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Perioperative problems and treatment of a teenager with a juvenile angiofibroma refusing blood transfusion
International Journal of Pediatric Otorhinolaryngology 73 (2009) 689–692
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Perioperative problems and treatment of a teenager with a juvenile angiofibroma refusing blood transfusion Lechoslaw Pawel Chmielik a,*, Magdalena Frackiewicz a, Romuald Krajewski b, Bogumila Woloszczuk-Gebicka c, Mieczyslaw Chmielik a a b c
Department of Paediatric Otolaryngology, Medical University of Warsaw, Marszalkowska 24, Warsaw, Poland Head and Neck Cancer Department, Cancer-Center M. Skłodowska-Curie Memorial Institute Warsaw, Poland Department of Paediatric Anaesthesiology and Intensive care, Medical University of Warsaw, Poland
A R T I C L E I N F O
A B S T R A C T
Article history: Received 26 October 2008 Received in revised form 1 January 2009 Accepted 6 January 2009 Available online 20 February 2009
Objectives: Juvenile angiofibroma is a benign, non-encapsulated neoplasm, consisting of vascular and connective tissue. Its main feature is a local malignancy. In its clinical course it destroys adjoining structures, without metastasizing. It appears rarely, and is mainly found in boys at puberty. Among theories about the aetiology of juvenile angiofibroma, we must consider a haematoma-like lesion, an angioma with an extended fibrous component, or type of inflammatory allergic polyp. In the development of the lesion the participation of hormonal disorders on the pituitary gland-gonad axis is also suggested. According to the latest research, juvenile angiofibroma is regarded as a developmental defect, affecting the embryonic vascular network surrounding the sphenoid bone. Methods: If the patient or his/her parents refuse blood transfusion and use of blood products, it is necessary to apply modifications in the routine perioperative treatment. In the case of the patient refusing blood and blood products transfusion because of their beliefs, it is possible to get consent to use different, highly processed products like albumins or a cryoprecipitate, as well as applying some bloodsaving techniques. Conclusions:
Keywords: Juvenile angiofibroma Refusing blood transfusion Normovolaemic haemodilution
1. Removal of juvenile angiofibroma with minimal bleeding is possible. 2. Applying erythropoietin and iron preparations prior to surgery increases erythropoiesis and reduces the risks in transfusion. 3. Applying intraoperative normovolaemic haemodilution is a safe method and allows avoidance of transfusion of blood-derived products. ß 2009 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Juvenile angiofibroma is a benign, non-encapsulated neoplasm, consisting of vascular and connective tissue. Its main feature is a local malignancy. In its clinical course it destroys adjoining structures, without metastasizing. It appears rarely, and is mainly found in boys at puberty. Among theories about the aetiology of juvenile angiofibroma, we must consider a haematoma-like lesion, an angioma with an extended fibrous component, or type of inflammatory allergic polyp. In the development of the lesion the participation of
* Corresponding author. Tel.: +48 601217979. E-mail address: [email protected] (L.P. Chmielik). 0165-5876/$ – see front matter ß 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2009.01.013
hormonal disorders on the pituitary gland-gonad axis is also suggested [23]. According to the latest research, juvenile angiofibroma is regarded as a developmental defect, affecting the embryonic vascular network surrounding the sphenoid bone. The neoplasm grows in the vicinity of the sphenopalatine foramen [16,20] and extends in the direction of neighbouring structures: nasal cavities, the nasopharynx, the maxillary, sphenoid and ethmoid sinuses, the pterygopalatine fossa, the temporal fossa, or orbit, and can grow to the anterior and middle cranial fossas [7]. Characteristic clinical symptoms include progressive impairment of nasal patency (uni- or bilateral) and recurring epitaxis. With time, manifestations connected with proliferation of the tumour to adjoining structures may occur [3], e.g.: loss of smell, facial pain, headaches, protrusion of the orbit, and facial deformation.
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L.P. Chmielik et al. / International Journal of Pediatric Otorhinolaryngology 73 (2009) 689–692
There are several classifications of juvenile angiofibroma; the most frequently used are: Chandler’s classification, that of Fish, or the latest according to Radkowski [3,17,24]. Diagnosis of juvenile angiofibroma is based on anamnesis, ENT examination, endoscopy of the nasal cavities, radiological examinations (computed axial tomography, or magnetic resonance) and on arteriography. Treatment methods include surgery, radiotherapy and steroid therapy [7,20]. Surgical techniques include lateral rhinotomy, maxillotomy, a transpalatine approach, midface degloving [11], the Fish approach, and recently there has been an increase in the use of endoscopic methods [12,15,24]. Surgery may produce significant blood loss, in some cases exceeding the circulating blood volume, so therefore embolization of afferent vessels supplying the tumour, before the surgical procedure, is recommended [3,14,16]. If the patient or his/her parents refuse blood transfusion and use of blood products, it is necessary to apply modifications in the routine perioperative treatment. In the case of the patient refusing blood and blood products transfusion because of their beliefs, it is possible to get consent to use different, highly processed products like albumins or a cryoprecipitate, as well as applying some bloodsaving techniques. Both the surgical procedure and anaesthesia for a patient not giving his assent to blood transfusion need the most careful planning. The first step is to assess whether it is possible to proceed without a blood transfusion, which requires estimation of the tolerable blood loss (Table 1). The necessity for a blood transfusion is more probable when the concentration of haemoglobin before the operation is low, and hence it is reasonable to plan surgical treatment when the concentration of haemoglobin is optimal. Sideropenia is the most frequent cause of anaemia, so if there is enough time, treatment with iron preparations given orally or parenterally should be applied. Administration of erythropoietin in the preoperative period accelerates the production of erythrocytes in the bone marrow, and increases the concentration of haemoglobin and the haematocrit. More than 10 years ago, using erythropoietin in patients participating in the programme called ‘‘predonation’’ (for patients programme who give blood in the preoperative period), was accepted in the USA, Japan, Canada and many European countries [8]. Unfortunately, such procedures are very expensive.
right nasal cavity was shown. In radiological examinations (CT, NMR) an abnormal tissue mass, intensifying after use of a contrast medium, was revealed in the right nasal meatus, throat, subtemporal fossa and right maxillary sinus (Fig. 1). A preliminary diagnosis of juvenile angiofibroma was made and the boy was qualified for surgical treatment. The patient and his parents were informed that during the surgical procedure the blood loss could exceed the volume of circulating blood, and a blood transfusion night be needed. The patient and parents gave their consent to the operation, but did not consent to blood transfusion for religious reasons. The hospital filed for permission from the Family Court for Children and Juveniles, to use blood substitutes in case of an immediate threat to life resulting from bleeding that could not be stopped. The court decided ‘‘(. . .) to grant permission to use blood and blood platelets concentrate during the surgical procedure of tumour removal from the nasal area’’. The patient was given special treatment before the operation, which among others included administering erythropoietin (40,000 units), performing arteriography on the external carotid arteries and right internal carotid artery, with embolization of the artery supplying the lesion (right maxillary artery) and, after agreement with the anaesthetist, applying blood-sparing techniques. The preoperative blood count was as follows: Hb-15.3 g/dl, Htc-44.0%, platelets-380 1000 ml. After the induction of anaesthesia ‘‘acute’’ normovolaemic haemodilution was performed; 1393 ml of blood were drawn from the patient without disconnecting the blood transfusion set from the patient’s circulation, and the circulating blood volume was restored with HES130.000/0.4 solution. 2.1. Course of surgery A right-sided maxillotomy was performed, the whole lesion being removed in one piece from the nasopharynx, right maxillary sinus and pterygopalatine fossa. The result of intra-operative morphology was: Hb-10.7 g%, Ht-30.2% and RBC-3.7 106 mm3. Posterior packings and dressings were placed in the post-operative cavity. After all major bleeding stopped, autologous blood drawn before the operation was re-transfused. After a 3.5-month period, the patient came to the Clinic with impaired nasal patency on the right side, and recurrence of nasal
2. Case report A 16.5-year-old boy was admitted to the Department of Paediatric Otorhinolaryngology of Warsaw Medical University. In anamnesis the patient mentioned difficulties in breathing through his nose, progressing for the previous 3 months, and reoccurring epistaxis for the last 6 weeks. On admission, under medical examination, a blockage of the right nasal cavity and impaired patency of the left nasal cavity was found. Endoscopy of the nasal cavities was performed and a solid, greyish lesion in the Table 1 Calculation of the tolerable blood loss and the demand for blood. Tolerable blood loss = EBV (preoperative Hct lowest acceptable Hct)/ preoperative Hct. EBV, estimated blood volume. In children this is 70–75 ml kg1/m.c. Hct, haematocrit. Tolerated blood loss = the blood volume that the patient can lose before Hct decreases to the lowest acceptable value. The lowest acceptable haematocrit = minimum value of the haematocrit that should be safe for the patient; this value must be determined individually for every patient. For healthy children during anaesthesia, the lowest acceptable Htc is between 20 and 24% [1,2]. Expected demand for the transfusion = expected blood loss tolerable blood loss. One should look for information about the expected blood loss in retrospective data.
Fig. 1. In MRI an abnormal tissue mass.
L.P. Chmielik et al. / International Journal of Pediatric Otorhinolaryngology 73 (2009) 689–692
bleeding. In NMR a lesion was found in the sphenoid sinus. This was suspected to be a recurrence. Re-operation was performed, and no tumour was found in the area shown in NMR. However, the surgeons found pathologically changed, bleeding bone, which was removed. 3. Discussion Choosing an adequate surgical technique for the tumour was vital, and two approaches were considered: the Fish approach, which allows for better exposure of the blood vessels and better bleeding control, and maxillotomy which allows better access to the tumour and removal of it whole, but control of the supplying blood vessels may be more difficult. Since embolization of the supply vessels gave a good result, the final choice was maxillotomy. Data from literature suggests that blood loss during surgical removal of a juvenile fibroma can exceed the volume of the circulating blood. That was why we decided to put the boy under the custody of the court for the operation period. Blood is an extremely precious substance that saves lives, but it can also bring some potential threats (shock, infections, recurrence of neoplasm). Mainly because of these reasons, in the case of planned surgical treatment we should try to reduce the probability of allogenic blood transfusion. Personal religious beliefs of the patient and his family cannot be a criterion for refusal of surgical treatment. Careful planning of treatment is vital. It becomes necessary to establish which procedures the patient or his parents will consent to. In our case the patient and his parents gave their consent to intraoperative haemodilution and for the use of albumins and cryoprecipitate, but refused consent to and transfusion of packed RBCs and plasma. In the preoperative period, precautions against blood loss included: Calculation of the expected blood loss, establishing whether blood-saving techniques were likely to be needed, and calculation of the blood volume to be taken during intraoperative normovolaemic haemodilution (preoperative autologous blood donation was not accepted by the patient, and cell saving is not used in malignancy surgery). Support the erythropoiesis: 10 days before the operation the patient received 40,000 units (600 U/kg b.w.) of erythropoietin and iron preparation. Performing embolization of the tumour in order to reduce intraoperative bleeding. In planning intraoperative treatment we considered [5]: 1. Intraoperative normovolaemic haemodilution – harvesting blood after anaesthetic induction and replacing it with a plasma expander (colloidal or crystalloid), and then re-transfusing autologous blood after bleeding had stopped – or when the haematocrit decreased below the limit considered safe for the patient. 2. Inhibitors of fibrinolysis. 3. Supplementation of coagulation factors (recombined active VII factor). During the intraoperative normovolaemic haemodilution, the volume of blood to be harvested was calculated as follows: V ¼ EBV
Htc 0 Htc f Htc mean
V, blood volume to be collected; estimated blood volume (EBV) = 75 ml, body weight (kg) in children; Htc0, initial Htc; Htcf, final Htc after haemodilution; Htc mean, mean Ht.
691
The blood was drawn after inducing anaesthesia and retransfused after bleeding had stopped [5]. Blood is taken up into standard bags, the same as those used in a blood bank. It is necessary to work aseptically, because until re-transfusion the collected blood is kept in the operating theatre, at room temperature. For children, as for adults, blood or blood-derived products should not be used to maintain the circulating blood volume—this should be done with plasma expanders: crystalloids (3 ml per 1 ml blood loss), colloids (1 ml per 1 ml blood loss), or both. If volumes transfused are substantial, careful selection of the plasma expander becomes essential. ‘‘Normal’’ saline contains an excess of Cl (154 mmol l1), much higher than the physiological concentration. Rapid transfusion of 20 ml kg1 b.w. of normal saline or colloid solutions based on 0.9% NaCl can cause hyperchloraemic acidosis, which is not connected with greater mortality, like lactic acidosis, but is also not entirely benign [18,19]. Therefore, HES in a balanced electrolyte solution seems preferable for massive transfusion. Glucose should not be used as a plasma expander, since only 7% of the transfused volume stays in the vascular bed. Moreover, 5% glucose solution causes hyperglycaemia and hyponatraemia. Colloidal solutions are solutions of hydroxyethyl starch (HES) and gelatine solutions. The latter are quickly eliminated by the kidneys, and hence the time of the plasma expanding effect is not much longer than that of crystalloids. They can only be used for short-period volume replacement during haemodilution. Hydroxyethyl starches constitute the family of preparations that differ in physicochemical features that depend on the concentration (10% or 6%), molecular mass (450,000, 200,000 or 130,000 Da) and the degree of hydroxylation (0.7, 0.6, 0.5 or 0.4). Novel products, i.e.: HES 130,000/0.4 in balanced electrolyte solution (Na+ 137 mmol l1, K+ 4 mmol l1, Mg+ 2 mmol l1, Cl, osmolality 287 mosm l1), show minimal accumulation and seem to have only a minimal effect on coagulation [13]. This appears be the plasma expander of choice for massive transfusion. The maximum daily dose of 6% HES 130,000/0.4 is 50 ml kg1 (for adults; for children the maximum daily dose is not established). Intraoperative normovolaemic haemodilution is an effective blood-sparing technique in situations when intraoperative blood loss is considerable, initial value of haematocrit—high, and the lowest value of haematocrit during the operation—low [4]. Maintenance of correct tissue oxygenation during normovolaemic haemodilution is possible because of compensatory mechanisms. Reducing the blood viscosity triggered by a decline of the haematocrit causes a decrease in the systemic vascular resistance and an increase of the heart ejection fraction (EF) and cardiac output (CO). The second compensatory mechanism is increased oxygen extraction. The limits of safe haemodilution are unknown. Infrequent reports from medical literature reveal that children tolerate normovolaemic haemodilution well, but the number of cases described is small. A decrease of haematocrit to 24–20% in the intraoperative period is thought to be safe [1,2,25], but further decrease can cause serious neurological complications. The ‘‘critical’’ haemoglobin concentration is 3.5–4.7 g dl1 (Htc 12–14%). At this haemoglobin concentration the coronary vessels are already maximally dilated, and the coronary blood flow depends only on the cardiac output; so any decrease in the cardiac output caused by hypovolaemia, dysrhythmias or cardio-depressive effects of anaesthetics may lead to circulatory arrest. The second factor limiting haemodilution includes coagulopathy, caused by the decrease in plasmatic coagulation factors, low haematocrit, and also the unfavourable influence of some plasma expanders on the coagulation system. Antifibrinolytic drugs can be helpful, particularly in keeping the post-operative bleeding under control. Nowadays, to achieve this
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effect lysine analogues are used, but most of all epsilonaminocaproic acid, which has recently been gaining in popularity, considering its low cost and the lack of side effects, which are observed after aprotynin (already abandoned in many countries due to nephrotoxic properties). In cases of uncontrollable bleeding caused by multifactorial coagulopathy connected with the utilization of coagulation factors, haemodilution, or thrombocytopaenia, the activation of fibrinolysis, hypothermia and metabolic acidosis recombinant activated VII factor (rFVIIa) should be considered. However rFVIIa is registered only for patients suffering from haemophilia, but in the literature more and more reports of its effectiveness in controlling serious bleeding are appearing [9,10,21]. Such therapeutic proceedings require further controlled studies [22]. If all the methods mentioned above turn out to be ineffective, and the operated child is in danger of death from excessive blood loss, the use of blood products should be considered in spite of the disagreement of the patient and/or parents. In many cases the parents of operated children are ready to accept the necessity of such proceedings. If a consensus cannot be reached, the consent of the Protecting Court to implement life-saving procedures can be called on. When deciding to carry out life-saving procedures in spite of the patient’s/parent’s or statutory representative’s wishes, doctors should take into account that among operated adult patients (average age 57 17 years), whose haemoglobin concentration in the post-operative period lowered to 4.1–5.0 g dl1, the death rate was as high as 34.4%, while mortality in the group of patients undergoing similar procedures whose haemoglobin concentration fluctuated between 7.1 and 8.0 amounted to zero. The death risk in the perioperative period increases 2.5 times in relation to the decrease of haemoglobin concentration for every 1 g dl1 below 8,0 g dl1, which means that mortality at a haemoglobin concentration of 5–6 g dl1 increases drastically [6] 4. Conclusions 1. Removal of juvenile angiofibroma with minimal bleeding is possible. 2. Applying erythropoietin and iron preparations prior to surgery increases erythropoiesis and reduces the risks in transfusion. 3. Applying intraoperative normovolaemic haemodilution is a safe method and allows avoidance of transfusion of blood-derived products. References [1] S. Barcelona, A.A. Thompson, C.J. Cote, Intraoperative, pediatric blood transfusion therapy: a review of common issues. Part II: transfusion therapy, special considerations, and reduction of allogenic blood transfusions, Paediatr. Anaesth. 15 (2005) 815–830.
[2] S.L. Barcelona, A.A. Thompson, C.J. Cote´, Intraoperative pediatric blood transfusion therapy: a review of common issues. Part I: hematologic and physiologic differences from adults; metabolic and infectious risks, Paediatr. Anaesth. 15 (September (9)) (2005) 716–726. [3] S. Betlejewski, H. Mackiewicz-Nartowicz, A. Garstecka, Wło´kniak młodzien´czy Otolaryngol. 3 (1) (2004) 15–18. [4] G.L. Bryson, A. Laupacis, G.A. Wells, Does acute normovolemic hemodilution reduce perioperative allogeneic transfusion? A meta-analysis. The international study of perioperative transfusion, Anesth. Analg. 86 (January (1)) (1998) 9–15. [5] G.L. Bryson, A. Laupacis, G.A. Wells, Does acute normovolemic hemodilution reduce perioperative allogenic transfusion? A meta-analysis. The international study of perioperative transfusion, Anesth. Analg. 86 (1998) 9–15. [6] J.L. Carsons, H. Noveck, J.A. Berlin, et al., Mortality and morbidity in patients with very low postoperative Hb levels who decline blood transfusion, Transfusion 42 (2002) 812–818. [7] J.N. Fields, K.J. Halverson, V.R. Devineni, J.R. Simpson, C.A. Perez, Juvenile nasopharyngeal angiofibroma efficacy of radiation therapy, Radiology 176 (1) (1990) 263–265. [8] L.T. Goodnough, T.J. Monk, G.L. Andriole, Current concepts: erythropoietin therapy, N. Engl. J. Med. 336 (1997) 933–938. [9] G. Hammer, Use of recombinant activated factor VII in children (editorial), Paediatr. Anaesth. 17 (2007) 1123–1125. [10] G.B. Hammer, Williams GD use of recombinant activated factor VII in children, Paeditr. Anaesth. 17 (December (12)) (2007) 1123–1125. [11] D.J. Howard, V.J. Lund, The role of midfacial degloving in modern rhinological practice, J. Laryngol. Otol. 113 (1999) 885–887. [12] M. Jorissen, P. Eloy, P. Rombaux, C. Bachert, J. Daele, Endoscopic sinus surgery for juvenile nasopharyngeal angiofibroma, Acta Otorhinolaryngol. Belg. 54 (2000) 201–219. [13] O. Langeron, M. Doelberg, E.T. Ang, F. Bonnet, X. Capdevilla, P. Coriat, Voluven, a lower substituted novel hydroxyethyl starch (HES 130/0.4), causes fewer effects on coagulation in major orthopedic surgery than HES 200/0.5, Anesth. Analg. 92 (2001) 855–862. [14] G. Lloyd, D. Hovard, P. Phelps, A. Cheesman, Juvenile angiofibroma: the lessons of 20 years of modern imaging, J. Laryngol. Otol. 113 (2) (1999), 127–134{7}. [15] E. Mair, A. Battiata, J. Casler, Endoscopic laser-assisted excision of juvenile nasopharyngeal angiofibromas, Arch. Otolaryngol. Head Neck Surg. 129 (2003) 454–459. [16] H.B. Neel III, J.H. Whicker, K.D. Devine, H.L. Weiland, Juvenile angiofibroma: review of 120 cases, Am. J. Surg. 126 (1973) 547–556. [17] D. Radkowski, T. McGill, G.B. Healy, et al., Angiofibroma, changes in staging and treatment, Arch. Otolaryngol. Head Neck Surg. 122 (1996) 122–129. [18] F. Reid, D.N. Lobo, R.N. Williams, B.J. Rowlands, S.P. Allison, (Ab)normal saline and physiological Hartmannı´s solution: a randomized double-blind crossover study, Clin. Sci. (Lond.) 104 (2003) 25–26. [19] T.J. Reid, Hb-based oxygen carriers: are we there yet? Transfusion 43 (February (2)) (2003) 280–287. [20] G. Roger, P. Tran Ba Huy, P. Froehlich, T. Van Den Abbeele, J. Klossek, E. Serrano, E. Garabedian, P. Herman, Exclusively endoscopic removal of juvenile nasopharyngeal angiofibroma, Arch. Otolaryngol. Head Neck Surg. 128 (2002) 928–935. [21] S.J. Stanworth, C.J. Birchall, C.J. Doree, C. Hyde, Recombinant factor VIIa for the prevention and treatment of bleeding in patients without hemophilia, Cochrane Database Syst. Rev. 2 (2007), CD005011 17443565. [22] S.J. Stanworth, J. Birchall, C.J. Doree, C. Hyde, Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia, Cochrane Database Syst. Rev. 18 (April (2)) (2007), CD005011. [23] A. Szyman´ska, M. Szyman´ski, W. Krzyz˙anowski, W. Goła˛bek, M. Szczerbo-Trojanowska, Poste˛powanie diagnostyczne i leczenie w naczyniakowło´kniaku młodzien´czym, Magazyn Otorynolaryngologiczny-Otolaryngologia Dziecie˛ca, 2006 IX, tom X. [24] T. Tewfik, A. Tan, I. wsp, Juvenile nasopharyngeal angiofibroma, J. Otolaryngol. 28 (3) (1999) 145–151. [25] B. Wołoszczuk-Gebicka, How to limit allogenic blood transfusion in children, Paediatr. Anaesth. 15 (November) (2005) 913–924.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Perioperative problems and treatment of a teenager with a juvenile angiofibroma refusing blood transfusion Lechoslaw Pawel Chmielik a,*, Magdalena Frackiewicz a, Romuald Krajewski b, Bogumila Woloszczuk-Gebicka c, Mieczyslaw Chmielik a a b c
Department of Paediatric Otolaryngology, Medical University of Warsaw, Marszalkowska 24, Warsaw, Poland Head and Neck Cancer Department, Cancer-Center M. Skłodowska-Curie Memorial Institute Warsaw, Poland Department of Paediatric Anaesthesiology and Intensive care, Medical University of Warsaw, Poland
A R T I C L E I N F O
A B S T R A C T
Article history: Received 26 October 2008 Received in revised form 1 January 2009 Accepted 6 January 2009 Available online 20 February 2009
Objectives: Juvenile angiofibroma is a benign, non-encapsulated neoplasm, consisting of vascular and connective tissue. Its main feature is a local malignancy. In its clinical course it destroys adjoining structures, without metastasizing. It appears rarely, and is mainly found in boys at puberty. Among theories about the aetiology of juvenile angiofibroma, we must consider a haematoma-like lesion, an angioma with an extended fibrous component, or type of inflammatory allergic polyp. In the development of the lesion the participation of hormonal disorders on the pituitary gland-gonad axis is also suggested. According to the latest research, juvenile angiofibroma is regarded as a developmental defect, affecting the embryonic vascular network surrounding the sphenoid bone. Methods: If the patient or his/her parents refuse blood transfusion and use of blood products, it is necessary to apply modifications in the routine perioperative treatment. In the case of the patient refusing blood and blood products transfusion because of their beliefs, it is possible to get consent to use different, highly processed products like albumins or a cryoprecipitate, as well as applying some bloodsaving techniques. Conclusions:
Keywords: Juvenile angiofibroma Refusing blood transfusion Normovolaemic haemodilution
1. Removal of juvenile angiofibroma with minimal bleeding is possible. 2. Applying erythropoietin and iron preparations prior to surgery increases erythropoiesis and reduces the risks in transfusion. 3. Applying intraoperative normovolaemic haemodilution is a safe method and allows avoidance of transfusion of blood-derived products. ß 2009 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Juvenile angiofibroma is a benign, non-encapsulated neoplasm, consisting of vascular and connective tissue. Its main feature is a local malignancy. In its clinical course it destroys adjoining structures, without metastasizing. It appears rarely, and is mainly found in boys at puberty. Among theories about the aetiology of juvenile angiofibroma, we must consider a haematoma-like lesion, an angioma with an extended fibrous component, or type of inflammatory allergic polyp. In the development of the lesion the participation of
* Corresponding author. Tel.: +48 601217979. E-mail address: [email protected] (L.P. Chmielik). 0165-5876/$ – see front matter ß 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2009.01.013
hormonal disorders on the pituitary gland-gonad axis is also suggested [23]. According to the latest research, juvenile angiofibroma is regarded as a developmental defect, affecting the embryonic vascular network surrounding the sphenoid bone. The neoplasm grows in the vicinity of the sphenopalatine foramen [16,20] and extends in the direction of neighbouring structures: nasal cavities, the nasopharynx, the maxillary, sphenoid and ethmoid sinuses, the pterygopalatine fossa, the temporal fossa, or orbit, and can grow to the anterior and middle cranial fossas [7]. Characteristic clinical symptoms include progressive impairment of nasal patency (uni- or bilateral) and recurring epitaxis. With time, manifestations connected with proliferation of the tumour to adjoining structures may occur [3], e.g.: loss of smell, facial pain, headaches, protrusion of the orbit, and facial deformation.
690
L.P. Chmielik et al. / International Journal of Pediatric Otorhinolaryngology 73 (2009) 689–692
There are several classifications of juvenile angiofibroma; the most frequently used are: Chandler’s classification, that of Fish, or the latest according to Radkowski [3,17,24]. Diagnosis of juvenile angiofibroma is based on anamnesis, ENT examination, endoscopy of the nasal cavities, radiological examinations (computed axial tomography, or magnetic resonance) and on arteriography. Treatment methods include surgery, radiotherapy and steroid therapy [7,20]. Surgical techniques include lateral rhinotomy, maxillotomy, a transpalatine approach, midface degloving [11], the Fish approach, and recently there has been an increase in the use of endoscopic methods [12,15,24]. Surgery may produce significant blood loss, in some cases exceeding the circulating blood volume, so therefore embolization of afferent vessels supplying the tumour, before the surgical procedure, is recommended [3,14,16]. If the patient or his/her parents refuse blood transfusion and use of blood products, it is necessary to apply modifications in the routine perioperative treatment. In the case of the patient refusing blood and blood products transfusion because of their beliefs, it is possible to get consent to use different, highly processed products like albumins or a cryoprecipitate, as well as applying some bloodsaving techniques. Both the surgical procedure and anaesthesia for a patient not giving his assent to blood transfusion need the most careful planning. The first step is to assess whether it is possible to proceed without a blood transfusion, which requires estimation of the tolerable blood loss (Table 1). The necessity for a blood transfusion is more probable when the concentration of haemoglobin before the operation is low, and hence it is reasonable to plan surgical treatment when the concentration of haemoglobin is optimal. Sideropenia is the most frequent cause of anaemia, so if there is enough time, treatment with iron preparations given orally or parenterally should be applied. Administration of erythropoietin in the preoperative period accelerates the production of erythrocytes in the bone marrow, and increases the concentration of haemoglobin and the haematocrit. More than 10 years ago, using erythropoietin in patients participating in the programme called ‘‘predonation’’ (for patients programme who give blood in the preoperative period), was accepted in the USA, Japan, Canada and many European countries [8]. Unfortunately, such procedures are very expensive.
right nasal cavity was shown. In radiological examinations (CT, NMR) an abnormal tissue mass, intensifying after use of a contrast medium, was revealed in the right nasal meatus, throat, subtemporal fossa and right maxillary sinus (Fig. 1). A preliminary diagnosis of juvenile angiofibroma was made and the boy was qualified for surgical treatment. The patient and his parents were informed that during the surgical procedure the blood loss could exceed the volume of circulating blood, and a blood transfusion night be needed. The patient and parents gave their consent to the operation, but did not consent to blood transfusion for religious reasons. The hospital filed for permission from the Family Court for Children and Juveniles, to use blood substitutes in case of an immediate threat to life resulting from bleeding that could not be stopped. The court decided ‘‘(. . .) to grant permission to use blood and blood platelets concentrate during the surgical procedure of tumour removal from the nasal area’’. The patient was given special treatment before the operation, which among others included administering erythropoietin (40,000 units), performing arteriography on the external carotid arteries and right internal carotid artery, with embolization of the artery supplying the lesion (right maxillary artery) and, after agreement with the anaesthetist, applying blood-sparing techniques. The preoperative blood count was as follows: Hb-15.3 g/dl, Htc-44.0%, platelets-380 1000 ml. After the induction of anaesthesia ‘‘acute’’ normovolaemic haemodilution was performed; 1393 ml of blood were drawn from the patient without disconnecting the blood transfusion set from the patient’s circulation, and the circulating blood volume was restored with HES130.000/0.4 solution. 2.1. Course of surgery A right-sided maxillotomy was performed, the whole lesion being removed in one piece from the nasopharynx, right maxillary sinus and pterygopalatine fossa. The result of intra-operative morphology was: Hb-10.7 g%, Ht-30.2% and RBC-3.7 106 mm3. Posterior packings and dressings were placed in the post-operative cavity. After all major bleeding stopped, autologous blood drawn before the operation was re-transfused. After a 3.5-month period, the patient came to the Clinic with impaired nasal patency on the right side, and recurrence of nasal
2. Case report A 16.5-year-old boy was admitted to the Department of Paediatric Otorhinolaryngology of Warsaw Medical University. In anamnesis the patient mentioned difficulties in breathing through his nose, progressing for the previous 3 months, and reoccurring epistaxis for the last 6 weeks. On admission, under medical examination, a blockage of the right nasal cavity and impaired patency of the left nasal cavity was found. Endoscopy of the nasal cavities was performed and a solid, greyish lesion in the Table 1 Calculation of the tolerable blood loss and the demand for blood. Tolerable blood loss = EBV (preoperative Hct lowest acceptable Hct)/ preoperative Hct. EBV, estimated blood volume. In children this is 70–75 ml kg1/m.c. Hct, haematocrit. Tolerated blood loss = the blood volume that the patient can lose before Hct decreases to the lowest acceptable value. The lowest acceptable haematocrit = minimum value of the haematocrit that should be safe for the patient; this value must be determined individually for every patient. For healthy children during anaesthesia, the lowest acceptable Htc is between 20 and 24% [1,2]. Expected demand for the transfusion = expected blood loss tolerable blood loss. One should look for information about the expected blood loss in retrospective data.
Fig. 1. In MRI an abnormal tissue mass.
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bleeding. In NMR a lesion was found in the sphenoid sinus. This was suspected to be a recurrence. Re-operation was performed, and no tumour was found in the area shown in NMR. However, the surgeons found pathologically changed, bleeding bone, which was removed. 3. Discussion Choosing an adequate surgical technique for the tumour was vital, and two approaches were considered: the Fish approach, which allows for better exposure of the blood vessels and better bleeding control, and maxillotomy which allows better access to the tumour and removal of it whole, but control of the supplying blood vessels may be more difficult. Since embolization of the supply vessels gave a good result, the final choice was maxillotomy. Data from literature suggests that blood loss during surgical removal of a juvenile fibroma can exceed the volume of the circulating blood. That was why we decided to put the boy under the custody of the court for the operation period. Blood is an extremely precious substance that saves lives, but it can also bring some potential threats (shock, infections, recurrence of neoplasm). Mainly because of these reasons, in the case of planned surgical treatment we should try to reduce the probability of allogenic blood transfusion. Personal religious beliefs of the patient and his family cannot be a criterion for refusal of surgical treatment. Careful planning of treatment is vital. It becomes necessary to establish which procedures the patient or his parents will consent to. In our case the patient and his parents gave their consent to intraoperative haemodilution and for the use of albumins and cryoprecipitate, but refused consent to and transfusion of packed RBCs and plasma. In the preoperative period, precautions against blood loss included: Calculation of the expected blood loss, establishing whether blood-saving techniques were likely to be needed, and calculation of the blood volume to be taken during intraoperative normovolaemic haemodilution (preoperative autologous blood donation was not accepted by the patient, and cell saving is not used in malignancy surgery). Support the erythropoiesis: 10 days before the operation the patient received 40,000 units (600 U/kg b.w.) of erythropoietin and iron preparation. Performing embolization of the tumour in order to reduce intraoperative bleeding. In planning intraoperative treatment we considered [5]: 1. Intraoperative normovolaemic haemodilution – harvesting blood after anaesthetic induction and replacing it with a plasma expander (colloidal or crystalloid), and then re-transfusing autologous blood after bleeding had stopped – or when the haematocrit decreased below the limit considered safe for the patient. 2. Inhibitors of fibrinolysis. 3. Supplementation of coagulation factors (recombined active VII factor). During the intraoperative normovolaemic haemodilution, the volume of blood to be harvested was calculated as follows: V ¼ EBV
Htc 0 Htc f Htc mean
V, blood volume to be collected; estimated blood volume (EBV) = 75 ml, body weight (kg) in children; Htc0, initial Htc; Htcf, final Htc after haemodilution; Htc mean, mean Ht.
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The blood was drawn after inducing anaesthesia and retransfused after bleeding had stopped [5]. Blood is taken up into standard bags, the same as those used in a blood bank. It is necessary to work aseptically, because until re-transfusion the collected blood is kept in the operating theatre, at room temperature. For children, as for adults, blood or blood-derived products should not be used to maintain the circulating blood volume—this should be done with plasma expanders: crystalloids (3 ml per 1 ml blood loss), colloids (1 ml per 1 ml blood loss), or both. If volumes transfused are substantial, careful selection of the plasma expander becomes essential. ‘‘Normal’’ saline contains an excess of Cl (154 mmol l1), much higher than the physiological concentration. Rapid transfusion of 20 ml kg1 b.w. of normal saline or colloid solutions based on 0.9% NaCl can cause hyperchloraemic acidosis, which is not connected with greater mortality, like lactic acidosis, but is also not entirely benign [18,19]. Therefore, HES in a balanced electrolyte solution seems preferable for massive transfusion. Glucose should not be used as a plasma expander, since only 7% of the transfused volume stays in the vascular bed. Moreover, 5% glucose solution causes hyperglycaemia and hyponatraemia. Colloidal solutions are solutions of hydroxyethyl starch (HES) and gelatine solutions. The latter are quickly eliminated by the kidneys, and hence the time of the plasma expanding effect is not much longer than that of crystalloids. They can only be used for short-period volume replacement during haemodilution. Hydroxyethyl starches constitute the family of preparations that differ in physicochemical features that depend on the concentration (10% or 6%), molecular mass (450,000, 200,000 or 130,000 Da) and the degree of hydroxylation (0.7, 0.6, 0.5 or 0.4). Novel products, i.e.: HES 130,000/0.4 in balanced electrolyte solution (Na+ 137 mmol l1, K+ 4 mmol l1, Mg+ 2 mmol l1, Cl, osmolality 287 mosm l1), show minimal accumulation and seem to have only a minimal effect on coagulation [13]. This appears be the plasma expander of choice for massive transfusion. The maximum daily dose of 6% HES 130,000/0.4 is 50 ml kg1 (for adults; for children the maximum daily dose is not established). Intraoperative normovolaemic haemodilution is an effective blood-sparing technique in situations when intraoperative blood loss is considerable, initial value of haematocrit—high, and the lowest value of haematocrit during the operation—low [4]. Maintenance of correct tissue oxygenation during normovolaemic haemodilution is possible because of compensatory mechanisms. Reducing the blood viscosity triggered by a decline of the haematocrit causes a decrease in the systemic vascular resistance and an increase of the heart ejection fraction (EF) and cardiac output (CO). The second compensatory mechanism is increased oxygen extraction. The limits of safe haemodilution are unknown. Infrequent reports from medical literature reveal that children tolerate normovolaemic haemodilution well, but the number of cases described is small. A decrease of haematocrit to 24–20% in the intraoperative period is thought to be safe [1,2,25], but further decrease can cause serious neurological complications. The ‘‘critical’’ haemoglobin concentration is 3.5–4.7 g dl1 (Htc 12–14%). At this haemoglobin concentration the coronary vessels are already maximally dilated, and the coronary blood flow depends only on the cardiac output; so any decrease in the cardiac output caused by hypovolaemia, dysrhythmias or cardio-depressive effects of anaesthetics may lead to circulatory arrest. The second factor limiting haemodilution includes coagulopathy, caused by the decrease in plasmatic coagulation factors, low haematocrit, and also the unfavourable influence of some plasma expanders on the coagulation system. Antifibrinolytic drugs can be helpful, particularly in keeping the post-operative bleeding under control. Nowadays, to achieve this
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effect lysine analogues are used, but most of all epsilonaminocaproic acid, which has recently been gaining in popularity, considering its low cost and the lack of side effects, which are observed after aprotynin (already abandoned in many countries due to nephrotoxic properties). In cases of uncontrollable bleeding caused by multifactorial coagulopathy connected with the utilization of coagulation factors, haemodilution, or thrombocytopaenia, the activation of fibrinolysis, hypothermia and metabolic acidosis recombinant activated VII factor (rFVIIa) should be considered. However rFVIIa is registered only for patients suffering from haemophilia, but in the literature more and more reports of its effectiveness in controlling serious bleeding are appearing [9,10,21]. Such therapeutic proceedings require further controlled studies [22]. If all the methods mentioned above turn out to be ineffective, and the operated child is in danger of death from excessive blood loss, the use of blood products should be considered in spite of the disagreement of the patient and/or parents. In many cases the parents of operated children are ready to accept the necessity of such proceedings. If a consensus cannot be reached, the consent of the Protecting Court to implement life-saving procedures can be called on. When deciding to carry out life-saving procedures in spite of the patient’s/parent’s or statutory representative’s wishes, doctors should take into account that among operated adult patients (average age 57 17 years), whose haemoglobin concentration in the post-operative period lowered to 4.1–5.0 g dl1, the death rate was as high as 34.4%, while mortality in the group of patients undergoing similar procedures whose haemoglobin concentration fluctuated between 7.1 and 8.0 amounted to zero. The death risk in the perioperative period increases 2.5 times in relation to the decrease of haemoglobin concentration for every 1 g dl1 below 8,0 g dl1, which means that mortality at a haemoglobin concentration of 5–6 g dl1 increases drastically [6] 4. Conclusions 1. Removal of juvenile angiofibroma with minimal bleeding is possible. 2. Applying erythropoietin and iron preparations prior to surgery increases erythropoiesis and reduces the risks in transfusion. 3. Applying intraoperative normovolaemic haemodilution is a safe method and allows avoidance of transfusion of blood-derived products. References [1] S. Barcelona, A.A. Thompson, C.J. Cote, Intraoperative, pediatric blood transfusion therapy: a review of common issues. Part II: transfusion therapy, special considerations, and reduction of allogenic blood transfusions, Paediatr. Anaesth. 15 (2005) 815–830.
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