. May be due to physic al or immunological mechanisms in the patient. The commonest physical mechanism is of plate let circulatory half-life reduction caused by concurrent sepsis or coagulopathy e.g. DIC. I mmunological causes include induction of anti-HLA antibodies due to allosensitisation from previous transfusions or generation of anti-platelet antibodies such as in ITP. Investigati on should be considered if platelet transfusions fail to maintain a platelet count >10 1 09/L at all times. Proceed as follows 1. Check FBC pre-platelet infusion, 1 and 12h post-infusion to assess th e rate of platelet count decay. Failure to show a rise of platelet count by at least 10 109/L at 1h or any rise after 12h post-infusion merits further testing. 548 2. Samples should be sent to a blood transfusion center for HLA and platelet antibody scree ning (10mL EDTA samples and 20mL serum). 3. The patient \200\231s own HLA type should be checked. 4. If HLA or platelet antibodies are identified, the provision of HLA or platelet antigen matc hed platelet products may improve the platelet transfusion responsiveness. Platelet refractoriness \200\224More than two-thirds of patients receiving multiple transfu sion with random platelets develop anti-HLA antibodies. Refractoriness defined as failure o f 2 consecutive transfusions to give corrected increment of >7.5 109/L 1h after platelet transfusion in absence of fever, infection, severe bleeding, splenomegaly, or DIC. GvHD \200\224Rare complication where there is engraftment of donor lymphocytes in platelet concentrate in severely immunocompromised patients. 15-protocols.qxd 10.12.2003 04.32 PM Page 549 Protocols and procedures Calculating platelet increment [(P1 \200\223P0) SA]/n P0 = platelet count pre-transfusion ( 109/L) P1 = platelet count post-transfusion ( 109 /L) SA = surface area n = number of units of platelets transfused Corrected increment 60 min after transfusion >7.5 109/L indicates successful platelet tr ansfusion (P1 \200\223P0). 549 Hows, J.M. & Brozovic, R. (1992) in ABC of Transfusion 2nd edn BMJ Publications. 15-protocols.qxd 10.12.2003 04.32 PM Page 550 Prophylactic regimen for neutropenic patients Infective risk is related to the severity and duration of neutropenia. Higher risk immunolo gical defects e.g. hypogammaglobulinaemia in myeloma, T-cell defects e.g. HIV disease, addi tional immunosuppressive agents e.g. cyclosporin post-transplant, and older patients. Princ ipal risk is from bacterial organisms but fungi and viruses, especially herpes (HSV, HZV) a nd CMV are also seen in pro- longed neutropenia. is associated with concurrent Typical protocols include 2 Isolation procedures \200\224strict handwashing by all patient contacts is the only isolation measure of universally proven benefit. Others include visit or restriction, gloves, aprons, gowns, masks and full reverse barrier nursing. Isolation ro oms with positive pressure filtered air will prevent fungal infection. 2 Drinks \200\224avoid mains tap water/still mineral water (use boiled water or sparkling mineral water). Avoid unpasteurised milk and freshly squeezed fruit juice. 2 Food \200\224avoid cream, ice-cream, soft, blue or ripened cheeses, live yogurt, raw eggs or derived foods e.g. mayonnaise and souffl s, cold chicken, meat pat , raw fish/shellfish, unpeeled fresh vegetables/salads, unpeeled fruit, uncooked herbs and sp ices, ground pepper (contains Aspergillus spores). 2 General mouthcare \200\224antiseptic mouthwash e.g. Corsadyl 10mL 4 hourly swish and spit. If soreness develops, substitute Difflam mouth- wash. For discrete o ral ulcers, use topical Adcortyl in Orobase; for generalized ulceration use 0.9% saline mou thwash hourly, swish and spit. Corsodyl toothpaste should replace standard preparations. Or al antifungal prophylaxis should be nystatin susp. 1mL 4 hourly swish and spit or swallow, or amphotericin lozenges one to suck slowly 4 hourly. 2 Antibacterial prophylaxis \200\224 aim to alter flora and prevent exogenous colonization. Principal agents: ciprofloxacin 250m g bd or cotrimoxa- zole 480mg bd or colistin 1.5MU tds and neomycin 500mg qds. All given PO starting 48h after antifungal prophylaxis. 550 2 Antifungal prophylaxis \200\224a systemic imidazole compound is most routinely used e.g. fluconazole 100mg PO od. Itraconazole liquid 2.5mg/kg bd PO may offer additional protectio n against Aspergillus. 2 Antiviral prophylaxis \200\224Acyclovir is the most useful drug a t pre- venting herpes reactivation. Dose is dependent on degree of immuno- suppression and thus th e likely organism to be encountered. 400mg bd will prevent HSV reactivation e.g. post-stand ard chemotherapy; 400mg qds may prevent HZV reactivation e.g. post-SCT; 800mg tds or more m ay prevent CMV reactivation post-allogeneic SCT. 2 Additional prophylaxis for specials situations \200\224history of, or radio- logical evi dence of, tuberculosis (TB). Consideration should be given to standard anti-TB prophylaxis e.g. rimactazid/pyridoxine particularly if prolonged neutropenia expected. Splenectomised p atient \200\224at extra risk from encapsulated organisms particularly Streptococcus pneumo niae, Haemophilus influenzae and Neisseria meningitidis. Use penicillin V 500mg 15-protocols.qxd 10.12.2003 04.32 PM Page 551 Protocols and procedures od PO or erythromycin 250 mg od PO if penicillin allergic as prophy- laxis switching to hig h dose amoxicillin/cefotaxime if febrile. Post-SCT (see p294). 551 15-protocols.qxd 10.12.2003 04.32 PM Page 552 Guidelines for use of IV antibiotics in neutropenic patients Urgent action required if neutropenic patient develops 2 Single fever spike >38 C. 2 2 fev er spikes >37.5 C 1h apart. 2 Symptoms or signs of sepsis even without fever. Assessment 2 Search for localizing symptoms or signs of infection. 2 Full clinical examinat ion noting BP, pulse, mouth, chest, perineum, line sites, skin and fundi. 2 O2 saturation (pulse oximetry). 2 FBC, U&E, creatinine, LFTs, CRP, INR, APTT, fibrinogen. 2 Perform a septic screen: \200\223 3 sets of blood cultures (10mL per bottle optimizes organism recovery) if central line present, take paired peripheral and central samples. \200\223 Single further blood culture set if non-response at 48 \200\22372h or con- dition changes. 2 Swab relevant sites: wounds, central line exit site, throat. 2 Sputum culture. 2 MSSU. 2 Feces if symptomatic incl. C difficile toxin. 2 Viral serology if clinically relevant. 2 CX R. 2 Other imaging as relevant, consider sinus x-ray. 2 Consider bronchoalveolar lavage if chest infiltrates present. 2 Consider risk of invasive fungal infection: CT chest if high r isk. Empirical treatment Start IV antibiotics to provide broad spectrum cover. Stop prophylactic ciprofloxacin. Follow local protocol if available. 552 First line: Tazocin 4.5g tds plus gentamicin 6mg/kg/day. If patient has history of penicillin allergy use ceftazidime 2g tds instead of tazocin; if anaphylaxis with penicillin discuss with microbiologist. If suspected line infection (exit site inflammation) add vancomycin 1g bd and consider line removal. Vancomycin dose should be split and adminis- tered through each lumen. May be loc ked in the line for 1h then flushed. If there are signs of perianal sepsis, mucositis or intra-abdominal infection or if C diffi cile is suspected add metronidazole 500mg tds IV. 1. Patients on od gentamicin should have pre-dose level checked 24h after first dose then twice weekly if satisfactory. 2. Patients on vancomycin should have pre-dose levels checked immedi- ately before 3rd or 4 th dose (2nd if renal impairment) then twice weekly if satisfactory. 15-protocols.qxd 10.12.2003 04.32 PM Page 553 Protocols and procedures Reassess at 48 \200\22372h: If no response to antibiotics and negative blood cultures: Add vancomycin 1g bd. If already on vancomycin, consider line removal. Consider risk of invasiv e fungal infection. CT chest if high risk. Reassess after further 48 \200\22372h: If no response to antibiotics and negative blood cul tures: If high risk for invasive fungal infection: Stop above antibiotics. Commence amphotericin 1 mg/kg/day plus ciproflo- xacin 500mg bd PO/IV. Stop prophylactic fluconazole/itraconazole. If low risk for invasive fungal infection: Switch antibiotics to meropenem 1g tds plus gent amicin 6mg/kg/day. Reassess after further 48h: If no response to amphotericin, change ciprofloxacin to meropen em 1g tds plus gentamicin 6mg/kg/day. If not on amphotericin, consider switching to amphotericin 1mg/kg/day plus ciprofloxacin 50 0mg bd PO/IV. Stop prophylactic fluconazole/itra- conazole. Duration of therapy If temperature responds but cultures are negative, continue anti-infect ive treatment until apyrexial for 72h or minimum 5d course. If still neu- tropenic restart prophylactic anti-infectives. Amphotericin should be con- tinued until neutrophil regenerat ion or total dose of 1g administered. Positive cultures Antibiotic therapy may be changed on the basis of positive cultures. 553 15-protocols.qxd 10.12.2003 04.32 PM Page 554 Treatment of neutropenic sepsis when source unknown (cid:2)(cid:2) One of the commonest haemato-oncological emergencies. 2 May be defined as th e presence of symptoms or signs of infection in a patient with an absolute neutrophil count of <1.0 109/L. In practice, the neutrophil count is often <0.1 109/L. 2 Similar clinical picture also seen in neutrophil function disorders such as MDS despite normal neutrophil numbers. 2 Beware \200\224can occur without pyrexia, especially patients on steroids. Immediate action (cid:2)(cid:2) Urgent clinical assessment. 2 Follow ALS guidelines if card iorespiratory arrest (rare). 2 More commonly, clinical picture is more like cardiovascular shock respiratory embarrassment viz: tachycardia, hypotension, peripheral vasodilatation and tachypnoea. Occurs with both Gram +ve (now more common with indwelling central cathete rs) and Gram \200\223ve organ- isms (less common but more fulminant). 2 Immediate rapid infusion of albumin 4.5% or gelofusin to restore BP. 2 Insert central cat heter if not in situ and monitor CVP. 2 Start O2 by face mask if pulse oximetry shows satur ations <95% (common) and consider arterial blood gas measurement \200\224care with platelet counts <20 109/L \200\224manual pressure over puncture site for 30 mins. 2 Perform full septic screen (see p552). 2 Give the first dose of first line antibiotics im mediately e.g ureidopeni- cillin and loading dose aminoglycoside (ceftazidime or ciprofloxa cin if pre-existing renal impairment). Follow established protocols. 2 If the event occurs while patient on first line antibiotics, vancomycin/ ciprofloxacin or vancomycin/meropenem are suitable alternatives. 2 Commence full ITU-type monitoring chart. 2 Monitor urine output with urinary catheter if necessary \200\224if renal shut- down has already occurred, give single bolus of IV frusem ide. If no response, start renal dose dopamine. 554 2 If BP not restored with colloid despite elevated CVP, consider inotropes. 2 If O2 saturations remain low despite 60% O2 delivered by rebreathing mask, consider ventilation. 2 Alert ITU giving details of current status. Subsequent actions 2 Discuss with senior colleague. 2 Amend antibiotics according to cultur e results or to suit likely source if cultures negative. 2 Check aminoglycoside trough levels after loading dose and before second dose as renal imp airment may determine reducing or with- holding next dose. Consider switch to non-nephrotox ic cover e.g. cef- tazidime/ciprofloxacin. 2 Continue antibiotics for 7 \200\22310d minimum and usually until neutrophil recovery. 15-protocols.qxd 10.12.2003 04.32 PM Page 555 Protocols and procedures 2 If cultures show central line to be source of sepsis, remove immedi- ately if patient not responding. 555 15-protocols.qxd 10.12.2003 04.32 PM Page 556 Treatment of neutropenic sepsis when source known/suspected Central indwelling catheters Very common. Organisms usually Staph. epidermidis but can be o ther Staph spp. and even Gram \200\223ve organisms. May be erythema/exudate around entry o r exit sites of line, tenderness/erythema over subcutaneous tunnel or discomfort over line tract. Blood cultures must be taken from each lumen and peripherally and labeled individual ly. Add vancomycin 1g bd IV if not in standard protocol. Split dose between all lumens unle ss cultures known to be +ve in one lumen only. Lock and leave in line for 1h, then flush th rough. If no response or clinical deterioration, remove line imme- diately. Perianal or periodontal Both are common sites of infection in neutropenic patients. Periana l lesions may become secondarily infected if skin abraded. Add metronida- zole 500mg IV tds to standard therapy. Painful SC abscesses may form and may require surgical incision. Gum disease and localized tooth infec- tions/abscesses are frequently seen. Add metronidazole t o therapy as above, arrange OPG and dental review as surgical intervention may be required in non-responders. If possible, best delayed until neutrophil recovery in most cases \200 \224then do electively before next course of chemotherapy. Lung Atypical organisms