Effect of a blood conservation device in patients with preserved admission haemoglobin in the intensive care unit.
Abstract: An important iatrogenic cause of anaemia in the intensive care unit is loss of the discarded blood during phlebotomy via indwelling vascular catheters. A closed system blood conservation device has previously been shown to reduce the need for blood transfusion and to blunt the decrease of haemoglobin in intensive care unit patients. However, such a device may not benefit patients who are admitted with a relatively preserved haemoglobin.

In this sub-group analysis of a before-and-after study, 128 patients had admission haemoglobin [greater than or equal to] 115 g/l and did not receive any blood transfusions while in the intensive care unit. In the control group of 50 patients a blood conservation device was not used, while in the active group of 78 patients the device was used. Use of the blood conservation device did not affect the haemoglobin trends when both groups were compared using the general linear model.

For patients with admission haemoglobin [greater than or equal to] 115 g/l, use of a blood conservation device does not affect the subsequent rate of haemoglobin decline in the intensive care unit. These patients are unlikely to benefit from the use of such devices.

Key Words: blood conservation, anaemia, intensive care unit, packed red blood cell transfusion
Article Type: Report
Subject: Blood transfusion (Research)
Critical care medicine (Research)
Anemia (Causes of)
Phlebotomy (Research)
Veins (Puncture)
Veins (Research)
Authors: Mukhopadhyay, A.
See, K.C.
Chan, Y.H.
Yip, H.S.
Phua, J.
Pub Date: 05/01/2011
Publication: Name: Anaesthesia and Intensive Care Publisher: Australian Society of Anaesthetists Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2011 Australian Society of Anaesthetists ISSN: 0310-057X
Issue: Date: May, 2011 Source Volume: 39 Source Issue: 3
Topic: Event Code: 310 Science & research
Geographic: Geographic Scope: Singapore Geographic Code: 9SING Singapore
Accession Number: 260691515
Full Text: Anaemia can affect up to 90% of patients by day three in the intensive care unit (ICU) (1). The cause of anaemia in ICU is multifactorial, including iatrogenic blood loss from repeated blood-taking for diagnostic tests (2). Therefore packed red blood cell (PRBC) transfusions are also common, occurring in up to 44% of critically ill patients (1). However, blood transfusions are not innocuous: apart from the usual risk of transfusion-associated infections, fluid overload and acute lung injury, they are associated with increase in mortality, ventilator-associated pneumonia (3), hospital length of stay and economic costs (4,5).

The use of blood conservation devices has proven promising in reducing iatrogenic blood loss from diagnostic testing (6-8). These devices work by conserving and returning blood drawn out just prior to the blood sampling. We have previously shown that with a restrictive transfusion strategy (9), saving

repeated small volumes of blood can translate to an overall reduction in PRBC transfusion requirements and preservation of haemoglobin (Hb) (10,11).

Nonetheless, the use of such devices leads to additional cost and it is likely that not every patient will benefit. Using data from our previously reported before-and-after study conducted from 2008 to 2009 (11), we aimed to test our hypothesis that these devices will not significantly alter the Hb trend for patients with relatively normal levels of Hb on admission.

METHODS

Study design

This is a sub-group analysis of a previously reported before-and-after study conducted in the 12-bed medical ICU of our university hospital (11). The 'before' period included patients from January to June 2008 (control group). In the active group a blood conservation device was used from the start of the 'after' period, from July 2008 to March 2009 (active group). The study was approved by our institutional review board and ethics committee. Informed consent was obtained in the active group. Requirement of consent was waived for the control group.

Patients

We included all patients admitted to the medical ICU who 1) were aged 18 years and above; 2) were expected to stay more than 24 hours; 3) had an indwelling intra-arterial catheter inserted and 4) had Hb levels of 115 g/l or more on admission to the ICU. We excluded patients who 1) were expected to stay less than 24 hours, 2) had active gastrointestinal or other bleeding as the primary cause of ICU admission, or 3) had any blood transfusion. We had intentionally excluded patients with any blood transfusion during their ICU stay, as blood transfusion would buffer any drop in Hb. The following data were collected prospectively: patient demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, daily Hb levels from ICU admission until day 10 and just before any PRBC transfusion, details of PRBC transfused, need for any renal replacement therapy (RRT), ICU length of stay and mortality. For the patients who died in ICU, the last Hb before death was recorded. Patients were followed up until hospital discharge, death or up to 28 days of ICU stay, whichever was later.

Interventions

We used the venous arterial blood management protection system (Edwards Lifesciences, Irvine, USA) for the active group, as described in our previous study (11).

Statistical analysis

Continuous variables were expressed as mean [+ or -] standard deviation and compared using Student's t-test. Categorical variables were expressed as proportions and compared with the Fisher's exact test. All statistical tests were two-sided and P <0.05 was considered significant. Multivariate analysis of Hb trend was done using the general linear model controlling for gender, age, duration of ICU stay, RRT duration (hours) and APACHE II score. Statistical analyses were conducted using SPSS 17.0 (Chicago, Illinois, USA).

RESULTS

Patient enrolment is shown in Figure 1. Out of a total of 250 patients (80 patients in the control group, 170 patients in the active group) in the original study, a total of 128 patients were available for this sub-group analysis. Fifty patients did not receive the blood conservation device (control group), while 78 patients used the device (active group). For the whole cohort, mean age was 60.6 [+ or -] 18 years, 66% were men, mean APACHE II score on day one of ICU admission was 18.4 [+ or -] 7.9, ICU and hospital mortality were 18% and 28.9% respectively, and the patients stayed 6.4 [+ or -] 4.7 days in the ICU. The two groups did not differ significantly in their baseline characteristics or clinical outcomes (Table 1).

Univariate comparisons of Hb across time showed no statistically significant differences (Figure 2).

Multivariate analysis using the general linear model controlling for gender, age, duration of ICU stay, RRT duration (hours) and APACHE score did not reveal any significant interaction between the use of the blood conservation device and the Hb decline while in the ICU (P=0.660). The rate of Hb decline was 4.86 g/l/day (rate of decrease 3.4% per day, 95% confidence interval 5.91 to 3.8) in the control group and 4.58 g/l/day (rate of decrease 3.1% per day, 95% confidence interval 5.38 to 3.77) in the active group (P=NS).

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

DISCUSSION

Our results show that for patients with preserved Hb (as defined by Hb [greater than or equal to] 115 g/l) on admission to ICU, the use of a blood conservation device does not alter the subsequent rate of Hb decline. We defined 'preserved' Hb ([greater than or equal to] 115 g/l) based on previous studies where mean admission Hb levels were 110 to 113 g/l (1,2). Previous studies, have shown that use of a blood conservation device led to better preservation of Hb in ICU (8,11). However, no such difference was found in this sub-group analysis with higher Hb on admission.

Patients in ICU require multiple phlebotomies for various laboratory tests, more than patients in the general ward (12), especially in the first 24 hours of admission when approximately 41 ml of blood is lost (13). The presence of an indwelling central venous or arterial catheter makes blood sampling easier (2) and therefore contributes to the iatrogenic anaemia as the first few millilitres of infusate-blood mixture obtained when collecting blood from a fluid-infusing catheter is discarded. Use of a blood conservation device leads to the preservation of such discarded volumes (6), thus maintaining the Hb. In our previous study we have shown that use of a blood conservation device leads to less PRBC transfusion (11) in the setting of an evidence-based restrictive transfusion practice (9). However lowering Hb to the transfusion threshold is dependent on many factors, including admission Hb, severity of illness (13,14) and frequency of phlebotomy. The present study shows that a blood conservation device is not useful in preventing anaemia in patients with relatively preserved Hb at admission.

Anaemia remains the main reason for blood transfusions in ICU (1) and measures to prevent anaemia should logically lead to decreased PRBC transfusion. Apart from direct cost, PRBC transfusion is associated with other known risks. Blood-borne infections, non-infectious complications including allergic, anaphylactic and haemolytic transfusion reactions, transfusion-related acute lung injury and transfusion-associated circulatory overload are common and lead to significant morbidity and mortality (15). Recently published studies also show that blood transfusion in ICU is associated with increased risk of infection (16), ventilator-associated pneumonia and acute respiratory distress syndrome (3,17). Unfortunately, the use of erythropoietin does not avoid blood transfusion in critically ill patients (18). One way to reduce blood transfusion is to adopt a restrictive rather than a liberal transfusion strategy. Hebert et al demonstrated that maintaining Hb in the range of 70 to 90 g/l is at least equivalent to maintaining Hb levels greater than 100 g/l with blood transfusion (9). A second way to reduce blood loss through phlebotomy is to use paediatric-sized instead of larger adult-sized tubes for blood sampling (19,20). Another way to reduce the need for blood transfusion is to mitigate blood loss during phlebotomy using blood conservation devices (11). However, we recognise that not every patient in the ICU would need specialised blood conservation devices. Our results give guidance to the group which is more likely to benefit from blood conservation.

In our study, the Hb levels declined throughout the first 10 days of ICU stay, with the greatest drop occurring between days one and two. This is consistent with the CRIT study (1), which also showed that when the baseline Hb is above 120 g/l the chance of PRBC transfusion is low and if transfused, time to first transfusion is longer. Our study adds to this knowledge: the additional use of a blood conservation device is unlikely to change the above course.

It is well-known that frequent phlebotomies in ICU lead to increased blood loss during the admission. Venesection alone accounted for blood loss of averaging 85 ml on the first day and 66 ml thereafter in a survey of ICUs in Britain (21). Von Ahsen and colleagues have shown that the total amount of diagnostic blood loss remains the most significant factor for subsequent transfusion (22) and arterial blood gas analysis remains the most frequent source of diagnostic blood loss (23). If diagnostic blood loss contributes to anaemia and use of a blood conservation device leads to preservation of the discarded blood volume, why does this sub-group analysis fail to show any beneficial effect of such a device on the Hb trend? Our data suggest that patients with higher admission Hb were less sick (as compared by APACHE II score) and received less RRT (data not shown). Most patients on RRT received citrate anticoagulation, which again required frequent arterial blood gas sampling. This is in accordance with previous studies which showed that sicker patients require more diagnostic blood tests (13,14) and hence are at greater risk of anaemia. These patients would therefore benefit more from a blood conservation device. It is likely that the less sick patients in this sub-group analysis received fewer phlebotomies and RRT and therefore a blood conservation device was less effective in this group of patients.

There are several important limitations to our study. The original study was a before-and-after study and given the limitations of a historical control study, the results need to be confirmed with a prospective randomised controlled tiral. This subgroup analysis of data was planned, but due to the design of the original before-and-after study, a sample size calculation of the sub-group analysis was not possible. We have chosen 'preserved' Hb ([greater than or equal to] 115 g/l) based on previous studies and it is unlikely that a higher Hb on admission will alter the results. Phlebotomy data were not collected in either the control or active group. We studied patients in our medical ICU only and our results need to be confirmed in a wider patient population including other ICUs. We collected Hb data up to a maximum of 10 days in the ICU, and it is unknown if blood conservation devices will benefit long-stayers beyond that time. However, this is unlikely as the rate of phlebotomy declines with length of stay (1,13). Lastly, we used the venous arterial blood management protection device and it remains to be seen if our findings are applicable to other blood conservation devices.

In conclusion, for patients with preserved admission Hb to the ICU ([greater than or equal to] 115 g/l), use of a blood conservation device does not affect the subsequent rate of Hb decline. It is therefore unlikely that these patients will benefit from the use of such devices.

DECLARATION OF INTEREST

This study was done with the Health Quality Improvement Fund from Ministry of Health, Singapore.

REFERENCES

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(18.) Corwin HL, Gettinger A, Fabian TC, May A, Pearl RG, Heard S et al. Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med 2007; 357:965-976.

(19.) Mahdy S, Khan EI, Attia M, O'Brien BP, Seigne P. Evaluation of a blood conservation strategy in the intensive care unit: a prospective, randomised study. Middle East J Anesthesiol 2009; 20:219-223.

(20.) Smoller BR, Kruskall MS, Horowitz GL. Reducing adult phlebotomy blood loss with the use of pediatric-sized blood collection tubes. Am J Clin Pathol 1989; 91:701-703.

(21.) Tarpey J, Lawler PG. Iatrogenic anaemia? A survey of venesection in patients in the intensive therapy unit. Anaesthesia 1990; 45:396-398.

(22.) von Ahsen N, Muller C, Serke S, Frei U, Eckardt KU. Important role of nondiagnostic blood loss and blunted erythropoietic response in the anemia of medical intensive care patients. Crit Care Med 1999; 27:2630-2639.

(23.) Andrews T, Waterman H, Hillier V. Blood gas analysis: a study of blood loss in intensive care. J Adv Nurs 1999; 30:851-857.

A. MUKHOPADHYAY *, K. C. SEE ([dagger]), Y. H. CHAN ([double dagger]), H. S. YIP ([section]), J. PHUA **

Department of Medicine, National University Hospital, Singapore

* M.B., B.S., M.D., M.R.C.P., F.R.C.P., E.D.I.C., Senior Consultant.

([dagger]) M.B., B.S., M.R.C.P., E.D.I.C., Associate Consultant.

([double dagger]) Ph.D., Head, Biostatistics Unit, Yong Loo Lin School of Medicine.

([section]) M.B., B.S., M.R.C.P., Associate Consultant.

** M.B., B.S., M.R.C.P., E.D.I.C., Consultant.

Address for correspondence: Dr A. Mukhopadhyay, Division of Respiratory & Critical Care Medicine Department of Medicine, National University Hospital, 1E Lower Kent Ridge Road, NUHS Tower Block Level 10, Singapore 119228. Email: amartya.mukherjee@gmail.com

Accepted for publication on December 13, 2010.
TABLE 1

Baseline clinical characteristics of the control and active groups

                            Control group        Active group
                            without blood        with blood
                            conservation         conservation
                            device (n=50)        device (n=78)

Underlying pathology
  Sepsis--pulmonary         14 (28.0%)           30 (38.5%)
  Sepsis--extrapulmonary    9 (18.0%)            13 (23.1%)
  Airway disease            6 (12.0%)            13 (23.1%)
  Neurological              2 (4.0%)             7 (9.0%)
  Renal failure,            3 (6.0%)             3 (3.8%)
    metabolic acidosis
  Acute pulmonary oedema    3 (6.0%)             3 (3.8%)
  Others                    13 (26.0%)           9 (11.5%)
Age, y                      61.7 [+ or -] 19.3   60.0 [+ or -] 17.3
Male/female                 33/17                51/27
ICU LOS                     6.0 [+ or -] 3.4     6.6 [+ or -] 5.4
APACHE II score             18.0 [+ or -] 7.6    18.7 [+ or -] 8.2
RRT, %                      9                    10
Hb on admission, g/l        132                  138

                            P value

Underlying pathology
  Sepsis--pulmonary         0.306
  Sepsis--extrapulmonary    0.513
  Airway disease            0.324
  Neurological              0.482
  Renal failure,            0.872
    metabolic acidosis
  Acute pulmonary oedema    0.872
  Others                    0.063
Age, y                      0.608
Male/female                 1.000
ICU LOS                     0.494
APACHE II score             0.616
RRT, %                      1.000
Hb on admission, g/l        0.130

ICU=intensive care unit, LOS=length of stay, APACHE=Acute Physiology
and Chronic Health Evaluation, RRT=renal replacement therapy,
Hb=haemoglobin.
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