Blood transfusions in sepsis, the elderly and patients with TBI

Transcription

1 Blood transfusions in sepsis, the elderly and patients with TBI Shabbir Alekar MICU, CH Baragwanath Academic Hospital & The University of the Witwatersrand CCSSA Congress 11 June 2015

2 Packed RBC - complications Early Haemolytic reactions Non haemolytic febrile reactions Allergic reactions to proteins TRALI Bacterial contamination TACO Hypothermia Hyperkalaemia Coagulopathy Late Infection transmission Viral Bacterial Parasites GVHD Iron overload Immune sensitisation

3 Talk outline The aetiology of anaemia in ICU Physiological adaptation to anaemia The physiological rationale for PRBCT The (un)physiological effect of PRBCT The evidence Sepsis The elderly TBI Conclusion

4 Delivery of oxygen Delivery of O₂ = Cardiac output x oxygen content of arterial blood DO₂ = CO X CaO₂

5 Delivery of oxygen Delivery of O₂ = Cardiac output x oxygen content of arterial blood DO₂ = CO X CaO₂ CaO₂ = (1.34 x Hb x %saturation) + (PaO₂ x 0.003)

6 Delivery of oxygen Delivery of O₂ = Cardiac output x oxygen content of arterial blood DO₂ = CO X CaO₂ CaO₂ = (1.34 x Hb x %saturation) + (PaO₂ x 0.003)

7 Delivery of oxygen Delivery of O₂ = Cardiac output x oxygen content of arterial blood DO₂ = CO X CaO₂ CaO₂ = (1.34 x Hb x %saturation) + (PaO₂ x 0.003)

8 Aetiology of anaemia in critical illness Shortened RBC life span Haemolysis Phlebotomy losses Oozing from injury sites Invasive procedures GIT losses

9 Aetiology of anaemia in critical illness Shortened RBC life span Haemolysis Phlebotomy losses Oozing from injury sites Invasive procedures GIT losses Diminished RBC production Nutritional deficiencies Anaemia of inflammation

10 Anaemia of inflammation Inflammation increased IL-1, IL-6 and TNF-α Impaired RBC production Altered iron metabolism Altered erythropoetin production and signalling

11 Many studies have shown a worse outcome in patients with anaemia Carson et al. Lancet 1996; 348: Khamies et al. Chest 2001; 120: Chambellan et al. Chest 2005; 128: Ezekowitz et al. Circulation 2003; 107:

12 Many studies have shown a worse outcome in patients with anaemia Carson et al. Lancet 1996; 348: Khamies et al. Chest 2001; 120: Chambellan et al. Chest 2005; 128: Ezekowitz et al. Circulation 2003; 107: But anaemia may be a marker of disease severity rather than a cause of the poor outcome

13 Physiological adaptation to anaemia

14 Respiratory adaptation Increased minute ventilation Improved V/Q matching leads to improvement in oxygenation

15 Cardiovascular adaptation Aortic chemoreceptors activation of sympathetic nervous system increased cardiac output due to increased stroke volume and heart rate

16 Cardiovascular adaptation Aortic chemoreceptors activation of sympathetic nervous system increased cardiac output due to increased stroke volume and heart rate Vasoconstriction of the splanchnic circulation increased venous return and preload

17 Cardiovascular adaptation Aortic chemoreceptors activation of sympathetic nervous system increased cardiac output due to increased stroke volume and heart rate Vasoconstriction of the splanchnic circulation increased venous return and preload Preferential vasodilatation of vital organs increase in coronary circulation (up to 6X) and cerebral circulation

18 Microcirculatory adaptation Increased capillary recruitment and density increased tissue blood flow improved oxygen delivery

19 Microcirculatory adaptation Increased capillary recruitment and density increased tissue blood flow improved oxygen delivery Increased 2,3DPG, NO mediated signalling, acidosis right shift of the oxyhaemoglobin curve less oxygen affinity of haemoglobin

20 Cellular adaptation Hypoxia cellular elements stabilise HIF-α Increases expression of VEGF increased angiogenesis Increases anaerobic metabolism

21 The anaemia of inflammation could be an adaptive phenomenon

22 Undesirable effects of PRBC transfusion Increased viscosity

23 Undesirable effects of PRBC transfusion Increased viscosity Right shift of the Hb dissociation curve

24 Undesirable effects of PRBC transfusion Increased viscosity Right shift of the Hb dissociation curve Transfusion related immunomodulation (TRIM)

25 The evidence: PRBCT in ICU

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27 The TRICC trial 838 patients enrolled (critically ill with normovolemia) Assigned to one of two treatment groups Restrictive strategy Hb between 7 and 9 Liberal strategy Hb between 10 and 12

28 The TRICC trial Maintaining patients in the restrictive range ( ) Decreased the average number of RBC units transfused by 54% Decreased exposure to any RBC unit by 33%

29 Overall 30 day survival

30 Patients with Apache II score 20

31 Patients younger than 55 years

32 TRICC trial- secondary outcomes Higher rates of two cardiac events in the liberal group Myocardial infarction 2.9% vs 0.7% (p=0.02) Pulmonary oedema 10.7% vs 5.3% (p<0,01)

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34 The TRISS trial Multicentre Scandinavian trial Randomised 1005 patients with septic shock into two groups Lower threshold ( 7g/dl) Higher threshold ( 9g/dl)

35 TRISS - outcomes Median cumulative number of blood transfusions 1 unit in the lower threshold group 4 in the higher threshold group

36 TRISS - outcomes Median cumulative number of blood transfusions 1 unit in the lower threshold group 4 in the higher threshold group No transfusion required 36.1% in the lower threshold group 1.2% in the higher threshold group

37 TRISS primary outcome 90 day mortality 216 patients in the lower threshold group (43.0%) 223 in the higher threshold group (45%) Relative risk 0.94; p=0.44

38 TRISS Primary outcome subgroup analysis No significant difference in pre-specified subgroups Age > 70 or 70 Presence or absence of chronic cardiovascular disease Baseline SAPS II score > 53 or 53

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40 Traumatic Brain Injury Primary injury Secondary injury Cerebral hypoxia: hypotension, hypoxemia, (anaemia?) Fever Hypo- and hypercapnoea Hypo- and hyperglycaemia

41 Cerebral DO₂ DO₂ = CO x CaO₂ Cerebral DO₂ = Cerebral Blood Flow x CaO₂ Cerebral DO₂ = CBF x (1.34 x Hb x %saturation) + (PaO₂ x 0.003)

42 Cerebral DO₂ DO₂ = CO x CaO₂ Cerebral DO₂ = Cerebral Blood Flow x CaO₂ Cerebral DO₂ = CBF x (1.34 x Hb x %saturation) + (PaO₂ x 0.003)

43 Cerebral DO₂ in anaemia Cerebral DO₂ normally exceeds cerebral basal metabolic requirements for oxygen by a wide margin significant physiological reserve anaemia leads to increased cerebral oxygen extraction

44 Cerebral DO₂ in anaemia Anaemia leads to an increase in CBF Increase in cardiac output leads to increase in cerebral perfusion pressure Anaemia leads to increased production of nitric oxide and upregulation of cerebral β₂ receptors cerebral vasodilation Reduced haemoglobin concentration decreases viscosity increased microcirculatory flow

45 Anaemia and TBI Autoregulatory mechanisms may be unreliable in TBI Vasodilation due to anaemia may increase cerebral oedema and ICP, especially if intracranial compliance is limited Brain tissue surrounding the infarct may be more vulnerable to small drops in Hb

46 Anaemia and TBI Many studies have reported an association with reduced haemoglobin levels and worse outcomes Sekhon MS et al. Crit Care 2012, 16:R128 Retrospective cohort study of 169 patients with TBI showed a mean 7 day Hb concentration < 9g/dl was associated with increased hospital mortality

47 Anaemia and TBI Many studies have reported an association with reduced haemoglobin levels and worse outcomes Sekhon MS et al. Crit Care 2012, 16:R128 Oddo M, et al. Intensive Care Medicine 2012,38(9): Retrospective analysis of 80 patients showed that an Hb of <9 was associated with a worse neurological outcome only if associated with PbtO₂<20

48 RBC transfusion and TBI Cerebral oxygenation seems to improve slightly and inconsistently with transfusion Smith MJ et al. Crit Care Med. 2005;33(5): Prospective observational study of 35 patients with TBI/SAH before and after PRBCT An increase in PbtO₂ after was observed in 26 patients; however a decrease in PbtO₂ was observed in 9 patients

49 RBC transfusion and TBI No recent RCT has shown benefit from a liberal transfusion strategy in TBI Some have shown significant harm from a liberal transfusion strategy Warner MA, et al. J Neurosurg 2010, 113(3): Retrospective analysis of 139 patients with moderate anaemia (Hct 0,21 to 0,30) Transfusion and admission GCS were the two variables that predicted a worse neurological outcome at 6 months

50 RBC transfusion and TBI No recent RCT has shown benefit from a liberal transfusion strategy in TBI Some have shown significant harm from a liberal transfusion strategy Warner MA, et al. J Neurosurg 2010, 113(3): Salim A, et al. J Am Coll Surg 2008, 207(3): retrospective review of 1150 TBI patients showed that blood transfusion was significantly associated with higher mortality (OR 2.19) and complications (ARDS, infection, AKI)

51 RBC transfusion and TBI Issues with interpretation of the literature Inconsistent definition of severe TBI Inconsistent definition of severe anaemia Admission Hb vs mean ICU stay Hb Variable outcomes recorded - mortality, short term neurological outcomes, long term neurological outcomes

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53 The evidence for PRBCT in ICU No consideration of the effect of anaemia on the patient No consideration of the physiological effect of the PRBCT on the patient Restrictive vs liberal strategies are compared, not with usual practice Heterogeneous patient populations with varying pathophysiology

54 The evidence for PRBCT in ICU No consideration of the effect of anaemia on the patient No consideration of the physiological effect of the PRBCT on the patient Restrictive vs liberal strategies are compared, not with usual practice Heterogeneous patient populations with varying pathophysiology PRBCT may be given to the sicker patients, therefore transfusion may be a marker of disease severity

55 Conclusion Anaemia is associated with increased mortality and morbidity Anaemia may be a reflection of disease severity Anaemia may be an adaptive process

56 Conclusion Anaemia is associated with increased mortality and morbidity Anaemia may be a reflection of disease severity Anaemia may be an adaptive process Blood transfusion has unwanted effects including inefficient oxygen delivery and TRIM

57 Conclusion Anaemia is associated with increased mortality and morbidity Anaemia may be a reflection of disease severity Anaemia may be an adaptive process Blood transfusion has unwanted effects including inefficient oxygen delivery and TRIM There is a trend towards a lower transfusion trigger Studies in different populations have shown conflicting results

58 Conclusion Anaemia is associated with increased mortality and morbidity Anaemia may be a reflection of disease severity Anaemia may be an adaptive process Blood transfusion has unwanted effects including inefficient oxygen delivery and TRIM There is a trend towards a lower transfusion trigger Studies in different populations have shown conflicting results The decision to transfuse should be individualised to every patient. There should be no magic number, one size doesn t fit all

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