Use of intravenous immune globulin in the ICU: a retrospective review of prescribing practices and patient outcomes.

RATIONALE: Intravenous immune globulin (IVIG) is a pooled human blood product. Much of IVIG use in Canada is prescribed for 'unlabelled' or 'off-label' indications. Due to costs, risk of use and limited supply, knowledge about the use of IVIG is important. We collected data regarding the usage of IVIG and outcomes of patients receiving IVIG in the intensive care units (ICUs) of two community and three academic hospitals. METHODS: We reviewed the charts of adult patients who received IVIG in the five ICUs over a 5-year period. Data collection included demographics, severity of illness, indication for and dose of IVIG, mortality and adverse effects. On the basis of a classification developed by Canadian Blood Services, the indications for IVIG were then classified as 'appropriate' or 'inappropriate'. RESULTS: One hundred and forty-five patients received IVIG in the ICU. In all, 19% of IVIG prescriptions were for 'appropriate' indications and 7% were 'inappropriate'. The remaining 74% were prescribed for indications with some evidence to support their use. Three indications accounted for 50% of all IVIG prescribed: Guillain-Barre syndrome (GBS), necrotising fasciitis (NF) and toxic epidermal necrolysis (TEN). Both the community and academic centres prescribed IVIG for similar indications. Adverse effects associated with IVIG administration included deep vein thrombosis/pulmonary embolism, fever and renal failure, although direct causation related to IVIG could not be established. The overall mortality rate was 55%. CONCLUSIONS: IVIG is used relatively infrequently in the critical care setting. The most common indications were GBS, TEN and NF. Mortality was high. There was no difference between community and academic ICUs.

Changes in intravenous immunoglobulin prescribing patterns during a period of severe product shortages, 1995-2000.

BACKGROUND AND OBJECTIVES: Canadian consumption of intravenous immunoglobulin (IVIG) has increased dramatically since it was first marketed in the early 1980s, and Canada is now the world's largest per capita consumer. During the late 1990s, worldwide product shortages of IVIG occurred. This study was designed to identify the disease conditions for which IVIG was being prescribed in academic hospitals during this period, and to explore the effects that IVIG shortages had on prescribing patterns. MATERIALS AND METHODS: Blood bank and pharmacy records of IVIG distribution were collected retrospectively from four Toronto teaching hospitals for the period 1995-2000. These records were then cross-referenced with patient medical records to determine the indication for IVIG administration. RESULTS: A total of 100,208 g of IVIG was prescribed to 429 patients over a 6-year period. Most of the IVIG consumption was in patients with haematological (22%) or neurological (20%) conditions, in recipients of bone marrow transplants (19%) and in patients with infectious disease-related conditions (including congenital and acquired hypogammoglobulinaemia, 18%). Dermatological conditions (7%) were the most rapidly growing indication for IVIG usage during the 6-year period of review, increasing from 0% of annual IVIG usage in 1995 to 16% in 2000. Over 80% of the diseases treated were supported by published recommendations. After 1997 there was an abrupt decline in the annual number of patients treated, primarily owing to a decline in single-use recipients. Annual consumption of IVIG, however, remained stable. CONCLUSIONS: IVIG shortages were followed by a decrease in the number of single-use recipients, who probably represented empirical use of IVIG; this had little effect on the total amount of IVIG distributed annually. Stricter adherence to currently available published recommendations may not be the optimal means of controlling IVIG use within an academic hospital setting. Rather, emphasis may be better placed on improving the evidence base upon which these recommendations are made, for example by conducting controlled prospective clinical trials.

Prolonged in vitro hemolysis of EDTA-anticoagulated blood after a delayed hemolytic transfusion reaction.

BACKGROUND: A novel case where in vitro hemolysis was observed in plasma, but not in serum samples, obtained after the onset of a severe delayed hemolytic transfusion reaction is presented. CASE REPORT: A 54-year-old woman received 2 units of blood during an orthopedic procedure. She had received transfusion 30 years earlier, and testing before transfusion revealed no alloantibodies. The patient returned 12 days after the transfusion with a Hb level of 54 g per L due to a severe delayed hemolytic reaction caused by anti-K. The plasma and serum samples were grossly hemolysed on Day 12. On Day 14, the serum samples showed no evidence of hemolysis; however, the EDTA sample remained grossly hemolysed. This discrepancy was not identified until Day 19. Due to concerns of ongoing apparent severe hemolysis, the patient was unnecessarily treated with IVIG and corticosteroids. The in vitro hemolysis was still present at 75 days, despite complete normalization of her Hb, bilirubin, and LDH levels. The phenomenon had resolved by 125 days. CONCLUSION: This in vitro artifact has not been previously reported and the mechanism remains unclear. Both plasma and serum samples should be observed for hemolysis when evaluating a patient with a severe delayed hemolytic transfusion reaction.

Reporting of near-miss events for transfusion medicine: improving transfusion safety.

BACKGROUND: Half of the reported serious adverse events from transfusion are a consequence of medical error. A no-fault medical-event reporting system for transfusion medicine (MERS-TM) was developed to capture and analyze both near-miss and actual transfusion-related errors. STUDY DESIGN AND METHODS: A prospective audit of transfusion-related errors was performed to determine the ability of MERS-TM to identify the frequency and patterns of errors. RESULTS: Events and near-miss events (total, 819) were recorded for a period of 19 months (median, 51/month). No serious adverse patient outcome occurred, despite these events, with the transfusion of 17,465 units of RBCs. Sixty-one events (7.4%) were potentially life-threatening or could have led to permanent injury (severity Level 1). Of most concern were 3 samples collected from the wrong patient, 13 mislabeled samples, and 22 requests for blood for the wrong patient. Near-miss events were five times more frequent than actual transfusion errors, and 68 percent of errors were detected before blood was issued. Sixty-one percent of events originated from patient areas, 35 percent from the blood bank, and 4 percent from the blood supplier or other hospitals. Repeat collection was required for 1 of every 94 samples, and 1 in 346 requests for blood components was incorrect. Education of nurses and alterations to blood bank forms were not by themselves effective in reducing severe errors. An artifactual 50-percent reduction in the number of errors reported was noted during a 6-month period when two chief members of the event-reporting team were on temporary leave. CONCLUSION: The MERS-TM allowed the recognition and analysis of errors, determination of patterns of errors, and monitoring for changes in frequency after corrective action was implemented. Although no permanent injury resulted from the 819 events, innovative mechanisms must be designed to prevent these errors, instead of relying on faulty informal checks to capture errors after they occur.

An evaluation of the process and costs associated with targeted lookbacks for HCV and general notification of transfusion recipients.

BACKGROUND: The Commission of Inquiry on the Blood System in Canada recommended that hospitals notify patients who received blood between 1978 and May 1990 of the risks of contracting HIV (up to the end of 1985 only) and HCV infection. The commission also recommended that patients should be informed of any transfusion received. STUDY DESIGN AND METHOD: General notifications for HIV and HCV for this period were begun in mid-1994. Notification after discharge of transfusions received after May 1990 was begun in 1997. Targeted HCV lookback was performed from 1995 to 1999. RESULTS: Of 21,016 transfusion recipients from January 1978 to May 1990 identified in the general look-back process and believed still alive, 13,549 (64%) were presumed contacted, by registered mail. The overall contact rate for the ongoing notifications (transfusions after May 1990) cannot be accurately determined, as registered mail was not used and a reply not requested. The total cost for these two processes was CAN$373,481, or $13 per patient believed contacted. Most (56%) of this cost was for the conversion to electronic form of paper transfusion records for the period 1978 through early 1984. In the targeted HCV lookback program 1995 through 1999, 94 percent of 256 recipients of specific components identified as likely to have transmitted HCV either were contacted or had died. Of 84 living recipients, 47 (56%) are HCV positive. The last documented potential seroconversion occurred after a transfusion in November 1991, during the period of first-generation EIA testing. If the targeted HCV lookback had been restricted to transfusions after 1987, as the FDA recommended, we would have failed to identify 39 living patients, of whom 21 are HCV positive. The cost per HCV-positive patient notified in the targeted HCV lookback was CAN $4,174. CONCLUSION: The cost of compliance with the com-mission's recommendations was CAN$569,636. Over 28,000 of 36,773 transfusion recipients were notified or presumed notified, and 272 targeted HCV lookbacks to 256 recipients were performed. Performance of this task required the existence of transfusion records back to 1978, conversion of paper records to electronic form, and adequate secretarial and financial support.

Influence of total body irradiation on infections after autologous bone marrow transplantation.

Infectious complications were analysed in 50 consecutive autologous bone marrow transplant (ABMT) patients treated with high dose etoposide and melphalan, 30 of whom also received total body irradiation (TBI). Fever developed in 44 patients and bacteremia was documented in 13 (26%). Patients given TBI had increased susceptibility to bacteremia; 11 of 30 patients who received TBI had positive blood cultures, in contrast to two of the 20 who did not (p = 0.035). In addition, patients who received TBI had significantly more severe diarrhea (p = 0.037) when compared with those who received chemotherapy alone. Thirty-five patients treated with trimethoprim-sulfamethoxazole prophylaxis had a signficantly lower incidence of gram-negative bacteremia (p = 0.024). However, when those patients who received trimethoprim-sulfamethoxazole until neutrophil recovery were analysed alone, those who were also given TBI still had significantly more bacteremia (p = 0.047). Forty-seven patients with follow-up of more than 12 months are available for analysis of varicella zoster (VZV) infections. Of the 29 patients who received TBI, 11 (38%) developed VZV infections, in contrast to one of 18 patients (6%) treated with chemotherapy alone (p = 0.013). These results suggest that addition of TBI to the intensive therapy regimen for ABMT is associated with significantly more bacteremia and late VZV infections.