An Audit of Poor Response To Erythropoeitin Therapy. September 1998

Transcription

1 1 An Audit of Poor Response To Erythropoeitin Therapy September 1998 Prepared By: Nicola Austerberry Renal Audit Facilitator Phil Kalra Consultant Nephrologist

2 2 1 Introduction The topic for this audit is of national and regional priority. This audit could not have progressed without the input of the anaemia co-ordinators in post at each of the five main renal units in the North West Region. Many patients are now treated with Erythropoietin (EPO) but many patients are still not reaching the target of 10g/dl as recommended by the Renal Association. The working group for this audit recognised that with a target Hb of 10-12g/dl, many patients would fall just below the lower limit, without necessarily being a non-responder. Therefore, a decision was made to use 9g/dl as a target for this audit. 2 Aims of the Audit 1. To establish the proportion of patients who respond poorly to Erythropoeitin therapy. 2. To ascertain the proportion of patients for whom the poor response to EPO has an established cause. 3. To determine the proportion of patients whose poor response has been adequately investigated. 4. To determine the proportion of patients for whom action has been taken to remedy the poor response. 3 Methods Data was collected by the anaemia co-ordinator for all patients fitting the criteria for poor response as set out below. Data consisted of EPO therapy received, iron status, investigations performed ( as listed below) and any action taken. The data has then been analysed by the audit staff. Investigations: Contributory Factors Vitamin B12 and Folate Missed EPO Dose PTH CRP Chronic Infection/Inflammation Ferritin Albumin Hypertension Aluminium Bleeding FOB Recognised Bone Disease Dialysis Adequacy 4 Population All patients, including pre-dialysis patients, who commenced EPO treatment prior to 1 st January The following were recruitment criteria: 1 st Hb result, on or after 1 st April, below 9g/dl. Patients with an Hb >9g/dl but who, prior to the audit period, had consistently lower readings. This particularly captured patients who had been transfusion dependent.

3 3 5 Results The audit produced a population of 123 patients reported as poor responders to Erythropoietin therapy. This was 12% of the total population (n1001) receiving EPO therapy. The division of these patients is shown in the following table: Unit Audit Population Male Female EPO Population Hope 25 (14%) MRI 19 (10%) RPH 20 (7%) Withington 13 (10%) RLUH 46 (21%) Region 123 (12%) Of the poor responders, 76% were on haemodialysis and 22% CAPD. Only 2 pre dialysis patients were reported as responding poorly to therapy. The split between the different modes of dialysis can be seen below: Unit Population Haemo CAPD Pre-Dialysis Hope (60%) 9 (36%) 1 (4%) MRI (74%) 5 (26%) 0 RPH (85%) 3 (15%) 0 Withington (77%) 2 (15%) 1 (8%) RLUH (83%) 8 (17%) 0 Region (76%) 27 (22%) 2 (2%) 6 Haemoglobin Levels Each patient was recruited to the audit after presenting with an Hb result <9g/dl. The lowest and mean results are tabled below: Hope MRI RPH Withington RLUH lowest mean St Dev Some of these patients were reliant on blood transfusion to maintain their haemoglobin. The mean Hb is therefore falsely high because the time period between blood transfusion and blood sampling has not been taken into account.

4 4 34% of the poor responders were reported to have achieved a target of 9g/dl or above in the previous 6 months without blood transfusion. It is therefore likely that these patients present with a short term or reversible problem. The patients who have only achieved the target following transfusion or who have never achieved target are the ones who need monitoring most closely. The table below illustrates the percentage of the poor responder patients having achieved 9g/dl without transfusion at the individual units: Unit (n) % achieving target Hope (25) 46% MRI (19) 42% RPH (20) 50% Withington (13) 46% RLUH (46) 17% Region (123) 34% The patients in the above grouping can therefore be considered to be temporary poor responders to EPO therapy. 7 Erythropoietin Dose The dose of EPO given to patients with a poor response was recorded for each patient and the mean dose per kg per week was calculated for each unit and for the region as a whole: Unit (n) Mean dose/kg/wk Hope (25) 119 MRI (19) 127 RPH (20) 110 Withington (13) 96 RLUH (46) 86 Region (123) 103 The mean EPO dose is approximately twice as great in poor responders than responders to EPO.

5 5 8 Contributory Factors to Poor Response The following factors were considered as contributors to poor response to EPO therapy: Infection and inflammation Overt bleeding Iron deficiency - defined as ferritin <100units Missed dosage of EPO Hypertension - defined as > 160/90 (regularly) causing EPO dose to be withheld Severe bone disease - defined as PTH >400pg/ml Poor dialysis adequacy: in haemodialysis patients Kt/V <1.2 or URR <65% in CAPD patients Kt/V <1.7 7% of the audit population were reported not to have any of these factors and were therefore classed as having an unknown cause for poor response to EPO therapy. The percentage of patients reported as having each factor, for each unit and the region as a whole, is detailed in the table below: Contributory Factor Hope (n25) MRI (n19) RPH (n20) SMUH (n13) RLUH (n46) Total (n123) Infection 40% 58% 40% 23% 26% 36% Inflammation 40% 21% 45% 8% 19% 27% Bleeding 12% 31% 25% 15% 4% 15% Iron Deficiency 12% 31% 30% 8% 15% 19% Missed EPO 24% 47% 45% 46% 17% 31% Hypertension 32% 10% 35% 8% 17% 21% Bone Disease 24% 26% 25% 38% 22% 25% Adequacy 20% 21% 20% 8% 46% 28% Multiple causative factors were reported in many of the patients.

6 6 9 Investigations into Poor Response The percentage of patients reported to have a result for the following investigations was documented. A result from the previous twelve months was requested except for ferritin and albumin which was requested as a monthly result: Investigation Hope (n25) MRI (n19) RPH (n20) SMUH (n13) RLUH (n46) Total (n123) Ferritin 96% 100% 100% 100% 100% 99% CRP 60% 16% 20% 54% 91% 58% B12 76% 100% 70% 69% 33% 62% Folate 72% 100% 70% 69% 33% 62% PTH 92% 100% 100% 100% 89% 94% Aluminium 76% 26% 95% 77% 67% 68% Albumin 76% 100% 90% 100% 100% 93% Adequacy 60% 84% 75% 46% 83% 73% 10 Iron Therapy and Iron Deficiency The number of patients receiving iron therapy and the route of treatment was recorded. 56% of the patients were receiving oral therapy and 25% IV. 9% were reported to be receiving both oral and IV. No data was received for 10% of patients but it was not clear whether these patients were not receiving treatment or the data was missing. Using the definition of ferritin <100µ/l for iron deficiency, 24 (19%) patients fitted this criteria. Of these, 12 were already receiving iv iron therapy and the other 12 were reported as waiting to commence which therefore implies the problem was being addressed.. An additional 7 patients not necessarily fulfilling the criteria for iron deficiency were reported as being given IV iron as management for poor response to EPO. Only 2% of the patients were reported to have no action taken to remedy poor response.

7 7 Summary 12% of patients receiving EPO are not achieving an Hb >9g/dl 76% of the poor responders to EPO are haemodialysis patients. 34% of patients may have an intercurrent illness which makes them temporarily non-responders. Mean EPO dose is approximately 2 times greater in poor responders than responders to EPO therapy. As this is only 103 units/kg/wk, there may be scope for improved response, in some patients, with an increase in EPO dose. There are often several contributory factors for poor response. The following are potentially reversible factors: Bone Disease (25%) Poor Adequacy (28%) Bleeding (15%) Iron Deficiency (19%) Most units check PTH and Ferritin regularly There appears to be poor monitoring of CRP, B12, Folate and Dialysis adequacy in some units.

8 8 Guidelines for the Treatment of Poor Response to EPO Therapy. Identification Early identification of poor response to therapy i.e. by three months after completion of the initiation period. Definition of poor response: Hb is persistently < 10g/dl, or the patient is transfusion dependent, despite adequate doses of EPO. Assessment All possible factors contributing to non response should be assessed at time of identification: Ferritin/iron deficiency PTH Occult Bleeding - GI or PV Intercurrent infection or inflammation Inadequacy of dialysis Aluminium - (important to rule out but rarely a factor.) Non-compliance with treatment Treatment Early treatment of contributory factors, in particular: Iron deficiency Severe hyperparathyroidism Occult Bleeding Intercurrent Infection/inflammation In the event that the patient is iron replete (ferritin>100µ/l ), then increase EPO dose in sequential steps to the maximum dose appropriate. (usually up to 200 units/kg/wk. ) Consider improving dialysis adequacy where this is a possible contributory factor. Maintain patients under regular review. We plan to re-audit after a twelve month period..