Clinical Guideline. Guideline for the use of human albumin solution (HAS)

Transcription

1 Clinical Guideline Guideline for the use of human albumin solution (HAS) Guideline Summary This document outlines the indications for the use of human albumin solution in adult and paediatric patients at Guy s and St. Thomas NHS Foundation Trust. Document Detail Document Type Guideline Document name Guideline for the use of human albumin solution (HAS) Document location Gti Version 1.0 Effective from May 2015 Review date May 2017 Owner Hospital Transfusion Committee Authors Dr Andrew Retter Dr Susan Robinson Dr Michael Robson Dr Christopher Reid Dr Paul Holmes Dr Toby Garrood Approved by, date Keywords Albumin, HAS, ECMO, sepsis, critical care, renal, liver, neurology, plasma exchange Relevant external law, NA regulation, standards 1

2 INDEX 1.0 Introduction Background and rationale for use 4 Modified ASFA Guideline Indications for PEX Categories 3.0 Demand management and ordering 7 HAS Demand management colour coding and definition Human Albumin Solution Assessment Panel designated speciality consultant Demand management programme 4.0 Prescribing, Consent, Traceability Potential risks Guidance for the use of 20% HAS Guidance for the use of 4.5% and 5% HAS Plasma Exchange References Appendices Modified ASFA 2013 Indication Categories for Plasma Exchange with 4.5% or 5% HAS within service provision GSTT Modified AFSA Category IV relevant to this guidance Human albumin solution assessment panel terms of reference KEY POINTS: This document Provides guidance on HAS indications and contraindications. Provides guidance on the Trust HAS demand management programme. Provides guidance how to request HAS. 2

3 1.0 Introduction Human albumin solution (HAS) is widely used in clinical practice. However, there is no formal guidance governing its use in the UK and in many clinical situations there is a limited evidence base and a number of alternatives exist. The widespread use of HAS, combined with restrictions on the use of UK derived plasma following concerns over possible transmission of nvcjd and production issues have led to high cost and shortages. Currently the UK faces an acute shortage in the supply of 4.5% HAS and potentially 20% HAS. This document provides clinical guidance to clinicians regarding the HAS indications and contraindication and details the Trust demand management programme and how to request HAS. The demand management programme aims to ensure usage is restricted to the most appropriate indications and alternatives considered where possible to ensure adequate stocks remain of this finite blood product. The demand management programme will be revised if shortages worsen or the Department of Health implement a demand management programme which differs. This document will also serve as a reference point to facilitate future audit. The guideline should be used by all staff involved in issuing, prescribing, consenting and administering HAS. 3

4 2.0 Background and rationale for use. HAS preparations are traditionally available in 4.5% and 20% preparations and in view of the recent shortage a 5% preparation will also become more available. The 4.5% and 20% preparations are very different in their scope and should not be used interchangeably. The 4.5% solution has the same oncotic pressure as plasma and its uses are quite different from the hyperoncotic 20% solution. The benefits of HAS are controversial, proponents argue that in addition to maintaining plasma oncotic pressure that HAS has a number of secondary functions which might be beneficial. These secondary functions include an anti-oxidant potential, endothelial stabilisation, an anti-inflammatory effect and the binding and transport of numerous plasma constituents and drug. However, two Cochrane reviews published in 1998 and updated in 2011 concluded that there was no evidence that HAS reduces mortality when compared to cheaper alternatives such as saline (1, 2). The largest study evaluating the clinical use of HAS was the SAFE study (3). The overall conclusion of the study was that resuscitation with HAS or normal saline resulted in similar outcomes at 28 days. However, additional analyses of the SAFE data yielded interesting data in two specific subgroups. Firstly resuscitation with HAS was associated with a significantly increased rate of death at 2 years in patients who had suffered a traumatic brain injury (relative risk, 1.63; 95% CI 1.17 to 2.26; P=0.003). In the subgroup of patients with severe sepsis, the relative risk of death among those randomly assigned to receive HAS as opposed to saline was 0.87 compared to 1.05 (95% CI 0.74 to 1.02; p=0.09). The recent ALBIOS study specifically examined the use of HAS in patients with severe sepsis. The trial showed that the use of 20% HAS in the first 7 days of an ITU admission was associated with a higher mean arterial pressure (P=0.03) and a lower net fluid balance (P=<0.001) but there was no significant difference in overall survival (4). Over the last 3 years there has been a 50% increase in the use of HAS nationally. Use has increased in light of a number of studies demonstrating negative outcomes with the use of colloids. The 6S trial revealed an increased mortality rate at 90 days with 6% hydroxyethyl starch compared to Ringer s acetate (5). These findings were corroborated by the CHEST study, which was conducted in 7000 critically ill patients. CHEST showed no difference in overall mortality but there was an increased need for renal replacement therapy and an increased incidence of renal failure (6). As a result of these studies there was a change in the surviving sepsis guidelines and a high level (grade 1B) recommendation was made recommending against the use of hydroxyethyl starch for fluid resuscitation in severe sepsis and septic shock. Although no definitive data is yet available it is the belief of a number of opinion leaders that these studies and the change in surviving sepsis guidelines has resulted in the increased use of HAS. 4

5 20% HAS has an established role in patients with ascites who require large volume paracentesis, develop hepatorenal syndrome or have spontaneous bacterial peritionitis. It is also used in some paediatric patients with nephrotic syndrome (7, 8). An area in which considerable amounts of 4.5 % and 5% HAS are used is apheresis, specifically plasma exchange (PEX). The main indications for plasma exchange, with associated published evidence, are well set out in the American Society for Apheresis (ASFA) (9) American Academy of Neurology (AAN(10)) (11) and Kidney Disease Improving Global Outcomes (KDIGO) and the British Committee for Standards in Haematology (BCSH) guidelines (12). ASFA produces regularly updated evidence-based guidelines. The 2013 ASFA guidelines detail indications for apheresis including plasma exchange (PEX) in categories I-IV (Table 1) and use the Grading Recommendations Assessment, Development and Evaluation (GRADE) system for grading evidence (9). These categories have been modified and incorporated into the Trust HAS demand management plan. Designated speciality consultants have been contacted to confirm usage within Guy s and St Thomas NHS Foundation Trust (GSTT) including the Evelina London Children s Hospital. The indications for PEX relevant to these services that usually require volume replacement with 4.5% or 5% HAS are included in appendix 1 with category and grade of evidence. Indications, which are currently outside of these services have been excluded to simplify this document. Category IV clinical conditions are detailed separately in appendix 2. Table 1. Modified ASFA Guideline Indications for PEX Categories Category I Disorders for which apheresis is accepted as first-line therapy, either as a primary standalone treatment or in conjunction with other modes of treatment. Category II Disorders for which apheresis is accepted as second line therapy, either as a standalone treatment or in conjunction with other modes of treatment. Category III Optimum role of apheresis therapy is not established. Category IV Disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful. In general PEX should be considered for first line treatment of Category I indications and second line treatment of Category II indications. Category III indications should be 5

6 considered on a case-by-case basis or within a trial setting. Category IV is a list of clinical conditions where PEX is not appropriate. The volume, frequency and total number of PEX s needs to be a consultant based decision in keeping with current guidelines (9, 11, 12) Where no national guidance is available for a specific indication, Trust guidelines need to be developed and circulated to the HASAP prior to directorate Clinical Guideline Group and Drugs and Therapeutics Committee (DTC) approval. According to the British Committee for Standards in Haematology (BCSH) Apheresis guidance (12). Except for Thrombotic Thrombocytopenic Purpura (TTP) and related thrombotic microangiopathies in which Solvent Detergent-Fresh Frozen Plasma must be used as the sole replacement fluid for plasma exchange (13), 4.5% to 5% HAS Solution is the most widely used replacement fluid for plasma exchange in the UK (UK Transfusion Services, unpublished data) and also worldwide (14). In contrast to crystalloids such as 0.9% normal saline, HAS maintains the patient s whole blood viscosity and physiological HAS levels. Some centres also use crystalloid solutions as partial replacement fluid for plasma exchange, to reduce cost and minimise blood product exposure, but there is a lack of published data to demonstrate equivalent safety to HAS, and the incidence of vasovagal faints may be increased (15). Whilst this guideline provides a demand management plan for HAS including the use of HAS volume replacement for PEX volume replacement, it does not reference or provide guidance with regards to PEX and replacement fluid in Thrombotic Thrombocytopenic Purpura (TTP) and related thrombotic microangiopathies in which Solvent Detergent-Fresh Frozen Plasma (Octoplas) must be used as the sole replacement fluid for PEX. Further Guidance specific to apheresis and the apheresis service and TTP is available separately on the Trust intranet 6

7 3.0 Demand management and ordering HAS In view of national shortages and increasing use of HAS a demand management programme has been introduced within the Trust and will be implemented and managed by the Human Albumin Solution Assessment Panel (HASAP) (Appendix 3 - terms and references HASAP) chaired by the clinical lead for transfusion. These local guidelines, define usage indications according to a colour code or modified ASFA PEX Category to enable demand management (Table 2), the HASAP designated speciality consultants (Table 3) and provide a 3 stage plan regarding requests, authorisation and use of albumin during times of normal supply, shortage and severe shortage albeit local or national (Table 4). Following notification of a national or local change in supply level a clinical alert and consultant communication will be sent out by the chair or a HASAP member and a further alert will be issued when supply level returns to normal. At all times HAS usage must be a consultant based decision. Whether supplies are normal or a shortage is identified the responsible consultant should discuss all usage, except red indications or category I PEX, with the HASAP designated speciality consultant between 09:00 17:00 who may authorise requests. Grey indications or category III PEX will require approval by two HASAP designated speciality consultants and will be coordinated by the HASAP designated speciality consultant. During any shortage no grey indication or Category III PEX will be authorised. During a severe shortage HASAP will meet virtually following notification and plan to manage all albumin requests case-by-case, all requests will require agreement of 2 HASAP members and will be coordinated by the HASAP designated speciality consultant. When HAS is requested between 17:00-09:00 (out of hours) and supplies are normal or a shortage is identified the responsible consultants must follow this guidance and request retrospective authorisation for all usage except red indications or category I PEX. When a decision to use HAS is made out of hours whether supplies are normal or a shortage is identified HAS will only be made available for red or blue indications or category I PEX. 7

8 Table 2 HAS Demand management colour coding and definition Red: Treatment is considered the highest priority because of a risk to life without treatment. Automatic approval. Blue: A condition where there is a reasonable evidence base but other treatment options are available. Where appropriate other alternative therapies should be used. Approval by HASAP designated speciality consultant. Grey: Conditions where the evidence base is weak. Treatment should be considered on a case-by-case basis. HAS usage should be prioritised to red and blue indications. Approval requires two HASAP designated speciality consultants, which will be coordinated by the HASAP designated speciality consultant. Black: Evidence suggests that the use of HAS is not an appropriate treatment and is not recommended. Table 3 Human Albumin Solution Assessment Panel designated speciality consultant - Renal Dr Michael Robson - Intensive care unit Dr Andrew Retter - Neurology Dr Paul Holmes - Rheumatology- Dr Toby Garrood - Evelina London Children s Hospital Dr Christopher Reid - All other Dr Susan Robinson When supplies are normal or a shortage is identified for PEX indications where 4.5% or 5% HAS is the volume replacement of choice, the responsible consultant will be required to discuss the indication for PEX with the HASAP designated speciality consultant except category I indications. Category II authorisation will require evidence of failed first line treatment, category III will require agreement of two HASAP designated speciality consultants which will be coordinated by the HASAP designated speciality consultant. Category IV lists disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful and will not be authorised. For unlisted conditions where removal of a pathogenic antibody makes biological sense providing there is no published evidence that plasma exchange is ineffective or detrimental in the condition in question will be treated as category III. During a shortage no authorisation of albumin for Category III PEX will be given. During a severe shortage HASAP will meet virtually following notification and plan to 8

9 manage all albumin requests case-by-case, all requests will require agreement of 2 HASAP members and will be coordinated by the HASAP designated speciality consultant. If no albumin is made available for PEX the responsible consultant and apheresis team will need to consider alternative volume replacement. At present the Trust has made a decision not to dilute 20% albumin, however it is noted that some preparations include instruction in the SPC re dilution to achieve a 4.5 or 5% solution. Prior to contacting the blood bank to request HAS an EPR request must be completed which includes details of authorising consultant and enables review of Trust usage Figure 1 (to go live ). Once this EPR request has been completed the requesting clinician must telephone the blood bank and verify the order. The Biomedical Scientist (BMS) will review the order and issue the HAS. The BMS will not be able to issue HAS if the details of the form are incomplete. Between 09:00-17:00 Monday to Friday all requests require detail of the authorising HASAP consultant excluding red or category I PEX. Outside of these times the requestor must chose the drop down out of hours-retrospective authorisation required. A regular report (frequency to be determined according to shortage) will enable the HASAP to review HAS issued. Where retrospective authorisation is required this report will enable confirmation retrospective consent has been obtained via the HASAP designated speciality consultants. 9

10 Table 4. Demand management programme Supply Red Category I Blue Category II Grey Category III Black/Category IV Normal Request 24/7* Request 24/7* Request 24/7* Only request Only request Only request DO NOT USE 09:00-17:00 09:00-17:00 09:00-17:00 Automatic authorisation Automatic authorisation HASAP Authorisation Required** HASAP Authorisation Required HASAP Authorisation Required *** HASAP Authorisation Required *** Shortage Request 24/7* Request 24/7* Request 24/7* Only request 09:00-17:00 DO NOT USE DO NOT USE DO NOT USE Automatic authorisation Automatic authorisation HASAP Authorisation Required** HASAP Authorisation Required Severe Shortage HASAP Authorisation Required *** HASAP Authorisation Required *** HASAP Authorisation Required *** HASAP Authorisation Required *** DO NOT USE DO NOT USE DO NOT USE * The trust will endeavour to enable albumin to be made available 24/7 for these indications ** Between the hours of 17:00-09:00 Retrospective authorisation is required *** 2 HASAP members must authorise 10

11 Figure 1.EPR Screen Shot-EPR tool in progress planned to go live at present seek authorisation according to guidance and clinical alert and contact blood bank to request albumin 11

12 4.0 Prescribing, Consent, Traceability HAS is issued by the Trust blood bank. Similar to other plasma products it is produced by the fractionation of donated whole blood. As HAS is a blood product it must be prescribed for a specific patient and is subject to the same scrutiny and reporting mechanisms as other plasma products including traceability. Consent from the patient must be obtained prior to administration. It is important to remember that patients, who refuse blood products, may decline treatment. 5.0 Potential risks Blood products are inherently very safe in the UK, however, specific risks associated with the use of HAS include: 1. Circulatory overload 2. Infusion/allergic reactions 3. Theoretical risk of transmission of nvcjd 12

13 6. Table 5 Indications for the Administration of 20% HAS Intensive Care Indications for the administration of 20% HAS Indication Details Dose References Acute lung injury and severe respiratory failure Should be used in conjunction with frusemide or another strategy to control fluid balance such as renal replacement therapy. Clear fluid balance goals MUST be charted in electronic ITU patient record (Phillips IntelliSpace CCA ). Severe sepsis and septic shock NOT routinely used Maybe used in patients with refractory septic shock who have received resuscitation with crystalloid and require >0.2mcg/kg/min of norepinephrine to 200mls 20% HAS transfused over 30 to 60mins to target serum albumin concentration >25g/l* - Adult doses NOT routinely used to 200mls 20% HAS transfused over 30 to 60mins - Adult doses - Martin (16) - Martin (17) - ALBIOS Study (4) and 2011 Cochrane reviews (1, 2) - Surviving Sepsis Campign Guideline (18) - ALBIOS Study (4) and 2011 Cochrane reviews (1, 2) - VAST study (19) Volume resuscitation for hypovolaemia or weaning from mechanical ventilation NOT routinely used - Maybe used in patients with gross fluid overload and on low dose inotropes to facilitate weaning from organ supportive therapy. NOT routinely used to 200mls 20% HAS transfused over 30 to 60mins - Adult doses Liver disease Indications for the administration of 20% HAS Indication Details Dose References Hepatorenal syndrome Eligible for liver transplantation in conjunction with vasoactive drugs Day 1: 1g/kg Day 2-14: 0.5g/kg - Sanyal (20) - Gluud (21) The transfusions should stopped once patient s condition has resolved and 2011 Cochrane reviews (1, 2) - ALBIOS Study (4) 13

14 Liver disease (cont.) Indications for the administration of 20% HAS Indication Details Dose References Spontaneous bacterial peritonitis - - Day 1 and 2: 1.5g/kg Day 3 onwards: 1g/kg Paracentesis Please see trust guideline: Management of ascites in cirrhosis for further information. All patients in conjunction with appropriate antibiotics to be used as per GSTT antimicrobial guidance Should be given for all paracentesis. Particularly in critical care consideration should be given to using terlipressin. Oral midodrine may be appropriate on rare occasions. - until significant improvement in the patients clinical condition - 100mls of 20% HAS should be given for every 3L of ascites drained. - Nazaret (22) - Sort (23) - Fernandez (24) - Lata (25) Paediatric kidney disease Indications for the administration of 20% HAS Indication Details Dose References Childhood nephrotic syndrome Children with a) severe refractory oedema; under supervision of consultant paediatric nephrologist b) symptoms and signs of sub-acute intravascular volume depletion, including oliguria, poor peripheral perfusion, abdominal pain, raised creatinine and haematocrit; under supervision of consultant paediatric nephrologist Tables adapted from Ontario Regional Blood Coordinating Network - 1g/kg over 6 hours, with or without frusemide depending on clinical indication and assessment during 20% HAS infusion - Haws (26) - British Association on Paediatric Nephrology Consensus Statement (27) 14

15 7. Table 6: Indications for the use of 4.5% or 5% HAS solution Intensive Care Indications for the administration of 4.5% or 5% HAS Indication Details Suggested dose References Burns/thermal injuries Usually for burns greater than 50% Body Surface Area (BSA). Consideration must be made to transfer the patient to a burn centre in this scenario Should not be routinely used - use to be determined by a consultant intensivist. Volume resuscitation in hypovolaemia NOT routinely used and MAY produce harm in the critically ill Should not be routinely used - SOAP Study (28) - SAFE Study (3) and 2011 Cochrane reviews (1, 2) Traumatic brain injury Evidence suggest patient harm Do not use evidence suggests harm Plasma Exchange use 4.5% or 5% HAS only Renal, Rheumatology, Neurology, respiratory.. Decision to PEX must be a consultant decision Risk assess individual case and consider a 1:2 0.9% saline: 4.5% or 5% HAS volume replacement - SAFE Study (3) 15

16 8.0 Plasma exchange (PEX) 4.5% to 5% HAS Solution (HAS) is the most widely used replacement fluid for PEX. Some centres use crystalloid solutions as partial replacement fluid for plasma exchange, to reduce cost and minimise blood product exposure, but there is a lack of published data to demonstrate equivalent safety to HAS. When commencing PEX the responsible consultant should risk assess whether a 1:2 (0.9% saline: 4.5% or 5% HAS volume replacement) instead of only 4.5% or 5% HAS alone is acceptable based upon the clinical indication and clinical risk factors with regards to maintaining intravascular volume. Any incidents related to the use of 0.9 % saline need to be reported via the Trust incident reporting system. Coagulation parameters should be maintained according to the table 7 below. Table 7. Coagulation and full blood count parameter s regarding PEX Group 1 pts with low risk of bleeding Group 2 - pts with a high risk of bleeding e.g. renal biopsy with in 48hrs Group 3 - pts with active haemorrhage e.g. haemoptysis Target INR and APTTr <1.5 Target INR and APTTr <1.3 Target INR and APTTr <1.3 Target Fibrinogen >1g/l Target Fibrinogen >1.5g/l Target Fibrinogen >1.5g/l Target Platelets >25x10 9 /l Target Platelets >75x10 9 /l Target Platelets >75x10 9 /l Group 1 patients with a low risk of bleeding Coagulation including a Clauss fibrinogen and full blood count (FBC) should be checked 4hrs before each plasma exchange, ideally early in the morning before the planned PEX. IF the INR or APTTr are >1.5 15ml/kg of SDFFP (Octaplas) should be given at the end of the exchange as part of the exchange fluid. If the fibrinogen concentration is <1g/l 2 pools of cryoprecipitate should be given at the end of the exchange. IF the INR or APTTr are >3 or platelet <10x10 9 /l these should be corrected prior to commencing the plasma exchange in discussion with the transfusion consultant. 16

17 Group 2 patients with a high risk of bleeding within the last 48 hours e.g. patients with renal biopsy. As a minimum 15ml/kg SDFFP (Octaplas) should be given at the end of the first and each subsequent PEX as part of the exchange fluid. This is because coagulation becomes predictably prolonged with the first PEX though this partially resolves at 4 hours. The coagulation profile should be checked at the end of the procedure and a further 15ml/kg SDFFP (Octaplas) should be given if the INR or APTTr is >1.3. If the fibrinogen concentration is <1.5g/l 2 pools of cryoprecipitate should be given. Transfusion of platelets maybe required to maintain the platelet count >75x10 9 /l. Group 3 - Patients with active haemorrhage e.g. pulmonary haemorrhage or diffuse alveolar damage SDFFP (Octaplas) should be used for PEX during active haemorrhage. There is a significant risk of exacerbating pulmonary haemorrhage when HAS is used alone. When the patient s condition has improved and there is no further active haemorrhage a clinical decision should be made by the responsible consultant for the patient with regards to switching to PEX with saline/ HAS or to stopping PEX. 17

18 References: 1. Cochrane Injuries Group Albumin R. Human albumin administration in critically ill patients: systematic review of randomised controlled trials. BMJ. 1998;317(7153): Roberts I, Blackhall K, Alderson P, Bunn F, Schierhout G. Human albumin solution for resuscitation and volume expansion in critically ill patients. Cochrane Database Syst Rev. 2011(11):CD Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R, et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350(22): Caironi P, Tognoni G, Gattinoni L. Albumin replacement in severe sepsis or septic shock. N Engl J Med. 2014;371(1): Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Aneman A, et al. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med. 2012;367(2): Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med. 2012;367(20): Rodriguez E, Elia C, Sola E, Barreto R, Graupera I, Andrealli A, et al. Terlipressin and albumin for type-1 hepatorenal syndrome associated with sepsis. J Hepatol. 2014;60(5): Uriz J, Gines P, Cardenas A, Sort P, Jimenez W, Salmeron JM, et al. Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal syndrome. J Hepatol. 2000;33(1): Schwartz J, Winters JL, Padmanabhan A, Balogun RA, Delaney M, Linenberger ML, et al. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: the sixth special issue. J Clin Apher. 2013;28(3): Kidnet Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical practice Guideline for Glomerulonephritis. Kidney Inter., Suppl. 2012; 2: Cortese I, Chaudhry V, So YT, Cantor F, Cornblath DR, Rae-Grant A. Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2011;76(3): Howell C, Douglas K, Cho G, El-Ghariani K, Taylor P, Potok D, et al. Guideline on the use of apheresis procedures for the treatment of patients and the collection of cellular therapy products. wwwbcshguidelinescom/documents/therapeuticapheresisguidelinefinalversionapril Scully M, Hunt BJ, Benjamin S, Liesner R, Rose P, Peyvandi F, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158(3): Weinstein R. Evidence-based apheresis makes the GRADE. J Clin Apher. 2010;25(3): Shemin D, Briggs D, Greenan M. Complications of therapeutic plasma exchange: a prospective study of 1,727 procedures. J Clin Apher. 2007;22(5): Martin GS, Mangialardi RJ, Wheeler AP, Dupont WD, Morris JA, Bernard GR. Albumin and furosemide therapy in hypoproteinemic patients with acute lung injury. Crit Care Med. 2002;30(10): Martin GS, Moss M, Wheeler AP, Mealer M, Morris JA, Bernard GR. A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury. Crit Care Med. 2005;33(8): Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, Intensive Care Med. 2013;39(2):

19 19. Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358(9): Sanyal AJ, Boyer T, Garcia-Tsao G, Regenstein F, Rossaro L, Appenrodt B, et al. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology. 2008;134(5): Gluud LL, Christensen K, Christensen E, Krag A. Systematic review of randomized trials on vasoconstrictor drugs for hepatorenal syndrome. Hepatology. 2010;51(2): Nazaret S, Assade F, Brothier E, Freydiere AM, Bellon G, Cournoyer B. RISA-HPLC analysis of lung bacterial colonizers of cystic fibrosis children. J Microbiol Methods. 2009;76(1): Sort P, Navasa M, Arroyo V, Aldeguer X, Planas R, Ruiz-del-Arbol L, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med. 1999;341(6): Terra C, Guevara M, Torre A, Gilabert R, Fernandez J, Martin-Llahi M, et al. Renal failure in patients with cirrhosis and sepsis unrelated to spontaneous bacterial peritonitis: value of MELD score. Gastroenterology. 2005;129(6): Lata J, Marecek Z, Fejfar T, Zdenek P, Bruha R, Safka V, et al. The efficacy of terlipressin in comparison with albumin in the prevention of circulatory changes after the paracentesis of tense ascites--a randomized multicentric study. Hepatogastroenterology. 2007;54(79): Haws RM, Baum M. Efficacy of albumin and diuretic therapy in children with nephrotic syndrome. Pediatrics. 1993;91(6): Consensus statement on management and audit potential for steroid responsive nephrotic syndrome. Report of a Workshop by the British Association for Paediatric Nephrology and Research Unit, Royal College of Physicians. Arch Dis Child. 1994;70(2): Vincent JL, Sakr Y, Reinhart K, Sprung CL, Gerlach H, Ranieri VM, et al. Is albumin administration in the acutely ill associated with increased mortality? Results of the SOAP study. Crit Care. 2005;9(6):R

20 Appendix 1: Modified ASFA 2013 Indication Categories for Plasma Exchange with 4.5% or 5% HAS within service provision GSTT Disease Name Category Grade Acute disseminated encephalomyelitis II 2C Guillain Barre Syndrome (Acute inflammatory demyelinating polyneuropathy) ANCA-associated vasculitis (Severe) I 1A-2C Anti-glomerular basement membrane disease I 1C-2B Catastrophic Antiphospholipid syndrome II 2C Chronic focal encephalitis (Rasmussen Encephalitis) Chronic inflammatory demyelinating polyradiculoneuropathy Cryoglobulinaemia I 2A Focal segmental glomerulosclerosis I recurrent in transplanted kidney 1B Henoch-Schonlein purpura II 2C Hypertriglyceride pancreatitis III 2C Hyperviscosity in monoclonal gammopathy I 1B-C Immunoglobulin A nephropathy II 2B-2C Lambert-Eaton myasthenic syndrome II 2C Multiple Sclerosis III 1B Myasthenia gravis II 1B Neuromyelitis optica (Devic s syndrome) II 1B Paraneoplastic neurological syndromes II 2C Paraproteinemic demyelinating polyneuropathies II III II I IgG/IgA/IgM III multiple myeloma PANDAS; Sydenham s chorea II 1B Phytanic acid storage disease (Refsum s disease) Renal Transplant Desensitisation (ABOi/ HLAi) I 1B Renal Transplant Humoral Rejection I 1B Stiff person syndrome II 2B Systemic Lupus Erythmatosis-severe II 2C Autoimmune encephalitis II 1C II II 1A 2C 1B 1B-1C 2C 2C 2C 20

21 Appendix 2 Modified AFSA Category IV relevant to this guidance Disease name Amyloidosis, systemic Amyotrophic lateral sclerosis Coagulation factor inhibitors (alloantibody) Dermatomyositis and polymyositis Immune thrombocytopenia Inclusion body myositis POEMS syndrome Psoriasis Renal transplantation ABO incompatible Group A2/A2B into B deceased donor Schizophrenia Systemic lupus erythematosus nephritis 21

22 Appendix 3 Human Albumin Solution Assessment Panel (HASAP) terms of reference At GSTT the HASAP will report to the Drug and Therapeutics Committee and will be a virtual panel, meeting annually unless conditions of shortage are severe or a meeting is called by the chair. 1. Establish and embed local policy The committee is responsible for: 1.1 Establishing and reviewing the Demand Management Plan within GSTT. 1.2 Actively promoting the implementation of guidelines for the appropriate use of HAS. 1.3 Ensuring that hospital guidelines for the use of HAS are up to date and reviewed on a regular basis. 1.4 Ensuring the ability of up to date information about HAS, alternatives and any potential shortages. 1.5 Developing a robust mechanism for informing users when shortages of HAS occur. 1.6 Ensuring the Trust is compliant with NHS England and Department of Health requirements. 2. Approve applications for use of HAS 2.1 Review and consider approving applications for HAS 3. Respond to shortage situations 3.1 During shortages of HAS the committee is responsible for reviewing the availability and local applications to try to ensure that sufficient HAS is available for patients with Red indications and Category I PEX. 3.2 To ensure that the views and requirements of the purchaser (GSTT) are considered at both local and national levels and inform Department of Health (DH) and Commercial Medicines unit (CMU) of any local shortages. 4. Monitor and review Trust usage 4.1 The HASAP is responsible for overseeing the overall use of HAS by the Trust and for periodically reviewing data. 4.2 This data shall be reported to the Drug and Therapeutics Committee and users of HAS. 5. Clinical Trials 5.1 Review and approve research proposals for studies involving HAS 22