Anaesthesia, 1992, Volume 47, pages 962-964 CASE REPORT
Erythropoietin in a patient following multiple trauma
P. KRAUS
AND
J. LIPMAN
Summary We report on a Jehovah's Witness who had severe blood loss following major trauma. The problems of her management without blood transfusion, and with the use of recombinant human erythropoietin therapy for severe anaemia, are described. Key words Complications; trauma. Blood, haematopoiesis; erythropoietin. Organisations; Jehovah's Witnesses.
At a time when the beneficial effects of blood transfusion are being questioned [I, 2) the admission of an exsanguinated trauma patient, who happened to be a Jehovah's Witness (JW), made us consider the reasons for improving haemoglobin concentration and the alternative means which are available to us.
Case history A 45-year-old female Jehovah's Witness was admitted after a train accident in which she sustained multiple bilateral rib fractures resulting in a flail chest, a left haemopneumothorax, a severely contused left lung and a ruptured spleen. A splenectomy was performed at exploratory laparotomy during which time she received 3 1 of crystalloid (Ringer's lactate 2 1 and 5 % dextrose in saline 1 I). Postoperatively she was admitted to the Intensive Care Unit (ICU), where she was found to be conscious but pale, with poor peripheral perfusion despite a blood pressure of 140/70 mmHg and a sinus tachycardia of 120 beat.min-I. She had a nasotracheal tube in place and had marked surgical emphysema of the chest wall with a large anterior flail segment. She already had a left intercostal drain, and auscultation of the chest revealed distant heart and breath sounds. Her abdomen showed evidence of recent surgery and there were no other abnormalities on clinical examination. Her electrocardiogram showed generalised nonspecific T-wave inversion with small QRS complexes. Her chest X ray confirmed the multiple rib fractures, the severely
contused, re-expanded left lung, but in addition revealed a right-sided pneumothorax which was promptly drained. Mechanical ventilation was started and her first 24 h in the unit was marked by hypotension and a decreasing urine output, for which she received fluids, initially in the form of a synthetic colloid (Haemaccel). Dobutamine (maximum dose 20 pg.kg-'.min-' and dopamine (3 pg.kg-'.min-') were added once it was felt that her intravascular volume had been restored. Maintenance fluid was in the form of 5% dextrose in saline. By day 7 her accumulative measured fluid balance was about 13 1 positive and by day 16 it was about 23 I positive. Blood urea, electrolytes and creatinine concentrations remained normal throughout her admission. Her haemoglobin, platelets and white cell count during her time on ICU are shown in Figure I . She was given pneumococcal vaccine on day 1 and her APACHE I1 score on admission was 18. Two days after admission therapy with piperacillin and amikacin was started because of a pyrexia, increasing white cell count and worsening bilateral infiltrates on chest X ray, presumed to be the result of a nosocomial chest infection. Blood cultures and tracheal aspirates taken at that time were unhelpful. By day 4, both of her intercostal drains had been removed and she was being fed enterally. Inotropes were withdrawn by day 9, at which stage her antibiotics were also stopped. A tracheostomy was performed on day 13. From admission her haemoglobin concentration steadily decreased to a level of 3.2g.dl-' on day 16. This was
P. Kraus, FCP(SA), Senior Consultant Physician, J. Lipman, FFA(SA), Principal Consultant Anaesthetist and Head of ICU, Department of Anaesthesia and Intensive Care Unit, Baragwanath Hospital and University of Witwatersrand, PO Bertsham, 2013 South Africa. Accepted 17 April 1992. 0003-2409/92/ 1 10962 + 03 %OS.OO/O
@ 1992 The Association of Anaesthetists of G t Britain and Ireland
962
Erythropoietin in a patient following multiple trauma I L"
,
963
,
lL""
- 1000
> -
-800 -600
0 x 2
-01aJ
c
-400
- 200 I
01
' 1 " 1 1 1 ~ 1 1 " ' 1 1 1 " 1 ~ 1 1 1 1 1 1 1 1 ' ' 1 1 1 1 1 1 1 '
0
4
8
12
16
20 24 28 32 36 40 44 Days
I0
Fig. 1. Changes in haemoglobin concentration, white cell count and platelet count from admission to day 42. 0 , haemoglobin concentration g.1-I; 0 , platelet countx 109.1-'; 0,white cell count x 109.1-1.
attributed to a combination of sepsis and continuing blood loss into the left lung which had been confirmed following re-insertion of an intercostal drain on day 14. She was given daily iron, vitamin B,, and folate supplements, as well as 9 amps (4000 u each) of recombinant human erythropoietin (r-HuEPO), starting on day 7 and given over 1 week, as recommended by the manufacturers. On day 14, ceftazidime and clindamycin were started for a new chest infection and fluid drained from her left chest grew a bacillus species which was sensitive to this antibiotic combination. She responded well and the rest of her stay was marked by a protracted period of weaning from the ventilator, after which she was eventually discharged on day 24. She was seen again by one of us (P.K.) at the Respiratory Out-Patient Department 3 months following her accident, and she remains well.
Discussion Under certain circumstances adequate oxygen carrying capacity can be provided by a haemoglobin of 7 g.dl-' [I]. Although the exact critical level of haemoglobin is debatable, most intensivists would agree that this patient's haemoglobin level of 3.2 g.dl-l needed blood transfusion. Even when her ventilatory failure, resulting from a combination of a flail chest, haemothorax, contused lung, and chest infection, was corrected it was only when her haemoglobin level began to increase that she could be successfully weaned off the ventilator. Her clinical course therefore suggests the need to transfuse a patient with such severe anaemia. Since her religious beliefs precluded her from receipt of any blood products, her initial haemodynamic stabilisation was with fluids to achieve an adequate preload (as reflected by her central venous pressure) and intropes to maintain an adequate blood pressure and urine output. The policy of this unit is to givc maintenance fluids in the form of crystalloid and to administer boluses of synthetic colloid solution as the clinical situation demands. Although we cannot exclude some element of haemodilution to explain the fall in haemoglobin, normal insensitive losses are not taken into account, nor losses into the chest and abdomen which we felt were significant. Lastly, 70% of the positive
fluid balance in the first week was accounted for in the 60 h immediately after surgery, when the patient was considered to be significantly 'behind' on fluids. When it became obvious that these measures were insuficient to provide adequate oxygen delivery, permission was obtained for the compassionate use of r-HuEPO. This was the only option open to us since at present no synthetic blood preparations are available. Erythropoietin has been used in patients with renal failure, haematological disorders, in other patient populations and even in Jehovah's Witnesses [3,4]. Koestner et al. were the first to report its use in a Jehovah's Witness with trauma [3] and our patient is the first in whom r-HuEPO has been used to facilitate weaning from mechanical ventilation. We considered that the use of r-HuEPO was justified because the severe anaemia was one of the factors that prevented weaning from mechanical ventilation. Although her haemoglobin level would have eventually returned to normal the use of r-HuEPO was probably cost effective since it accelerated the process and shortened her ICU stay. As a result she developed only two nosocomial infections and avoided the many iatrogenic complications associated with prolonged mechanical ventilation. Although this patient undoubtedly benefited from stimulation of her bone marrow to increase her haemoglobin concentration, the routine transfusion of critically ill patients who are anaemic is increasingly being questioned. Haemoglobin concentration is one factor in the delivery of oxygen but recent work in both adults and children [5,6] has suggested that, although increasing the haemoglobin increases oxygen delivery, this has little effect on oxygen utilisation when compared with measures which augment the cardiac output. Although we d o not suggest that this applies to levels as low as those seen in this patient, it is of interest that two recent editorials [ I , 21 have questioned the level of haemoglobin at which transfusion is necessary. Furthermore, we have shown that with fluids, inotropic support and ventilatory support in which the Ro2 never exceeded 0.6, a patient can survive, despite an acute and chronic blood loss which resulted in a haemoglobin concentration of 3.2 g.di-I. If transfusing patients who had previously been considered to have 'too low' a concentration of haemoglobin, is not beneficial in terms of oxygen consumption are there
964
P. Kraus and J. Lipman
any deleterious effects of giving blood? Apart from the well known complications such as transfusion reactions, metabolic and coagulation disturbances and transmission of serious diseases (e.g. human immunodeficiency virus and hepatitis B & C viruses), there is the possibility that immunosuppression promotes bacterial infection [7]. In conclusion, we have presented a patient with multiple trauma who survived without blood transfusion despite severe anaemia. The contribution of r-HuEPO to her management has been highlighted. The use of autotransfusion, r-HuEPO and synthetic blood analogues may provide a means of improving aspects of oxygen delivery and utilisation and reducing immunodepression in the critically ill in the future. References [I] CANERD. Hemoglobin: how much is enough? Crirical Care Medicine 1990; 18 1046-7.
AG. T o transfuse or not to transfuse-that is the [2] GREENBURG question! Criricul Care Medicine 1990; 18 1045. [3) KOESTNER JA, NELSONLD, MORRISJA, SAFCSAKK. Use of recombinant human erythropoietin (r-HuEPO) in a Jehovah's Witness refusing transfusion of blood products: case report. Journal of Trauma 1990; 30: 1406-8. [4] HEINZ R. RElSNER R. PITTERMAN E. Erythropoietin for chemotherapy patient refusing blood transfusion. Lancet 1990; 335: 542-3. [5] DIETRICH KA, CONRADSA, HEBERTCA, LEVYGL, ROMERO MD. Cardiovascular and metabolic response to red blood cell transfusion in critically ill volume resuscitated nonsurgical patients. Critical Care Medicine 1990; 1 8 9 4 0 4 . [6] MINK RB, POLLACKM M . Effect of blood transfusion on oxygen consumption in pediatric septic shock. Criricul Cure Medicine 1990; 1 8 1087-91. [7] WAYMACK JP, YURTRW. The effects of blood transfusions on immune function. V. The effect on the inflammatory response to bacterial infections. Journal of Surgical Reseurch 1990; 48: 147-53.
Erythropoietin in a patient following multiple trauma
P. KRAUS
AND
J. LIPMAN
Summary We report on a Jehovah's Witness who had severe blood loss following major trauma. The problems of her management without blood transfusion, and with the use of recombinant human erythropoietin therapy for severe anaemia, are described. Key words Complications; trauma. Blood, haematopoiesis; erythropoietin. Organisations; Jehovah's Witnesses.
At a time when the beneficial effects of blood transfusion are being questioned [I, 2) the admission of an exsanguinated trauma patient, who happened to be a Jehovah's Witness (JW), made us consider the reasons for improving haemoglobin concentration and the alternative means which are available to us.
Case history A 45-year-old female Jehovah's Witness was admitted after a train accident in which she sustained multiple bilateral rib fractures resulting in a flail chest, a left haemopneumothorax, a severely contused left lung and a ruptured spleen. A splenectomy was performed at exploratory laparotomy during which time she received 3 1 of crystalloid (Ringer's lactate 2 1 and 5 % dextrose in saline 1 I). Postoperatively she was admitted to the Intensive Care Unit (ICU), where she was found to be conscious but pale, with poor peripheral perfusion despite a blood pressure of 140/70 mmHg and a sinus tachycardia of 120 beat.min-I. She had a nasotracheal tube in place and had marked surgical emphysema of the chest wall with a large anterior flail segment. She already had a left intercostal drain, and auscultation of the chest revealed distant heart and breath sounds. Her abdomen showed evidence of recent surgery and there were no other abnormalities on clinical examination. Her electrocardiogram showed generalised nonspecific T-wave inversion with small QRS complexes. Her chest X ray confirmed the multiple rib fractures, the severely
contused, re-expanded left lung, but in addition revealed a right-sided pneumothorax which was promptly drained. Mechanical ventilation was started and her first 24 h in the unit was marked by hypotension and a decreasing urine output, for which she received fluids, initially in the form of a synthetic colloid (Haemaccel). Dobutamine (maximum dose 20 pg.kg-'.min-' and dopamine (3 pg.kg-'.min-') were added once it was felt that her intravascular volume had been restored. Maintenance fluid was in the form of 5% dextrose in saline. By day 7 her accumulative measured fluid balance was about 13 1 positive and by day 16 it was about 23 I positive. Blood urea, electrolytes and creatinine concentrations remained normal throughout her admission. Her haemoglobin, platelets and white cell count during her time on ICU are shown in Figure I . She was given pneumococcal vaccine on day 1 and her APACHE I1 score on admission was 18. Two days after admission therapy with piperacillin and amikacin was started because of a pyrexia, increasing white cell count and worsening bilateral infiltrates on chest X ray, presumed to be the result of a nosocomial chest infection. Blood cultures and tracheal aspirates taken at that time were unhelpful. By day 4, both of her intercostal drains had been removed and she was being fed enterally. Inotropes were withdrawn by day 9, at which stage her antibiotics were also stopped. A tracheostomy was performed on day 13. From admission her haemoglobin concentration steadily decreased to a level of 3.2g.dl-' on day 16. This was
P. Kraus, FCP(SA), Senior Consultant Physician, J. Lipman, FFA(SA), Principal Consultant Anaesthetist and Head of ICU, Department of Anaesthesia and Intensive Care Unit, Baragwanath Hospital and University of Witwatersrand, PO Bertsham, 2013 South Africa. Accepted 17 April 1992. 0003-2409/92/ 1 10962 + 03 %OS.OO/O
@ 1992 The Association of Anaesthetists of G t Britain and Ireland
962
Erythropoietin in a patient following multiple trauma I L"
,
963
,
lL""
- 1000
> -
-800 -600
0 x 2
-01aJ
c
-400
- 200 I
01
' 1 " 1 1 1 ~ 1 1 " ' 1 1 1 " 1 ~ 1 1 1 1 1 1 1 1 ' ' 1 1 1 1 1 1 1 '
0
4
8
12
16
20 24 28 32 36 40 44 Days
I0
Fig. 1. Changes in haemoglobin concentration, white cell count and platelet count from admission to day 42. 0 , haemoglobin concentration g.1-I; 0 , platelet countx 109.1-'; 0,white cell count x 109.1-1.
attributed to a combination of sepsis and continuing blood loss into the left lung which had been confirmed following re-insertion of an intercostal drain on day 14. She was given daily iron, vitamin B,, and folate supplements, as well as 9 amps (4000 u each) of recombinant human erythropoietin (r-HuEPO), starting on day 7 and given over 1 week, as recommended by the manufacturers. On day 14, ceftazidime and clindamycin were started for a new chest infection and fluid drained from her left chest grew a bacillus species which was sensitive to this antibiotic combination. She responded well and the rest of her stay was marked by a protracted period of weaning from the ventilator, after which she was eventually discharged on day 24. She was seen again by one of us (P.K.) at the Respiratory Out-Patient Department 3 months following her accident, and she remains well.
Discussion Under certain circumstances adequate oxygen carrying capacity can be provided by a haemoglobin of 7 g.dl-' [I]. Although the exact critical level of haemoglobin is debatable, most intensivists would agree that this patient's haemoglobin level of 3.2 g.dl-l needed blood transfusion. Even when her ventilatory failure, resulting from a combination of a flail chest, haemothorax, contused lung, and chest infection, was corrected it was only when her haemoglobin level began to increase that she could be successfully weaned off the ventilator. Her clinical course therefore suggests the need to transfuse a patient with such severe anaemia. Since her religious beliefs precluded her from receipt of any blood products, her initial haemodynamic stabilisation was with fluids to achieve an adequate preload (as reflected by her central venous pressure) and intropes to maintain an adequate blood pressure and urine output. The policy of this unit is to givc maintenance fluids in the form of crystalloid and to administer boluses of synthetic colloid solution as the clinical situation demands. Although we cannot exclude some element of haemodilution to explain the fall in haemoglobin, normal insensitive losses are not taken into account, nor losses into the chest and abdomen which we felt were significant. Lastly, 70% of the positive
fluid balance in the first week was accounted for in the 60 h immediately after surgery, when the patient was considered to be significantly 'behind' on fluids. When it became obvious that these measures were insuficient to provide adequate oxygen delivery, permission was obtained for the compassionate use of r-HuEPO. This was the only option open to us since at present no synthetic blood preparations are available. Erythropoietin has been used in patients with renal failure, haematological disorders, in other patient populations and even in Jehovah's Witnesses [3,4]. Koestner et al. were the first to report its use in a Jehovah's Witness with trauma [3] and our patient is the first in whom r-HuEPO has been used to facilitate weaning from mechanical ventilation. We considered that the use of r-HuEPO was justified because the severe anaemia was one of the factors that prevented weaning from mechanical ventilation. Although her haemoglobin level would have eventually returned to normal the use of r-HuEPO was probably cost effective since it accelerated the process and shortened her ICU stay. As a result she developed only two nosocomial infections and avoided the many iatrogenic complications associated with prolonged mechanical ventilation. Although this patient undoubtedly benefited from stimulation of her bone marrow to increase her haemoglobin concentration, the routine transfusion of critically ill patients who are anaemic is increasingly being questioned. Haemoglobin concentration is one factor in the delivery of oxygen but recent work in both adults and children [5,6] has suggested that, although increasing the haemoglobin increases oxygen delivery, this has little effect on oxygen utilisation when compared with measures which augment the cardiac output. Although we d o not suggest that this applies to levels as low as those seen in this patient, it is of interest that two recent editorials [ I , 21 have questioned the level of haemoglobin at which transfusion is necessary. Furthermore, we have shown that with fluids, inotropic support and ventilatory support in which the Ro2 never exceeded 0.6, a patient can survive, despite an acute and chronic blood loss which resulted in a haemoglobin concentration of 3.2 g.di-I. If transfusing patients who had previously been considered to have 'too low' a concentration of haemoglobin, is not beneficial in terms of oxygen consumption are there
964
P. Kraus and J. Lipman
any deleterious effects of giving blood? Apart from the well known complications such as transfusion reactions, metabolic and coagulation disturbances and transmission of serious diseases (e.g. human immunodeficiency virus and hepatitis B & C viruses), there is the possibility that immunosuppression promotes bacterial infection [7]. In conclusion, we have presented a patient with multiple trauma who survived without blood transfusion despite severe anaemia. The contribution of r-HuEPO to her management has been highlighted. The use of autotransfusion, r-HuEPO and synthetic blood analogues may provide a means of improving aspects of oxygen delivery and utilisation and reducing immunodepression in the critically ill in the future. References [I] CANERD. Hemoglobin: how much is enough? Crirical Care Medicine 1990; 18 1046-7.
AG. T o transfuse or not to transfuse-that is the [2] GREENBURG question! Criricul Care Medicine 1990; 18 1045. [3) KOESTNER JA, NELSONLD, MORRISJA, SAFCSAKK. Use of recombinant human erythropoietin (r-HuEPO) in a Jehovah's Witness refusing transfusion of blood products: case report. Journal of Trauma 1990; 30: 1406-8. [4] HEINZ R. RElSNER R. PITTERMAN E. Erythropoietin for chemotherapy patient refusing blood transfusion. Lancet 1990; 335: 542-3. [5] DIETRICH KA, CONRADSA, HEBERTCA, LEVYGL, ROMERO MD. Cardiovascular and metabolic response to red blood cell transfusion in critically ill volume resuscitated nonsurgical patients. Critical Care Medicine 1990; 1 8 9 4 0 4 . [6] MINK RB, POLLACKM M . Effect of blood transfusion on oxygen consumption in pediatric septic shock. Criricul Cure Medicine 1990; 1 8 1087-91. [7] WAYMACK JP, YURTRW. The effects of blood transfusions on immune function. V. The effect on the inflammatory response to bacterial infections. Journal of Surgical Reseurch 1990; 48: 147-53.
