Transfusion practice in major obstetric haemorrhage: lessons from trauma

I. Saule, N. Hawkins

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3. Khan AK, Nair CK. Clinical, diagnostic and management perspectives of aortic dissection. Chest 2002;122:311–28. 4. Immer FF, Bansi AG, Immer-Bansi AS, et al. Aortic dissection in pregnancy: analysis of risk factors and outcome. Ann Thorac Surg 2003;76:309–14. 5. Lewis S, Ryder I, Lovell AT. Peripartum presentation of an acute aortic dissection. Br J Anaesth 2005;94:496–9. 6. Wahlers T, Laas J, Alken A, Borst HG. Repair of acute type A aortic dissection after cesarean section in the thirty-ninth week of pregnancy. J Thorac Cardiovasc Surg 1994;107:314–5. 7. Evans PJ, Rajappan K, Stocks GM. Cardio-respiratory symptoms during pregnancy—not always pulmonary embolism. Int J Obstet Anesth 2006;15:320–4. 8. Pumphrey CW, Fay T, Weir I. Aortic dissection during pregnancy. Br Heart J 1986;55:106–8. 9. Nasiell J, Norman M, Lindqvist PG, Malmstedt J, Bottinga R, Blennow M. Aortic dissection in pregnancy: a life-threatening disease and a diagnosis worth considering. Acta Obstet Gynecol Scand 2009;88:1167–70. 10. Kolesar A, Sabol F, Luczy J, Bajmoczi M. Use of left ventricle assist device in a pregnant woman with acute aortic and coronary dissections. Interact Cardiovasc Thorac Surg 2010;11:194–5. 11. Papatsonis DN, Heetkamp A, van den Hombergh C, et al. Acute type A aortic dissection complicating pregnancy at 32 weeks: surgical repair after cesarean section. Am J Perinatol 2009;26:153–7. 12. Shihata M, Pretorius V, MacArthur R. Repair of an acute type A aortic dissection combined with an emergency cesarean section in

13.

14.

15.

16.

17.

18.

19.

20.

a pregnant woman. Interact Cardiovasc Thorac Surg 2008;7:938–40. Omar AR, Goh WP, Lim YT. Peripartum acute anterior ST segment elevation myocardial infarction: an uncommon presentation of acute aortic dissection. Ann Acad Med Singapore 2007;36:854–6. Fabricius AM, Autschbach R, Doll N, Mohr W. Acute aortic dissection during pregnancy. Thorac Cardiovasc Surg 2001;49:56–7. Ecknauer E, Schmidlin D, Jenni R, Schmid ER. Emergency repair of incidentally diagnosed ascending aortic aneurysm immediately after caesarean section. Br J Anaesth 1999;83:343–5. Zeebregts CJ, Schepens MA, Hameeteman TM, Morshuis WJ, de la Riviere AB. Acute aortic dissection complicating pregnancy. Ann Thorac Surg 1997;64:1345–8. Spittell PC, Spittell Jr JA, Joyce JW, et al. Clinical features and differential diagnosis of aortic dissection: experience with 236 cases (1980 through 1990). Mayo Clin Proc 1993;68:642–51. Erbel R, Alfonso F, Boileau C, et al. Diagnosis and management of aortic dissection – Recommendations of the Task Force on Aortic Dissection, European Society of Cardiology. Eur Heart J 2001;22:1642–81. Mancini MC. Medscape eMedicine, Aortic Dissection. http:// www.emedicine.medscape.com/article/425118-overview [accessed 5.8.2011]. Erbel R, Engberding R, Daniel W, et al. Echocardiography in diagnosis of aortic dissection. Lancet 1989;1(8636):457–61.



0959-289X/$-see front matter c 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.ijoa.2011.09.006

Transfusion practice in major obstetric haemorrhage: lessons from trauma I. Saule, N. Hawkins Department of Anaesthesia, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK ABSTRACT The management of massive haemorrhage with blood products is changing as evidence arrives from civilian and military trauma. Rapid early replacement of coagulation factors and platelets is now becoming central to improving outcome, usually given in higher ratios with respect to red cell units than previously recommended and using empiric transfusion based on clinical rather than laboratory parameters. The management of three cases of major obstetric haemorrhage based on these principles is presented. Packed red blood cells, fresh frozen plasma, platelets and cryoprecipitate were transfused in the ratios 5:2:2:1, 4.5:1:1:1 and 4.5:2:1:1. Each patient had acceptable full blood count and coagulation results after surgery and all made an uneventful recovery. These outcomes support the opinion that major obstetric haemorrhage can be managed in a similar fashion to blood loss in trauma. Recommendations from the Association of Anaesthetists of Great Britain and Ireland, and the UK National Patient Safety Agency should be considered during major obstetric haemorrhage. c 2011 Elsevier Ltd. All rights reserved.



Keywords: Obstetric; Haemorrhage; Blood loss; Transfusion; Clotting factors; Transfusion ratio; Military trauma

Accepted September 2011 Correspondence to: I. Saule, Department of Anaesthesia, Nottingham University Hospitals NHS Trust, City Hospital Campus, Hucknall Rd, Nottingham NG5 1PB, UK. E-mail address: [email protected]

Introduction Major obstetric haemorrhage is defined as a blood loss of 2500 mL or more, transfusion of five units of red

80 blood cells or treatment of a coagulopathy.1,2 Obstetric resuscitation often starts with administration of clear intravenous fluids and packed red blood cells (pRBC), following which the use of clotting products and platelets is considered, often guided by coagulation studies that delay treatment.3 The UK National Patient Safety Agency (NPSA) recommends monitoring laboratory blood tests during massive transfusion, but also that administration of blood and blood products should not be delayed while awaiting results.1,3–5 Resuscitation of bleeding patients with crystalloid, colloid and plasma-poor pRBC at the same time that clotting factors are being consumed results in the concentration of plasma coagulation factors falling to <40%, and typically occurs before 10 units of pRBC have been given.6 Disseminated intravascular coagulopathy in obstetric haemorrhage can also occur early, especially if haemorrhage is not treated rapidly. Early treatment of massive haemorrhage after trauma using fresh frozen plasma (FFP) and pRBC in a 1:1 ratio, current practice in US and British military, is thought to improve survival.6–11 Military guidelines for haemorrhagic shock also recommend administration of platelets in a 1:1 ratio with pRBC.7–9,11 Prevention of coagulopathy should be better than its treatment and requires anticipation.6 Some authors advise that replacement of clotting factors should be made on clinical grounds, rather than based on laboratory results.4,7,11,12 The Association of Anaesthetists of Great Britain and Ireland (AAGBI) guideline recommends early infusion of FFP (15 mL/kg) to prevent haemostatic failure and may need to be started if a senior clinician anticipates massive haemorrhage.13 This guideline emphasises the importance of preventing haemostatic failure because, once established, standard regimens of FFP infusion are likely to be inadequate and larger volumes will be required with greater risk to the patient and cost implications for the hospital.13 For massive obstetric haemorrhage, a ratio of 6:4:1 for pRBC:FFP:platelets has been suggested. If bleeding continues after initial treatment, consideration should be given to increasing the amount of FFP to give a ratio of 4:4:1.5 Point-of-care tests can measure haemoglobin concentration and the coagulation profile, and may guide blood product replacement following initial resuscitation. Three cases of major obstetric haemorrhage treated using these principles are described. In each case the patients’ blood results (Tables 1–3) and fluid replacement (Table 4) are listed.

Case 1 A 26-year-old, healthy, nulliparous woman was scheduled for elective caesarean delivery at term due to a transverse fetal position. Her pre-operative haemoglobin (Hb) was 11.7 g/dL. Monitoring of non-invasive blood pres-

Transfusion practice Table 1

Case 1 blood results Preoperative

Arterial pH Arterial base excess (mmol/L) Haemoglobin (g/dL) Platelets (·109/L) Prothrombin time (s) APTT (s) Thrombin time (s) Fibrinogen (g/L)

End of surgery

24 h post-op

7.36 3.6 11.7

10.6 165 8 25 14 2.3

10.0 130 9 27 14 n/a

End of surgery

24 h post-op

APTT: activated partial thromboplastin time.

Table 2

Case 2 blood results Preoperative

Arterial pH Arterial base excess (mmol/L) Haemoglobin (g/dL) Platelets (·109/L) Prothrombin time (s) APTT (s) Thrombin time (s)

7.42 3.9 10.7 212

7.5 108 10 34 14

8.4 109 10 32 13

APTT: activated partial thromboplastin time.; Fibrinogen not measured.

sure (BP), electrocardiogram (ECG) and oxygen saturation were started. Compound sodium lactate 1000 mL was infused and spinal anaesthesia with hyperbaric bupivacaine 12.5 mg and diamorphine 500 lg at the L3-4 interspace produced surgical anaesthesia to T4. A phenylephrine infusion (1 mg/50 mL at 50 mL/h) maintained normotension. Delivery of the fetus was difficult, necessitating an inverted uterine T-incision and administration of intravenous terbutaline 125 lg. Following delivery, two 5-IU boluses followed by an infusion of 10 IU/h of oxytocin were given. Uterine atony persisted with continued bleeding. Six doses of intramuscular carboprost 250 lg were administered together with three doses of intravenous ergometrine 500 lg. Forty minutes after delivery of the baby, the woman’s Hb concentration, measured by a Hemocue Hb 201 (Hemocue AB, Angelholm, Sweden) was 7.6 g/dL. According to institutional practice, blood and blood products were given as per the trauma protocol of our hospital, and were transfused in the order: pRBC, FFP, platelets, cryoprecipitate and recombinant factor VIIa (rFVIIa), their use guided by on-going bleeding. A dose of rFVIIa (90 lg/kg) was administered 70 min after product replacement began and after a total of 5 units of pRBC, 2 units of FFP, 2 units of platelets and 1 unit of cryoprecipitate had been given. The patient also received compound sodium lactate

I. Saule, N. Hawkins Table 3

81

Case 3 blood results Before delivery

Arterial pH Arterial base excess (mmol/L) Haemoglobin (g/dL) Platelets (·109/L) Prothrombin time (s) APTT (s) Thrombin time (s) Fibrinogen (g/L)

Induction of anaesthesia

10.6 287

3.7 10 23 10

End of surgery 7.29 10.6 8.5 139

Recovery

24 h post-op

7.8

7.5 128 10 31 12 3.8

8 27 13 3.3

APTT: activated partial thromboplastin time.

Table 4

Blood loss, fluid and blood product replacement

Blood loss (mL) Compound sodium lactate (mL) Normal saline (mL) Gelofusine (mL) pRBC (units) FFP (units) Platelets (units) Cryoprecipitate (units) rFVIIa (mg) Cell salvaged blood (mL)

Case 1

Case 2

Case 3

5500 4000 – 500 5 2 2 1 9

7500 7500 – – 9 2 2 2 7 600

4000a 1500 1000 1000 9 5 2 2 7

pRBC: packed red blood cells; FFP: fresh frozen plasma; rFVIIa: recombinant factor VIIa.a Operative blood loss only; preoperative blood loss not recorded.;

4000 mL, Gelofusine 500 mL and calcium chloride 2.5 mmol. All fluids were warmed. After 120 min, general anaesthesia was induced for patient comfort and maintained with sevoflurane in an oxygen and nitrous oxide mix. Throughout surgery systolic BP remained between 90-140 mmHg, heart rate 60–110 beats/min in sinus rhythm with oxygen saturation 96– 100%. A warm air blower (Bair Hugger 750, Arizant Healthcare Inc, Eden Prairie, MN, USA) was used. Propofol was substituted for sevoflurane near the end of surgery to limit effects on uterine contraction. Surgery lasted 220 min and estimated blood loss was 5500 mL. The patient was woken, her trachea was extubated and she was transferred to the obstetric high-dependency unit (HDU), where one further unit of pRBC was administered 7 h after the operation. The woman made an uneventful recovery and was discharged home three days later.

Case 2 A 37-year-old healthy woman presented for elective caesarean delivery at 36 weeks of gestation with an anterior grade-4 placenta praevia. She had undergone two previous caesarean deliveries. Two 14-gauge intravenous cannulae and an epidural catheter were inserted. In the radiology department bilateral intravascular balloon catheters were placed in the

anterior branches of the internal iliac arteries. In the operating room (OR), epidural anaesthesia using 17 mL of a mixture containing equal volumes of 0.5% bupivacaine and 2% lidocaine with 1:200 000 adrenaline and sodium bicarbonate 2 mL resulted in a block to T4. Intravenous infusion of warmed compound sodium lactate and active patient warming were started, and a red blood cell salvage pump (Fresenius HemoCare, Germany) was prepared. Following delivery of a live baby through the placenta, a 5-IU bolus of oxytocin and infusion of 10 IU/h were given and the internal iliac artery balloons inflated. Massive bleeding occurred during attempted removal of the adherent placenta. A Bakri balloon was inserted and inflated, and red cell salvage started. After 5 units of pRBC, 2 units each of FFP, platelets and cryoprecipitate, rFVIIa 90 lg/kg was given and 600 mL of salvaged blood was returned to the patient. Further bleeding necessitated hysterectomy, and the administration of a further 4 units of pRBC. Epidural anaesthesia was maintained with additional boluses of the initial injectate. Surgery lasted 190 min and estimated blood loss was 7500 mL. Cardiovascular variables were stable and the patient was transferred to the obstetric HDU where a further unit of pRBC was given. Blood results are shown in Table 2. Recovery was uneventful and the patient was discharged home five days later.

Case 3 A 26-year-old woman, in her second pregnancy at term, had a prolonged labour with a normal vaginal delivery, but sustained perineal tears. During the repair she became haemodynamically unstable. Fluid resuscitation started with Gelofusine 1000 mL and crystalloid 1500 mL. Hemocue showed a Hb concentration of 5.4 g/dL and 2 units O-Rh negative, uncrossmatched blood were given during transfer to the OR. General anaesthesia was induced with a modified rapid sequence technique using ketamine and suxamethonium, and maintained with sevoflurane in oxygen and air. Standard non-invasive monitoring and active patient warming were used. Intra-operatively, after transfusion of 6 units pRBC, 4 units of FFP, 1 unit of platelets and 2 units of cryopre-

82 cipitate, rFVIIa 90 lg/kg and calcium chloride 2.5 mmol were given. Blood gas analysis 40 min before emergence showed a metabolic acidosis (Table 3). Anaesthesia and surgery lasted 180 min with an estimated intraoperative blood loss of 4000 mL; pre-operative blood loss was not recorded. Cardiovascular variables were stable and the patient was transferred to the HDU, where a further 2 units of pRBC, 2 units of FFP and 1 unit of platelets were given. The patient made a good recovery and was discharged home three days later.

Discussion Transfusion of blood and blood products in trauma and major haemorrhage is changing as a result of experience in military medicine. Current trauma practice advises early use of pRBC, platelets and clotting products in high ratios. Resuscitation in obstetric haemorrhage is similar to that in trauma as both aim to stop bleeding, maintain efficient oxygen delivery and prevent development of the ‘‘lethal triad’’ of acidosis, coagulopathy and hypothermia.3,5,14,15 However, in the obstetric patient the amount of tissue trauma and contamination is less, and obstetric haemorrhage usually occurs in a controlled environment where treatment and medical attention are rapidly available.16 Fibrinogen concentrations are also greater in pregnancy; the optimal post-transfusion fibrinogen concentration has been suggested as 1.0–2.0 g/L.3 The high ratios of pRBC to coagulation products that are recommended for other types of trauma may therefore not be required in the obstetric patient, whereas greater replacement of fibrinogen may be necessary. There is evidence to support 1:1:1 ratios of pRBC:FFP:platelets in trauma, but less so in obstetrics.3,7–11,17–23 Transfusion guidelines from the AAGBI suggest that 1:1:1 pRBC:FFP:platelets ratios should be reserved for the most severely traumatised patients.13 In the three cases reported, the decision to transfuse platelets and clotting products was based on clinical grounds rather than on laboratory results and made according to local trauma management guidelines. Administration of pRBC was based on vital signs, blood loss and point-of-care Hb analysis and ratios of pRBC:FFP of 1.8–4.5 and pRBC:platelets of 2.5–4.5 were used. Tables 1–3 show that by the end of surgery all three patients had adequate Hb concentrations, platelet numbers and coagulation profiles. Cryoprecipitate was given to all three patients to increase fibrinogen concentrations.3 In Case 1 a ratio of pRBC:cryoprecipitate of 5.5:1 resulted in a fibrinogen concentration of 2.3 g/L on emergence from anaesthesia; in Case 2 a ratio of 2:1 resulted in a fibrinogen concentration of 3.3 g/L in the recovery unit. This suggests that high pRBC:cryoprecipitate ratios may not be required. Maintenance of a platelet count between 50–100 · 109/L has been suggested, although should only be used

Transfusion practice as a guide in conjunction with the patient’s clinical condition.3 pRBC:platelets ratios of 5:2 and 5:1 have been described with good results.3,10 Case 1 in this series received pRBC and platelets in a ratio of 2.5:1, resulting in a platelet count of 165 · 109/L on emergence from anaesthesia; both other cases received a ratio of 4.5:1, resulting in platelet counts of 108 and 139 · 109/L on emergence. These results are similar to other reports that attempted to maintain the platelet count >100 · 109/L.3,10 Consensus guidelines in the literature suggest that rFVIIa should be considered before hysterectomy if haemostatic failure and haemorrhage continue despite optimal blood product replacement and obstetric management.3,14,24,25 Arterial thrombosis is a potential complication of rFVIIa use, but has not been reported in a case series of 15 patients.24 Its safety in the obstetric population is unproven, and it carries a significant cost implication. The use thromboelastography and thromboelastometry to guide optimum ratios of blood product replacement during obstetric haemorrhage may be limited by time during the initial resuscitation phase, and there is limited familiarity with their use in obstetrics.1,3,5,16,23 The financial implications of changing transfusion practice are unclear due to uncertainties in the optimal ratios of pRBC, platelets, FFP and cryoprecipitate, and of the place of rFVIIa. If early administration of pRBC, platelets and clotting products is used to avoid or limit coagulopathy, it is our contention that the total quantity of blood and clotting products administered may be less, with reductions in critical care and hospital stay, patient morbidity and mortality, resulting in financial savings and preservation of blood and clotting product stocks. The three cases presented demonstrate that early treatment with pRBC and blood products may reduce the risk of coagulopathy, and that the high ratios of pRBC to other blood products currently advised in trauma guidelines may not be required.

References 1. Wise A, Clark V. Strategies to manage major obstetric haemorrhage. Curr Opin Anaesthesiol 2008;21:281–7. 2. Brace V, Kernaghan D, Penney G. Learning from adverse clinical outcomes: major obstetric haemorrhage in Scotland, 2003–05. BJOG 2007;114:1388–96. 3. Mercier JF, Bonnet MP. Use of clotting factors and other prohemostatic drugs for obstetric hemorrhage. Curr Opin Anaesthesiol 2010;23:310–6. 4. National Patient Safety Agency, Rapid Response Report NPSA/ 2010/017. The transfusion of blood and blood components in an emergency, October 2010. 5. Burtelow M, Riley E, Druzin M, Fontaine M, Viele M, Goodnough LT. How we treat: management of life-threatening primary postpartum haemorrhage with a standardized massive transfusion protocol. Transfusion 2007;47:1564–72. 6. Ketchum L, Hess JR, Hiippala S. Indications for early fresh frozen plasma, cryoprecipitate, and platelet transfusion in trauma. J Trauma 2006;60:S51–8.

A.L. Hoefnagel, R. Wissler 7. Jansen O, Thomas R, Loudon A, Brooks A. Damage control resuscitation for patients with major trauma. BMJ 2009;338:1436–40. 8. Holcomb JB, Jenkins D, Rhee P, et al. Damage control resuscitation: directly addressing the early coagulopathy of trauma. J Trauma 2007;62:307–10. 9. Borgman MA, Spinella PC, Perkins JG, et al. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma 2007;63: 805–13. 10. Gunter OL, Au BK, Isbell JM, Mowery NT, Young PP, Cotton BA. Optimizing outcomes in damage control resuscitation: identifying blood product ratios associated with improved survival. J Trauma 2008;65:527–34. 11. Kirkman E, Watts S, Hodgetts T, Mahoney P, Rawlinson S, Midwinter M. A proactive approach to the coagulopathy of trauma: the rationale and guidelines for treatment. J R Army Med Corps 2008;153:302–6. 12. Hodgetts TJ, Mahoney PF, Kirkman E. Damage control resuscitation. J R Army Med Corps 2007;153:299–300. 13. Working Party Association of Anaesthetists of Great Britain and Ireland (AAGBI). Guidelines. Blood transfusion and the anaesthetist: management of massive haemorrhage. Anaesthesia 2010;65:1153–61. 14. Mercier FJ, Van de Velde M. Major obstetric haemorrhage. Anesthesiol Clin 2008;26:53–66. 15. Mukherjee S, Arulkumaran S. Post-partum haemorrhage. Obstet Gynaecol Reprod Med 2009;19(5):121–6. 16. Ickx BE. Fluid and blood transfusion management in obstetrics. Eur J Anaesthesiol 2010;27:1031–5.

83 17. Gunter OL, Brigham KA, Isbell JM, Mowery NT, Young PP, Cotton BA. Optimizing outcomes in damage control resuscitation: identifying blood product ratios associated with improved survival. J Trauma 2008;65:527–34. 18. Sperry JL, Ochoa JB, Gunn SR, et al. An FFP:PPRBC Transfusion ratio P 1:1.5 is associated with a lower risk of mortality after massive transfusion. J Trauma 2008;65:986–93. 19. Blood transfusion in Obstetrics. RCOG. Green-top Guideline No. 47. December 2007. accessed July 2011. 20. Malone DL, Hess JR, Fingergut A. Massive transfusion protocols around the globe and a suggestion for a common massive transfusion protocol. J Trauma 2006;60:S91–6. 21. MacLeod JBA, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma 2003;55:39–44. 22. Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma 2003;54:1127–30. 23. Sihler KC, Napolitano LM. Massive transfusion: new insights. Chest 2009;136:1654–67. 24. Bomken C, Mathai S, Biss T, Loughney A, Hanley J. Recombinant activated factor VII (rFVIIa) in the management of major obstetric haemorrhage: a case series and a proposed guideline for use. Obstetr Gynecol Int 2009; Article ID 364843. 25. Welsh A, McLintock C, Gatt S, Somerset D, Popham P, Ogle R. Guidelines for the use of recombinant activated factor VII in massive obstetric haemorrhage. Aust N Z J Obstet Gynaecol 2008;48:12–6.



0959-289X/$-see front matter c 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.ijoa.2011.09.009

Anesthetic management of vaginal delivery in a parturient with hemochromatosis induced end-organ failure A.L. Hoefnagel, R. Wissler Department of Anesthesiology, University of Rochester Medical Center, Rochester, NY, USA ABSTRACT The vast majority of females affected by hemochromatosis are asymptomatic during childbearing years. We were able to provide effective obstetric anesthesia care to a 35-year-old woman with severe hemochromatosis. She had systolic heart failure with a left ventricular ejection fraction of 15%, severe pulmonary hypertension, mitral insufficiency, a history of ventricular tachycardia, cirrhosis, obstructive sleep apnea, gestational diabetes, and severe scoliosis. A multidisciplinary approach was used to stabilize her heart failure and prepare her for childbirth. An arterial line and epidural analgesic were placed before induction of labor. Vaginal delivery was accomplished with passive decent of the fetus and forceps assistance. We discuss hemochromatosis and its implications for the parturient. c 2011 Elsevier Ltd. All rights reserved.



Keywords: Hemochromatosis; Pregnancy; Analgesia; Epidural

Accepted September 2011 Correspondence to: A.L. Hoefnagel, M.D., Department of Anesthesiology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 604, Rochester, NY 14642, USA. E-mail address: [email protected]

Introduction Hemochromatosis is an autosomal recessive genetic disorder affecting the ability of the body to metabolize