Patient Blood Management Guidelines: Module 1

Critical Bleeding Massive Transfusion

| Clinical practice guidance based on evidence or consensus |

4.1 Effect of physiological parameters on outcomes

Question 1 (prognostic)

In patients with critical bleeding requiring massive transfusion, what is the effect of variation of physiologic, biochemical and metabolic (including temperature) parameters on morbidity, mortality and transfusion rate?

The evidence was obtained from 10 studies, comprising 8 retrospective^15,^61-67 and 2 prospective^68,69 analyses of registry data, medical records or charts.

Most of the studies of critically bleeding and transfused patients found that reduced core body temperature,^14,^60-62 lower pH or higher base deficit,^14,^61,^62,^65-68 coagulopathy^14,^62,⁶⁸ and thrombocytopenia^14,⁶⁸ were associated with increased mortality. However, two studies did not find an association with reduced body temperature^63,⁶⁷ and one study found no association with higher base deficit.⁶³

Five studies calculated the odds of predicting mortality (or survival) among patients with critical bleeding requiring massive transfusion.^15,^61,^64,^65,⁶⁸ Although not strictly a study of massive transfusion (because patients included received ≥ 5 units RBCs within 24 hours of admission), Mitra found that a number of factors were independent predictors of mortality:¹⁵

hypothermia (odds ratio [OR] = 0.72; 95%CI: 0.56, 0.92; p = 0.01)
thrombocytopenia (OR = 0.99; 95%CI: 0.98, 1; p< 0.01)
increased international normalised ratio (INR) (OR = 1.62; 95%CI: 1.18, 2.24; p< 0.01)
prolonged partial thromboplastin time (OR = 1.01; 95%CI: 1.01, 1.02; p< 0.01)
low fibrinogen level (OR = 0.52; 95%CI: 0.28, 0.99; p = 0.05)
low pH (OR = 0.01; 95%CI: 0, 0.29; p = 0.01)
low bicarbonate levels (OR = 0.86; 95%CI: 0.77, 0.96; p = 0.01).

Insufficient studies were found to provide an evidence statement on the effects of hypothermia, metabolic acidosis, thrombocytopenia and coagulopathy on morbidity or transfusion rate.

Mortality was found to be highest where acidosis and hypothermia occurred with coagulopathy.¹⁵ This combination has become known as the ‘lethal triad’ or ‘bloody vicious cycle’. To improve patient survival and outcomes, management strategies should be directed to avoiding or reducing the extent of these complications.

Evidence statement

Hypothermia, metabolic acidosis,thrombocytopenia and coagulopathy may be independently associated with increased mortality.^15,^61,^63-68 (See evidence matrix 1 in Appendix E.)
= A = B = C = D (See table 2.2)

Practice points

PP1	In patients with critical bleeding requiring massive transfusion, the following parameters should be measured early and frequently: temperature acid–base status ionised calcium haemoglobin platelet count PT/INR APTT fibrinogen level. With successful treatment, values should trend towards normal.

PP2	Values indicative of critical physiologic derangement include: temperature < 35°C pH < 7.2, base excess > –6, lactate > 4 mmol/L ionised calcium < 1.1 mmol/L platelet count < 50 × 10⁹/L PT > 1.5 × normal INR > 1.5 APTT > 1.5 × normal fibrinogen level < 1.0 g/L

APTT, activated partial thromboplastin time; INR, international normalised ratio; PP, practice point; PT, prothrombin time