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That 18.5% of the critically ill patients reported in JAMA died
within 28 days in the group having received blood transfusions and only
10.1% died in the group not receiving blood transfusion
(chi squared=50.1; P<0.001) is not surprising (1).
An inadequacy of mitochondrial oxidative phosphorylation, revealed in
the development of a gastric intramucosal acidosis from unreversed ATP
hydrolysis, appears to be the primary determinant of organ dysfunctions
and failures and death in the critically ill (2,3). The tissue acidosis is
presumably a reflection of the degree of failure of the protonmotive force
that drives the resynthesis of ATP, Mitchell having being awarded the
Nobel prize for his identification of the importance of the protonmotive
force in ATP synthesis (4).
Normovolaemic haemodilution in patients having cardiac surgery caused
a fall in gastric intramucosal pH in one study (5) but did not appear to
impair tissue perfusion or oxygen consumption and did not cause a fall in
gastric intramucosal pH in other studies (6,7). Replacing red blood cells
with Perflubron, a perfluorocarbon emulsion, prevented the fall in
gastric intramucosal pH in the first of these studies (5).
Red cell transfusion does not increase oxygen consumption in septic
patients in an intensive care unit (8). Transfusing red blood cells in
septic patients may, however, induce a fall in gastric intramucosal pH
(9,10). In those patients receiving blood that had been stored for more
than 15 days, the gastric intramucosal pH consistently decreased following
the red blood cell transfusion (10). The authors postulated that the
poorly deformable transfused red blood cells cause micro-circulatory
occlusion in some organs, which may lead to tissue ischaemia in some
organs. Vincent and Peres-Bota suggested that packed red blood cell
transfusions may contribute to immunosuppression and may not improve
oxygenation to the desired extent because of variation in storage and
preservation techniques (1). It is likely that the release of cytokines,
induced either by tissue injury, red blood transfusions, sepsis, or the
development of an intramucosal acidosis in the gut and presumably
accompanying free radical release (3), cause a fall in gastric
intramucosal pH by uncoupling mitochondrial oxidative phosphorylation
(11). The translocation of bacterial endotoxin in the gut and especially
in the colon might be the most important cause of cytokine release in the
critically ill because of their putative ability to uncouple
mitochondrial oxidative phosphorylation (12). ). An impairment in oxygen
uptake and utilisation is certainly a major problem in the management of
the critically ill.
Vincent and Peres-Bota also suggest that the red cells may not
always improve tissue oxygenation to the desired extent in the critically
ill because of variation in storage and preservation techniques (1).
Sibbald and Marik’s data certainly suggest that red blood cell
transfusions should be restricted to blood less than ten days old if it
is to improve the adequacy of tissue oxygenation, that is of
mitochondrial oxidative phosphorylation (10). Vincent and Peres-Bota
further suggest giving erythropoietin as an alternative to red cell
transfusions in correcting anaemia and hypoxia in critically ill patients.
Eliminating the source of gut endotoxin by gut lavage, with the intention
of preventing the uncoupling of mitochondrial oxidative phosphorylation,
is another therapeutic option to consider(12). Recent evidence from the
management of fulminant amoebic colitis suggests this might be particlarly
effective form of therapy(13)
One would have thought that red blood transfusions were
unquestionably beneficial in patients in severe haemorrhagic shock but
this is not necessarily the case (13). Mattox and his group have shown
that restricting transfusions of all types before surgery for traumatic
injuries improves outcome from haemorrhagic shock. Furthermore experience
with organ preservation for transplantation suggests that organ
preservation fluids such as UW or possibly better Celsior, which has a
lower concentration of potassium, might be far more effective in
resuscitating patients than red blood cells. If the purpose is to increase
oxygen carrying capacity Perflubron, a perfluorocarbon emulsion, might be
the best solution to use (5). It which case Perflubron might also be
preferable to red blood cell transfusions for amaemia in the critically
ill even if they are less than ten days old. The rheological benefits
likely to be provided by Perflubron is especially appealing in septic
patients in whom mircovascular sludging might be an important cause of
impaired tissue perfusion.
1. Josefson D. Blood transfusions may increase the risk of death in
critically ill patients. BMJ 2002;325:735 ( 5 October )
3. Fiddian-Green RG. Monitoring of tissue pH: the critical
measurement.
Chest. 1999 Dec;116(6):1839-41
4. Reid RA, Moyle J, Mitchell P. Synthesis of adenosine triphosphate by a
protonmotive force in rat liver mitochondria. Nature. 1966 Oct
15;212(59):257-8
5. Frumento RJ, Mongero L, Naka Y, Bennett-Guerrero E. Preserved
gastric tonometric variables in cardiac surgical patients administered
intravenous perflubron emulsion. Anesth Analg. 2002 Apr;94(4):809-14,
table of contents.
6. Bacher A, Mayer N, Rajek AM, Haider W. Acute normovolaemic
haemodilution does not aggravate gastric mucosal acidosis during cardiac
surgery. Intensive Care Med. 1998 Apr;24(4):313-21.
7. Santoso JT, Hannigan EV, Levine L, Solanki DR, Mathru M. Effect of
hemodilution on tissue perfusion and blood coagulation during radical
hysterectomy. Gynecol Oncol. 2001 Aug;82(2):252-6.
8. Frumento RJ, Mongero L, Naka Y, Bennett-Guerrero E..Red blood cell
transfusion does not increase oxygen consumption in critically ill septic
patients.
Crit Care. 2001 Dec;5(6):362-7.
9. Silverman HJ, Tuma P. Effects of dobutamine infusions and packed red
blood cell transfusions.
Chest. 1992 Jul;102(1):184-8.
10. Marik PE, Sibbald WJ. Effect of stored-blood transfusion on oxygen
delivery in patients with sepsis.
JAMA. 1993 Jun 16;269(23):3024-9.Gastric tonometry in patients with
sepsis.
11. Lassus P, Opitz-Araya X, Lazebnik Y. Requirement for caspase-2 in
stress-induced apoptosis before mitochondrial permeabilization. Science.
2002 Aug 23;297(5585):1352-4.
12. Fink MP, Fiddian-Green RG. Care of the gut in the critically ill.
In Marston A, Bulkley GB, Fiddian Green RG, Haglund UH, eds. Splanchnic
ischemia and multiple organ failure. London: Edward Arnold, 1989.
13. Fiddian-Green RG. Colonic lavage for severe haemorrhagic shock?
bmj.com/cgi/eletters/325/7366/674/b#25839, 27 Sep 2002
Mitochondrial considerations
That 18.5% of the critically ill patients reported in JAMA died
within 28 days in the group having received blood transfusions and only
10.1% died in the group not receiving blood transfusion
(chi squared=50.1; P<0.001) is not surprising (1).
An inadequacy of mitochondrial oxidative phosphorylation, revealed in
the development of a gastric intramucosal acidosis from unreversed ATP
hydrolysis, appears to be the primary determinant of organ dysfunctions
and failures and death in the critically ill (2,3). The tissue acidosis is
presumably a reflection of the degree of failure of the protonmotive force
that drives the resynthesis of ATP, Mitchell having being awarded the
Nobel prize for his identification of the importance of the protonmotive
force in ATP synthesis (4).
Normovolaemic haemodilution in patients having cardiac surgery caused
a fall in gastric intramucosal pH in one study (5) but did not appear to
impair tissue perfusion or oxygen consumption and did not cause a fall in
gastric intramucosal pH in other studies (6,7). Replacing red blood cells
with Perflubron, a perfluorocarbon emulsion, prevented the fall in
gastric intramucosal pH in the first of these studies (5).
Red cell transfusion does not increase oxygen consumption in septic
patients in an intensive care unit (8). Transfusing red blood cells in
septic patients may, however, induce a fall in gastric intramucosal pH
(9,10). In those patients receiving blood that had been stored for more
than 15 days, the gastric intramucosal pH consistently decreased following
the red blood cell transfusion (10). The authors postulated that the
poorly deformable transfused red blood cells cause micro-circulatory
occlusion in some organs, which may lead to tissue ischaemia in some
organs. Vincent and Peres-Bota suggested that packed red blood cell
transfusions may contribute to immunosuppression and may not improve
oxygenation to the desired extent because of variation in storage and
preservation techniques (1). It is likely that the release of cytokines,
induced either by tissue injury, red blood transfusions, sepsis, or the
development of an intramucosal acidosis in the gut and presumably
accompanying free radical release (3), cause a fall in gastric
intramucosal pH by uncoupling mitochondrial oxidative phosphorylation
(11). The translocation of bacterial endotoxin in the gut and especially
in the colon might be the most important cause of cytokine release in the
critically ill because of their putative ability to uncouple
mitochondrial oxidative phosphorylation (12). ). An impairment in oxygen
uptake and utilisation is certainly a major problem in the management of
the critically ill.
Vincent and Peres-Bota also suggest that the red cells may not
always improve tissue oxygenation to the desired extent in the critically
ill because of variation in storage and preservation techniques (1).
Sibbald and Marik’s data certainly suggest that red blood cell
transfusions should be restricted to blood less than ten days old if it
is to improve the adequacy of tissue oxygenation, that is of
mitochondrial oxidative phosphorylation (10). Vincent and Peres-Bota
further suggest giving erythropoietin as an alternative to red cell
transfusions in correcting anaemia and hypoxia in critically ill patients.
Eliminating the source of gut endotoxin by gut lavage, with the intention
of preventing the uncoupling of mitochondrial oxidative phosphorylation,
is another therapeutic option to consider(12). Recent evidence from the
management of fulminant amoebic colitis suggests this might be particlarly
effective form of therapy(13)
One would have thought that red blood transfusions were
unquestionably beneficial in patients in severe haemorrhagic shock but
this is not necessarily the case (13). Mattox and his group have shown
that restricting transfusions of all types before surgery for traumatic
injuries improves outcome from haemorrhagic shock. Furthermore experience
with organ preservation for transplantation suggests that organ
preservation fluids such as UW or possibly better Celsior, which has a
lower concentration of potassium, might be far more effective in
resuscitating patients than red blood cells. If the purpose is to increase
oxygen carrying capacity Perflubron, a perfluorocarbon emulsion, might be
the best solution to use (5). It which case Perflubron might also be
preferable to red blood cell transfusions for amaemia in the critically
ill even if they are less than ten days old. The rheological benefits
likely to be provided by Perflubron is especially appealing in septic
patients in whom mircovascular sludging might be an important cause of
impaired tissue perfusion.
1. Josefson D. Blood transfusions may increase the risk of death in
critically ill patients. BMJ 2002;325:735 ( 5 October )
2. Fiddian-Green RG. Gastric intramucosal pH, tissue oxygenation and
acid-base balance.
Br J Anaesth. 1995 May;74(5):591-606. Review.
3. Fiddian-Green RG. Monitoring of tissue pH: the critical
measurement.
Chest. 1999 Dec;116(6):1839-41
4. Reid RA, Moyle J, Mitchell P. Synthesis of adenosine triphosphate by a
protonmotive force in rat liver mitochondria. Nature. 1966 Oct
15;212(59):257-8
5. Frumento RJ, Mongero L, Naka Y, Bennett-Guerrero E. Preserved
gastric tonometric variables in cardiac surgical patients administered
intravenous perflubron emulsion. Anesth Analg. 2002 Apr;94(4):809-14,
table of contents.
6. Bacher A, Mayer N, Rajek AM, Haider W. Acute normovolaemic
haemodilution does not aggravate gastric mucosal acidosis during cardiac
surgery. Intensive Care Med. 1998 Apr;24(4):313-21.
7. Santoso JT, Hannigan EV, Levine L, Solanki DR, Mathru M. Effect of
hemodilution on tissue perfusion and blood coagulation during radical
hysterectomy. Gynecol Oncol. 2001 Aug;82(2):252-6.
8. Frumento RJ, Mongero L, Naka Y, Bennett-Guerrero E..Red blood cell
transfusion does not increase oxygen consumption in critically ill septic
patients.
Crit Care. 2001 Dec;5(6):362-7.
9. Silverman HJ, Tuma P. Effects of dobutamine infusions and packed red
blood cell transfusions.
Chest. 1992 Jul;102(1):184-8.
10. Marik PE, Sibbald WJ. Effect of stored-blood transfusion on oxygen
delivery in patients with sepsis.
JAMA. 1993 Jun 16;269(23):3024-9.Gastric tonometry in patients with
sepsis.
11. Lassus P, Opitz-Araya X, Lazebnik Y. Requirement for caspase-2 in
stress-induced apoptosis before mitochondrial permeabilization. Science.
2002 Aug 23;297(5585):1352-4.
12. Fink MP, Fiddian-Green RG. Care of the gut in the critically ill.
In Marston A, Bulkley GB, Fiddian Green RG, Haglund UH, eds. Splanchnic
ischemia and multiple organ failure. London: Edward Arnold, 1989.
13. Fiddian-Green RG. Colonic lavage for severe haemorrhagic shock?
bmj.com/cgi/eletters/325/7366/674/b#25839, 27 Sep 2002
Competing interests: No competing interests