International Journal of Pediatric Otorhinolaryngology 79 (2015) 254–258
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Case Report
Non-fatal extensive cerebral venous thrombosis as a complication of adenotonsillectomy Ronak Rahmanian, Veronique Wan Fook Cheung, Neil K. Chadha * Division of Pediatric Otolaryngology-Head and Neck Surgery, B.C. Children’s Hospital, K2-184, 4480 Oak Street, Vancouver, BC V6H 3V4, Canada
A R T I C L E I N F O
A B S T R A C T
Article history: Received 1 August 2014 Received in revised form 9 November 2014 Accepted 14 November 2014 Available online 25 November 2014
Adenotonsillectomy, a common ambulatory surgical procedure performed in the pediatric population, may at times lead to serious postoperative complications. The case of a 10-year-old with extensive cerebral venous thrombosis (CVT) following routine adenotonsillectomy is presented and the likely risk factors are discussed. Recent literature regarding CVT in children will be reviewed. To our knowledge, there are no previous reports in the Otolaryngology literature of extensive CVT as a complication of adenotonsillectomy. This clinical entity is more common than previously thought. Awareness and a high index of suspicion and initiation of timely management can reduce the risk of potentially fatal outcomes. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Adenotonsillectomy Thrombosis Cerebral venous thrombosis Post-adenotonsillectomy complication Obstructive sleep apnea
1. Introduction Adenotonsillectomy is one of the most common ambulatory surgical procedures performed in the pediatric population [1]. Sleep disordered breathing, obstructive sleep apnea and recurrent throat infection are the most common indications, all of which can significantly impact a child’s quality of life [1]. Despite its routine nature, throat pain, postoperative nausea and vomiting, delayed feeding and postoperative hemorrhage are some of the more commonly encountered adverse outcomes [2–4]. However, there are rare but serious and possibly life threatening complications that may arise. Awareness of all potential complications and appropriate recognition by the responsible surgeon will help to ensure proper patient management and the avoidance of possibly disastrous patient outcomes. Following is a case report of a 10-year-old child that underwent routine uncomplicated adenotonsillectomy for obstructive sleep apnea, who presented on postoperative day 14 with worsening headache and persistent emesis and was found to have extensive cerebral venous thrombosis (CVT) on CT imaging. This is a very rare yet serious complication. This case is reviewed as well as the possible contributing risk factors resulting in this adverse outcome. An overview of the presentation, management and
* Corresponding author. Tel.: +1 604 875 3730. E-mail address: [email protected] (N.K. Chadha). http://dx.doi.org/10.1016/j.ijporl.2014.11.016 0165-5876/ß 2014 Elsevier Ireland Ltd. All rights reserved.
outcome of cerebral venous thrombosis in children as pertaining to this case will also be discussed. Appropriate informed consent was obtained from the patient and his parents prior to the report of this case. 2. Case report LB was a 10-year-old boy when he presented to the Pediatric Otolaryngology Clinic at BC Children’s Hospital with sleep disordered breathing with associated morning headaches and daytime sleepiness, nasal congestion, snoring and mouth breathing. He was obese, with a weight of 49.9 kg (98% percentile) and his blood pressure was in the upper limits of normal (110/80). Oropharyngeal examination showed bilateral grade 3 tonsillar hypertrophy. Fiberoptic nasal endoscopy revealed moderately enlarged adenoids. He was referred to Pediatric Respirology for a polysomnogram, which demonstrated severe obstructive sleep apnea with an Apnea Hypopnea index (AHI) of 92.5 with associated oxygen desaturations as low as 58%. Past medical history included birth by C-section secondary to failure to progress and possible chorioamnionitis. There were no complications from birth and he was discharged home without delay. He was otherwise healthy and had met all his ageappropriate developmental milestones. Family history was significant for thalassemia minor in his maternal uncle but there was no family history of deep venous thrombosis, pulmonary embolisms or autoimmune conditions. He had previously used fluticasone
R. Rahmanian et al. / International Journal of Pediatric Otorhinolaryngology 79 (2015) 254–258
nasal spray for more than a year without significant improvement in his chronic symptom of nasal obstruction and congestion. The patient underwent a routine adenotonsillectomy at the Children’s Hospital, with the use of bipolar cautery for the tonsils and monopolar suction cautery for the adenoids. Monopolar cautery was not used during tonsillectomy. Topical 0.5% bupivacaine on soaked patties was placed on the tonsil beds for 2 min at the end of the procedure. The child had a planned overnight stay in the Pediatric Intensive Care Unit for monitoring. Overnight postoperatively, he had no desaturations. He had an excellent appetite and minimal discomfort on postoperative day (POD) 1. He was found to have a low-grade fever and was discharged home on a ten-day course of amoxicillin and clavulanic acid. Following discharge however, his oral intake decreased and he developed intermittent frontal headaches with nausea and vomiting starting on POD 3. He presented to a local Community Emergency Department (ED) on POD 6 and again on POD 7 due to persistence of his symptoms as well as neck discomfort and was admitted for intravenous fluid hydration. He presented on POD 14 to BC Children’s Hospital with worsening headache radiating to his occiput and persistent emesis. He had no noted weakness, sensory loss, visual changes, ataxia, seizure episodes, or changes in his mental status. On admission, he was alert and oriented, and had an unremarkable cardiac, respiratory, abdominal and dermatological exam. Oropharyngeal examination revealed expected postoperative changes with small amounts of granulation tissue in the tonsillar fossae. No neck edema or tenderness was demonstrated. On neurological examination, he had normal gait, cranial nerve function, tone, power and reflexes in all four extremities and there was no sign of meningismus. Mild papilledema, left greater than right, was noted on ophthalmologic exam. His visual acuity was 20/ 20 bilaterally with normal color vision. A CT scan with contrast of the head and neck was performed which showed extensive cerebral venous sinus thrombosis involving the length of the sagittal sinus through the right transverse sinus, sigmoid sinus and jugular bulb down to the right internal jugular vein to the level of C3, approximately 4 cm below the skull base (see Figs. 1 and 2). Although the left jugular vein and sigmoid sinus were patent, thrombus was also seen in the left transverse sinus, straight sinus to the vein of Galen and in both internal cerebral veins. There was no evidence of focal cerebral edema or hemorrhage, and the third and lateral ventricles were of normal size, shape and position. There were no signs of thrombophlebitis.
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His blood work showed a white count of 16.9 (normal range (NR) 3.9–10.2), hemoglobin of 135 (NR 118–146), platelets of 440 (NR 180–440). PT was 11.8 (NR 9.6–12), INR 1.09 (NR 0.87–1.11), APTT 22.5 (NR 22.5–28.1), dilute Russell’s viper venom time 1.03 (NR 0.76–1.15) and fibrinogen level 4.06 (N 1.68–4.4). His anticardiolipin antibody test was negative, and his antithrombin III and homocysteine levels were normal. Protein C activity was slightly elevated at 1.4 but was reported as not clinically significant by hematopathology. Protein S activity level was normal and testing for Factor V leiden and prothrombin (Factor II) mutations were negative. A blood film showed non-specific poikilocytosis and microcytic anemia in favor of iron deficiency. The Pediatric Neurology and Pediatric Hematology services were consulted. A lumbar puncture was performed which revealed increased intracranial pressures (opening pressure of 42 cm H2O). The CSF gram stain and culture were negative. The patient was started on prophylactic anti-seizure medication (levetiracetam 500 mg p.o. BID). He was started on acetazolamide 325 mg p.o. TID for elevated intracranial pressure. Enoxaparin (Low Molecular Weight Heparin) was initiated for his extensive cerebral venous thrombosis, which was titrated to a therapeutic goal (anti-Xa level of 0.5–1). He was discharged home on POD 19 as he had improved symptomatically and was able to tolerate oral hydration with a plan to continue anticoagulation for a 3month duration. Follow-up was arranged with the Neurology and Otolaryngology team at BC Children’s Hospital for reassessment and re-imaging to determine whether an additional 3 months of therapy would be required. On follow-up he was noted to have decreased headache frequency and severity. He had no associated nausea or emesis since discharge and his papilledema had improved. His repeat imaging at 3 months revealed resolution of his cerebral venous thrombosis (see Figs. 3 and 4) and his repeat polysomnography demonstrated a dramatic improvement in his sleep apnea, with an AHI of 7.4 compared to his pre-operative AHI of 92.5. 3. Discussion Cerebral venous thrombosis is a serious yet very rare complication following adenotonsillectomy. There are only a few case reports in the literature that have reported on this complication, with the most recent being a case of superior sagittal thrombosis and cortical infarction reported by Reilly et al. in 2006, and a case of jugular thrombosis post tonsillectomy
Figs. 1 and 2. CT scan at the time of presentation. CT scan of the head and neck with contrast (coronal and sagittal views) demonstrating extensive cerebral venous sinus thrombosis involving the sagittal sinus, the right transverse sinus and the straight sinus (block arrows) with a patent left transverse sinus (dotted arrow).
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Figs. 3 and 4. CT scan 3 months following initial presentation. CT scan of the head and neck with contrast (coronal and sagittal views) demonstrating resolution of the cerebral venous sinus thrombosis (block arrows) following treatment.
reported by Nix in 2001 [5,6]. None of these previous reports, however, were as extensive as the thrombosis in the present case, which involved the right sagittal sinus, transverse sinus, sigmoid sinus, jugular bulb and internal jugular vein as well as the left transverse sinus, straight sinus, vein of Galen and both internal cerebral veins. The overall incidence of cerebral venous sinus thrombosis has been reported to be at least 0.67 per 100 000 children per year [7]. Previous studies have shown up to 16% mortality and an approximately 22% serious long-term neurologic morbidity associated with this diagnosis [8]. Diagnosis, however, is difficult and often missed as the presenting symptoms and signs are non-specific and the treating physician is frequently unaware of this clinical entity as a possible complication. Therefore, a high index of suspicion is required. Cerebral venous thrombosis is typically multifactorial and there are a wide variety of underlying disorders and risk factors including infection, dehydration, recent surgical procedure, renal failure, trauma, cancer and hematological disorders which can contribute to its development [7,8]. Ultimately, the potential contributing factors in thrombus formation can be described using Virchow’s triad of hypercoagulability, hemodynamic changes/stasis and endothelial injury/dysfunction. 3.1. Risk factors Hypercoagulability and prothrombotic disorders were found in 33–62% of cases in recent reports of pediatric CVT, which included acquired prothrombotic states, such as acute protein C and S and antithrombin deficiency secondary to infection, surgery, trauma, malignancy or renal disease [7]. Recent studies have shown septic thrombosis to be responsible for a substantial proportion of thrombosis in older children with a reported three quarters of the CVT cases having an infectious trigger [7–10]. Although, in the case of our patient, hematologic investigations did not identify any inherited hypercoagulable disorders, his recent adenotonsillectomy as well as possible early post-operative infection may have contributed to the development of his CVT. It is important to point out however that his POD 1 fever was most likely due to postoperative atelectasis and transient bacteremia; and despite the low possibility of infection, the patient was treated with a 10-day course of appropriate antibiotics. In addition, there were no obvious signs of infection based on the history and clinical examination upon presentation.
Microcytosis with or without frank anemia suggestive of iron deficiency and at times in association with thrombocytosis in previously well children has been identified as yet another possible trigger [7]. A prospective study performed by Stolz and colleagues in 2007 demonstrated a significant and independent association between severe anemia (arbitrarily defined by the authors as Hgb < 90 g/l) and CVT [11]. Blood work and blood film investigations of our patient did not reveal evidence of severe anemia, however a platelet count of 440 (on the higher end of the normal range) as well as poikilocytosis and microcytic anemia did favor possible iron deficiency as a potential contributor to his CVT. The diagnosis of anemia may however have been obscured in our patient by relative hemoconcentration secondary to significant dehydration and a falsely elevated ferritin in the acute setting [12]. Dehydration and the resulting alterations in cerebral hemodynamics are an additional important treatable risk factor for pediatric CVT [6–10,12]. LB’s decrease in oral intake, as well as his recurrent episodes of emesis likely resulted in significant dehydration. This was suspected to be a major contributing factor to this patient’s extensive cerebral venous sinus thrombosis. Obstructive sleep-disordered breathing and obesity are two clinical conditions that can often co-exist. Obstructive sleep apnea (OSA), a more severe form of sleep-disordered breathing can affect up to 10% of the pediatric population, with adenotonsillar hypertrophy being the most common etiology [13]. OSA in children can lead to behavioral problems, systemic and pulmonary hypertension and other serious morbidities [13]. An examination of the relationship between OSA and in vitro hypercoagulability performed by Guardiola et al. in 2001 showed an association between OSA and global hypercoagulability [14]. Several previous studies also observed increased platelet activation and aggregation as well as increases in plasma fibrinogen concentration and whole blood viscosity in OSA patients [15,16]. A review of the literature by Liak and Fitzpatrick in 2011 found considerable data supporting an association between OSA and a procoagulant state, however the relationship between OSA and individual clotting factors is yet to be determined [17]. In addition, studies in the adult population have found obesity to be associated with impaired fibrinolysis due to elevated levels of plasminogen activator inhibitor, and demonstrated obesity as a risk factor for deep venous thrombosis [18,19]. Thus, LB’s weight of 49.9 kg (98% percentile) at the age of 10 and his severe obstructive sleep apnea as per his polysomnography, were comorbid conditions that were likely contributing etiologies for his CVT.
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The optimal technique in performing a tonsillectomy has been the center of debate with no one procedure having gained universal acceptance. Our patient underwent bipolar tonsillectomy, similar to the CVT case described by Nix in 2001 [6]. The method of tonsillectomy used by Reilly et al. was not reported [5]. Bipolar cautery is thought to cause minimal thermal damage to the surrounding tissue in comparison to monopolar cuatery/ hot knife, thereby reducing the potential risk of damage to the nearby vessels and the possibility of hypercoagulability. A previous study reported earlier return to normal activity and fewer total doses of pain medication following tonsillectomy with bipolar dissection, in comparison to hot or cold knife cautery [20]. This in theory should allow for improved postoperative hydration, therefore reducing the risk for further complications. In our case however, LB also underwent an adenoidectomy, performed by suction monopolar cautery, which could have lead to surrounding tissue and vascular endothelial thermal injury resulting in a possible hypercoagulable state. 3.2. Clinical manifestations and diagnosis The most common but least specific symptom of CVT found to be present in more than 90% of patients is severe headache which can be one of acute onset or gradually progressive [7–10,12]. CVT can present with a wide spectrum of signs and symptoms and the clinical presentation is affected by the age of the patient, time between onset and presentation, location of CVT and the presence of parenchymal lesions [10,21]. Neurologic signs such as seizures, focal neurological deficits, and loss of consciousness develop in approximately half of the affected patients, with unilateral hemispheric symptoms such as hemiparesis or aphasia being rare occurrences [10]. The key to diagnosis is a high index of suspicion, leading to early imaging and prompt management. Recommendations in the Guidelines on the Investigation, Management and Prevention of Venous Thrombosis in Children published in the British Journal of Hematology in 2011, suggested a prompt MRI including T2 imaging and MRV for diagnosis of both intraparenchymal hemorrhage and sinus thrombosis in children suspected of having CVT [22]. A pre- and post-contrast CT scan with CT venography should be performed as a first line investigation in cases where urgent MRI is unavailable [22]. The imaging should include the petrous temporal bones and air filled sinuses to assess for sinusitis and mastoiditis as potential underlying etiologies [22]. 3.3. Prognosis, recurrence and management Acute cerebral venous thrombosis has been reported to be associated with a 15% overall death rate [21]. However, the majority (90%) of children with CVT survive the initial illness [21]. Seizure at onset, CNS infection, intracranial hemorrhage or infarcts and mental status disorder are some of the long-term predictors of poor prognosis [7–10,12,21]. A European multicenter cohort study performed in 2007, found the overall yearly rate of a second venous thrombosis event in pediatric patients with CVT to be 22.2 per 1000 person-years within a median period of 6 months following the initial CVT [23]. Onset of CVT after age 2 years, failure to recanalize and presence of a factor II mutation were identified as risk factors for recurrent venous thrombosis [23]. Therefore, long-term follow up of affected children is paramount as patients may be at risk of recurrence and often the onset of signs of neurologic injury may be delayed in the pediatric population. Treatment of CVT involves general supportive care such as correction of dehydration and hypovolemia, administration of antibiotic therapy along with source control in the setting
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of infection, management of seizures with anticonvulsants and measures aimed at decreasing intracranial pressure [7–10,12]. According to the recent guidelines published for the treatment of CVT, administration of anticoagulant therapy with the aims of spontaneous thrombus resolution, avoidance of thrombus extension and prevention of pulmonary embolism is an integral part of the therapeutic measure [22]. Based on current evidence, patients with CVT without contraindications for anticoagulation therapy should be treated either with body weight-adjusted subcutaneous LMWH or dose-adjusted intravenous heparin with an at least doubled partial thromboplastin time. Concomitant intracranial hemorrhage related to CVT is not a contraindication for heparin therapy [12,22–24]. There are insufficient data regarding the optimal duration of oral anticoagulant therapy. Oral anticoagulants may be administered for 3 months if the CVT was secondary to a transient risk factor and for 6–12 months in patients with idiopathic CVT and in those with ‘mild’ hereditary thrombophilia. Indefinite anticoagulation should be considered in patients with two or more episodes of CVT or those with ‘severe’ hereditary thrombophilia [21,25]. There is insufficient evidence supporting the use of either systemic or local thrombolysis in patients with CVT, and it may be considered in select cases that deteriorate despite adequate anticoagulation in the absence of intracranial hemorrhage [21,22,25]. Follow up neuroimaging with MRI or CT venography is recommended to be undertaken in the acute phase and during the first year, with some centers performing repeat imaging at 3, 6 and 12 months after diagnosis to assess for evidence of extension, persistence or recanalization [12,22]. 4. Conclusion There is limited information in the Otolaryngology literature about cerebral venous thrombosis, especially as a complication of adenotonsillectomy. This clinical entity is associated with infections of the head and neck, and is likely more common than previously thought. Awareness by the Otolaryngologist and initiation of timely management of preventable risk factors such as severe dehydration or post-operative infection can reduce the risk of this potentially fatal outcome and possible future disability in the patient population. Conflict of interest The authors have no conflicts of interest to declare. References [1] R.F. Baugh, S.M. Archer, R.B. Mitchell, R.M. Rosenfeld, F. Amin, J.J. Burns, et al., Clinical practice guideline: tonsillectomy in children, American Academy of Otolaryngology – Head and Neck Surgery Foundation, Otolaryngol. Head Neck Surg. 144 (1 Suppl.) (2011) S1–S30. [2] D.A. Randall, M.E. Hoffer, Complications of tonsillectomy and adenoidectomy, Otolaryngol. Head Neck Surg. 118 (1998) 61–68. [3] L.B. Johnson, R.G. Elluru, C.M. Myer, Complications of adenotonsillectomy, Laryngoscope 112 (2002) 35–36. [4] R. Subramanyam, A. Varughese, J.P. Willging, S. Sadhasivam, Future of pediatric tonsillectomy and perioperative outcomes, Int. J. Pediatr. Otorhinolaryngol. 77 (2) (2013) 194–199. [5] M.J. Reilly, G. Milmoe, M. Pena, Three extraordinary complications of adenotonsillectomy, Int. J. Pediatr. Otorhinolaryngol. 70 (5) (2006) 941–946. [6] P.A. Nix, Jugular thrombosis following tonsillectomy, J. Laryngol. Otol. 115 (3) (2001) 238–239. [7] G. Sebire, B. Tabarki, D.E. Saunders, I. Leroy, R. Liesner, C. Saint-Martin, et al., Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome, Brain 128 (2005) 477–489. [8] K.S. Carvalho, J.B. Bodensteiner, P.J. Connolly, B.P. Garg, Cerebral venous thrombosis in children, J. Child. Neurol. 16 (8) (2001) 574–580. [9] M.G. Cousser, J.M. Ferro, Cerebral venous thrombosis: an update, Lancet Neurol. 6 (2007) 162–170. [10] J. Stam, Thrombosis of the cerebral veins and sinuses, N. Engl. J. Med. 352 (17) (2005) 1791–1798.
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[11] E. Stolz, J.M. Valdueza, M. Grebe, F. Schlachetzki, E. Schmitt, K. Madlener, et al., Anemia as a risk factor for cerebral venous thrombosis? An old hypothesis revisited, J. Neurol. 254 (2007) 729–734. [12] N. Dlamini, L. Billinghurst, F.J. Kirkham, Cerebral venous sinus (sinovenous) thrombosis in children, Neurosurg. Clin. N. Am. 21 (2010) 511–527. [13] M. Benninger, D. Walner, Obstructive sleep-disordered breathing in children, Clin. Cornerstone 9 (1 Suppl.) (2007) S6–S12. [14] J.J. Guardiola, P.J. Matheson, L.C. Clavijo, M.A. Wilson, E.C. Fletcher, Hypercoagulability in patients with obstructive sleep apnea, Sleep Med. 2 (2001) 517– 523. [15] G. Bokinsky, M. Miller, K. Ault, P. Husband, J. Mitchell, Spontaneous platelet activation and aggregation during OSA and its response to therapy with N-CPAP, Chest 108 (1995) 625–630. [16] C. Rangemark, J.A. Hedner, J.T. Carlson, G. Gleerup, K. Winther, Platelet function and fibrinolytic activity in hypertensive and normotensive sleep apnea patients, Sleep 18 (1995) 188–194. [17] C. Liak, M. Fitzpatrick, Coagulability in obstructive sleep apnea, Can. Respir. J. 18 (6) (2011) 338–348. [18] J.B. McGill, D.J. Schneider, C.L. Arfken, C.L. Lucore, B.E. Sobel, Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients, Diabetes 43 (1995) 104–109.
[19] P.D. Stein, A. Beernath, R.E. Olsen, Obesity as a risk factor in venous thromboembolism, Am. J. Med. 118 (9) (2005) 978–980. [20] M.P. Pizzuto, L. Brodsky, L. Duffy, J. Gendler, E. Nauenberg, A comparison of microbipolar cautery dissection to hot knife and cold knife cautery tonsillectomy, Int. J. Pediatr. Otorhinolaryngol. 52 (3) (2000) 239–246. [21] M.G. Bousser, J.M. Ferro, Cerebral venous thrombosis: an update, Lancet Neurol. 6 (2007) 162–170. [22] E. Chalmers, V. Ganesen, R. Liesner, S. Maroo, T. Nokes, D. Saunders, et al., Guideline on the investigation, management and prevention of venous thrombosis in children, Br. J. Haematol. 154 (2) (2011) 196–207. [23] G. Kent, F. Kirkham, T. Niederstadt, A. Heineche, D. Saunders, M. Stoll, et al., Risk factors for recurrent venous thromboembolism in the European collaborative paediatric database on cerebral venous thrombosis: a multicenter cohort study, Lancet Neurol. 6 (7) (2007) 595–603. [24] P. Monagle, A. Chan, P. Massicotte, E. Chalmers, A.D. Michelson, Antithrombotic therapy in children: the seventh ACCP conference on antithrombotic and thrombolytic therapy, Chest 126 (3 Suppl.) (2004) S645–S687. [25] K. Einhaupl, J. Stam, M.G. Bousser, S.F. De Bruijn, J.M. Ferro, I. Martinelli, et al., EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients, Eur. J. Neurol. 17 (10) (2012) 1229–1235.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Case Report
Non-fatal extensive cerebral venous thrombosis as a complication of adenotonsillectomy Ronak Rahmanian, Veronique Wan Fook Cheung, Neil K. Chadha * Division of Pediatric Otolaryngology-Head and Neck Surgery, B.C. Children’s Hospital, K2-184, 4480 Oak Street, Vancouver, BC V6H 3V4, Canada
A R T I C L E I N F O
A B S T R A C T
Article history: Received 1 August 2014 Received in revised form 9 November 2014 Accepted 14 November 2014 Available online 25 November 2014
Adenotonsillectomy, a common ambulatory surgical procedure performed in the pediatric population, may at times lead to serious postoperative complications. The case of a 10-year-old with extensive cerebral venous thrombosis (CVT) following routine adenotonsillectomy is presented and the likely risk factors are discussed. Recent literature regarding CVT in children will be reviewed. To our knowledge, there are no previous reports in the Otolaryngology literature of extensive CVT as a complication of adenotonsillectomy. This clinical entity is more common than previously thought. Awareness and a high index of suspicion and initiation of timely management can reduce the risk of potentially fatal outcomes. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Adenotonsillectomy Thrombosis Cerebral venous thrombosis Post-adenotonsillectomy complication Obstructive sleep apnea
1. Introduction Adenotonsillectomy is one of the most common ambulatory surgical procedures performed in the pediatric population [1]. Sleep disordered breathing, obstructive sleep apnea and recurrent throat infection are the most common indications, all of which can significantly impact a child’s quality of life [1]. Despite its routine nature, throat pain, postoperative nausea and vomiting, delayed feeding and postoperative hemorrhage are some of the more commonly encountered adverse outcomes [2–4]. However, there are rare but serious and possibly life threatening complications that may arise. Awareness of all potential complications and appropriate recognition by the responsible surgeon will help to ensure proper patient management and the avoidance of possibly disastrous patient outcomes. Following is a case report of a 10-year-old child that underwent routine uncomplicated adenotonsillectomy for obstructive sleep apnea, who presented on postoperative day 14 with worsening headache and persistent emesis and was found to have extensive cerebral venous thrombosis (CVT) on CT imaging. This is a very rare yet serious complication. This case is reviewed as well as the possible contributing risk factors resulting in this adverse outcome. An overview of the presentation, management and
* Corresponding author. Tel.: +1 604 875 3730. E-mail address: [email protected] (N.K. Chadha). http://dx.doi.org/10.1016/j.ijporl.2014.11.016 0165-5876/ß 2014 Elsevier Ireland Ltd. All rights reserved.
outcome of cerebral venous thrombosis in children as pertaining to this case will also be discussed. Appropriate informed consent was obtained from the patient and his parents prior to the report of this case. 2. Case report LB was a 10-year-old boy when he presented to the Pediatric Otolaryngology Clinic at BC Children’s Hospital with sleep disordered breathing with associated morning headaches and daytime sleepiness, nasal congestion, snoring and mouth breathing. He was obese, with a weight of 49.9 kg (98% percentile) and his blood pressure was in the upper limits of normal (110/80). Oropharyngeal examination showed bilateral grade 3 tonsillar hypertrophy. Fiberoptic nasal endoscopy revealed moderately enlarged adenoids. He was referred to Pediatric Respirology for a polysomnogram, which demonstrated severe obstructive sleep apnea with an Apnea Hypopnea index (AHI) of 92.5 with associated oxygen desaturations as low as 58%. Past medical history included birth by C-section secondary to failure to progress and possible chorioamnionitis. There were no complications from birth and he was discharged home without delay. He was otherwise healthy and had met all his ageappropriate developmental milestones. Family history was significant for thalassemia minor in his maternal uncle but there was no family history of deep venous thrombosis, pulmonary embolisms or autoimmune conditions. He had previously used fluticasone
R. Rahmanian et al. / International Journal of Pediatric Otorhinolaryngology 79 (2015) 254–258
nasal spray for more than a year without significant improvement in his chronic symptom of nasal obstruction and congestion. The patient underwent a routine adenotonsillectomy at the Children’s Hospital, with the use of bipolar cautery for the tonsils and monopolar suction cautery for the adenoids. Monopolar cautery was not used during tonsillectomy. Topical 0.5% bupivacaine on soaked patties was placed on the tonsil beds for 2 min at the end of the procedure. The child had a planned overnight stay in the Pediatric Intensive Care Unit for monitoring. Overnight postoperatively, he had no desaturations. He had an excellent appetite and minimal discomfort on postoperative day (POD) 1. He was found to have a low-grade fever and was discharged home on a ten-day course of amoxicillin and clavulanic acid. Following discharge however, his oral intake decreased and he developed intermittent frontal headaches with nausea and vomiting starting on POD 3. He presented to a local Community Emergency Department (ED) on POD 6 and again on POD 7 due to persistence of his symptoms as well as neck discomfort and was admitted for intravenous fluid hydration. He presented on POD 14 to BC Children’s Hospital with worsening headache radiating to his occiput and persistent emesis. He had no noted weakness, sensory loss, visual changes, ataxia, seizure episodes, or changes in his mental status. On admission, he was alert and oriented, and had an unremarkable cardiac, respiratory, abdominal and dermatological exam. Oropharyngeal examination revealed expected postoperative changes with small amounts of granulation tissue in the tonsillar fossae. No neck edema or tenderness was demonstrated. On neurological examination, he had normal gait, cranial nerve function, tone, power and reflexes in all four extremities and there was no sign of meningismus. Mild papilledema, left greater than right, was noted on ophthalmologic exam. His visual acuity was 20/ 20 bilaterally with normal color vision. A CT scan with contrast of the head and neck was performed which showed extensive cerebral venous sinus thrombosis involving the length of the sagittal sinus through the right transverse sinus, sigmoid sinus and jugular bulb down to the right internal jugular vein to the level of C3, approximately 4 cm below the skull base (see Figs. 1 and 2). Although the left jugular vein and sigmoid sinus were patent, thrombus was also seen in the left transverse sinus, straight sinus to the vein of Galen and in both internal cerebral veins. There was no evidence of focal cerebral edema or hemorrhage, and the third and lateral ventricles were of normal size, shape and position. There were no signs of thrombophlebitis.
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His blood work showed a white count of 16.9 (normal range (NR) 3.9–10.2), hemoglobin of 135 (NR 118–146), platelets of 440 (NR 180–440). PT was 11.8 (NR 9.6–12), INR 1.09 (NR 0.87–1.11), APTT 22.5 (NR 22.5–28.1), dilute Russell’s viper venom time 1.03 (NR 0.76–1.15) and fibrinogen level 4.06 (N 1.68–4.4). His anticardiolipin antibody test was negative, and his antithrombin III and homocysteine levels were normal. Protein C activity was slightly elevated at 1.4 but was reported as not clinically significant by hematopathology. Protein S activity level was normal and testing for Factor V leiden and prothrombin (Factor II) mutations were negative. A blood film showed non-specific poikilocytosis and microcytic anemia in favor of iron deficiency. The Pediatric Neurology and Pediatric Hematology services were consulted. A lumbar puncture was performed which revealed increased intracranial pressures (opening pressure of 42 cm H2O). The CSF gram stain and culture were negative. The patient was started on prophylactic anti-seizure medication (levetiracetam 500 mg p.o. BID). He was started on acetazolamide 325 mg p.o. TID for elevated intracranial pressure. Enoxaparin (Low Molecular Weight Heparin) was initiated for his extensive cerebral venous thrombosis, which was titrated to a therapeutic goal (anti-Xa level of 0.5–1). He was discharged home on POD 19 as he had improved symptomatically and was able to tolerate oral hydration with a plan to continue anticoagulation for a 3month duration. Follow-up was arranged with the Neurology and Otolaryngology team at BC Children’s Hospital for reassessment and re-imaging to determine whether an additional 3 months of therapy would be required. On follow-up he was noted to have decreased headache frequency and severity. He had no associated nausea or emesis since discharge and his papilledema had improved. His repeat imaging at 3 months revealed resolution of his cerebral venous thrombosis (see Figs. 3 and 4) and his repeat polysomnography demonstrated a dramatic improvement in his sleep apnea, with an AHI of 7.4 compared to his pre-operative AHI of 92.5. 3. Discussion Cerebral venous thrombosis is a serious yet very rare complication following adenotonsillectomy. There are only a few case reports in the literature that have reported on this complication, with the most recent being a case of superior sagittal thrombosis and cortical infarction reported by Reilly et al. in 2006, and a case of jugular thrombosis post tonsillectomy
Figs. 1 and 2. CT scan at the time of presentation. CT scan of the head and neck with contrast (coronal and sagittal views) demonstrating extensive cerebral venous sinus thrombosis involving the sagittal sinus, the right transverse sinus and the straight sinus (block arrows) with a patent left transverse sinus (dotted arrow).
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Figs. 3 and 4. CT scan 3 months following initial presentation. CT scan of the head and neck with contrast (coronal and sagittal views) demonstrating resolution of the cerebral venous sinus thrombosis (block arrows) following treatment.
reported by Nix in 2001 [5,6]. None of these previous reports, however, were as extensive as the thrombosis in the present case, which involved the right sagittal sinus, transverse sinus, sigmoid sinus, jugular bulb and internal jugular vein as well as the left transverse sinus, straight sinus, vein of Galen and both internal cerebral veins. The overall incidence of cerebral venous sinus thrombosis has been reported to be at least 0.67 per 100 000 children per year [7]. Previous studies have shown up to 16% mortality and an approximately 22% serious long-term neurologic morbidity associated with this diagnosis [8]. Diagnosis, however, is difficult and often missed as the presenting symptoms and signs are non-specific and the treating physician is frequently unaware of this clinical entity as a possible complication. Therefore, a high index of suspicion is required. Cerebral venous thrombosis is typically multifactorial and there are a wide variety of underlying disorders and risk factors including infection, dehydration, recent surgical procedure, renal failure, trauma, cancer and hematological disorders which can contribute to its development [7,8]. Ultimately, the potential contributing factors in thrombus formation can be described using Virchow’s triad of hypercoagulability, hemodynamic changes/stasis and endothelial injury/dysfunction. 3.1. Risk factors Hypercoagulability and prothrombotic disorders were found in 33–62% of cases in recent reports of pediatric CVT, which included acquired prothrombotic states, such as acute protein C and S and antithrombin deficiency secondary to infection, surgery, trauma, malignancy or renal disease [7]. Recent studies have shown septic thrombosis to be responsible for a substantial proportion of thrombosis in older children with a reported three quarters of the CVT cases having an infectious trigger [7–10]. Although, in the case of our patient, hematologic investigations did not identify any inherited hypercoagulable disorders, his recent adenotonsillectomy as well as possible early post-operative infection may have contributed to the development of his CVT. It is important to point out however that his POD 1 fever was most likely due to postoperative atelectasis and transient bacteremia; and despite the low possibility of infection, the patient was treated with a 10-day course of appropriate antibiotics. In addition, there were no obvious signs of infection based on the history and clinical examination upon presentation.
Microcytosis with or without frank anemia suggestive of iron deficiency and at times in association with thrombocytosis in previously well children has been identified as yet another possible trigger [7]. A prospective study performed by Stolz and colleagues in 2007 demonstrated a significant and independent association between severe anemia (arbitrarily defined by the authors as Hgb < 90 g/l) and CVT [11]. Blood work and blood film investigations of our patient did not reveal evidence of severe anemia, however a platelet count of 440 (on the higher end of the normal range) as well as poikilocytosis and microcytic anemia did favor possible iron deficiency as a potential contributor to his CVT. The diagnosis of anemia may however have been obscured in our patient by relative hemoconcentration secondary to significant dehydration and a falsely elevated ferritin in the acute setting [12]. Dehydration and the resulting alterations in cerebral hemodynamics are an additional important treatable risk factor for pediatric CVT [6–10,12]. LB’s decrease in oral intake, as well as his recurrent episodes of emesis likely resulted in significant dehydration. This was suspected to be a major contributing factor to this patient’s extensive cerebral venous sinus thrombosis. Obstructive sleep-disordered breathing and obesity are two clinical conditions that can often co-exist. Obstructive sleep apnea (OSA), a more severe form of sleep-disordered breathing can affect up to 10% of the pediatric population, with adenotonsillar hypertrophy being the most common etiology [13]. OSA in children can lead to behavioral problems, systemic and pulmonary hypertension and other serious morbidities [13]. An examination of the relationship between OSA and in vitro hypercoagulability performed by Guardiola et al. in 2001 showed an association between OSA and global hypercoagulability [14]. Several previous studies also observed increased platelet activation and aggregation as well as increases in plasma fibrinogen concentration and whole blood viscosity in OSA patients [15,16]. A review of the literature by Liak and Fitzpatrick in 2011 found considerable data supporting an association between OSA and a procoagulant state, however the relationship between OSA and individual clotting factors is yet to be determined [17]. In addition, studies in the adult population have found obesity to be associated with impaired fibrinolysis due to elevated levels of plasminogen activator inhibitor, and demonstrated obesity as a risk factor for deep venous thrombosis [18,19]. Thus, LB’s weight of 49.9 kg (98% percentile) at the age of 10 and his severe obstructive sleep apnea as per his polysomnography, were comorbid conditions that were likely contributing etiologies for his CVT.
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The optimal technique in performing a tonsillectomy has been the center of debate with no one procedure having gained universal acceptance. Our patient underwent bipolar tonsillectomy, similar to the CVT case described by Nix in 2001 [6]. The method of tonsillectomy used by Reilly et al. was not reported [5]. Bipolar cautery is thought to cause minimal thermal damage to the surrounding tissue in comparison to monopolar cuatery/ hot knife, thereby reducing the potential risk of damage to the nearby vessels and the possibility of hypercoagulability. A previous study reported earlier return to normal activity and fewer total doses of pain medication following tonsillectomy with bipolar dissection, in comparison to hot or cold knife cautery [20]. This in theory should allow for improved postoperative hydration, therefore reducing the risk for further complications. In our case however, LB also underwent an adenoidectomy, performed by suction monopolar cautery, which could have lead to surrounding tissue and vascular endothelial thermal injury resulting in a possible hypercoagulable state. 3.2. Clinical manifestations and diagnosis The most common but least specific symptom of CVT found to be present in more than 90% of patients is severe headache which can be one of acute onset or gradually progressive [7–10,12]. CVT can present with a wide spectrum of signs and symptoms and the clinical presentation is affected by the age of the patient, time between onset and presentation, location of CVT and the presence of parenchymal lesions [10,21]. Neurologic signs such as seizures, focal neurological deficits, and loss of consciousness develop in approximately half of the affected patients, with unilateral hemispheric symptoms such as hemiparesis or aphasia being rare occurrences [10]. The key to diagnosis is a high index of suspicion, leading to early imaging and prompt management. Recommendations in the Guidelines on the Investigation, Management and Prevention of Venous Thrombosis in Children published in the British Journal of Hematology in 2011, suggested a prompt MRI including T2 imaging and MRV for diagnosis of both intraparenchymal hemorrhage and sinus thrombosis in children suspected of having CVT [22]. A pre- and post-contrast CT scan with CT venography should be performed as a first line investigation in cases where urgent MRI is unavailable [22]. The imaging should include the petrous temporal bones and air filled sinuses to assess for sinusitis and mastoiditis as potential underlying etiologies [22]. 3.3. Prognosis, recurrence and management Acute cerebral venous thrombosis has been reported to be associated with a 15% overall death rate [21]. However, the majority (90%) of children with CVT survive the initial illness [21]. Seizure at onset, CNS infection, intracranial hemorrhage or infarcts and mental status disorder are some of the long-term predictors of poor prognosis [7–10,12,21]. A European multicenter cohort study performed in 2007, found the overall yearly rate of a second venous thrombosis event in pediatric patients with CVT to be 22.2 per 1000 person-years within a median period of 6 months following the initial CVT [23]. Onset of CVT after age 2 years, failure to recanalize and presence of a factor II mutation were identified as risk factors for recurrent venous thrombosis [23]. Therefore, long-term follow up of affected children is paramount as patients may be at risk of recurrence and often the onset of signs of neurologic injury may be delayed in the pediatric population. Treatment of CVT involves general supportive care such as correction of dehydration and hypovolemia, administration of antibiotic therapy along with source control in the setting
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of infection, management of seizures with anticonvulsants and measures aimed at decreasing intracranial pressure [7–10,12]. According to the recent guidelines published for the treatment of CVT, administration of anticoagulant therapy with the aims of spontaneous thrombus resolution, avoidance of thrombus extension and prevention of pulmonary embolism is an integral part of the therapeutic measure [22]. Based on current evidence, patients with CVT without contraindications for anticoagulation therapy should be treated either with body weight-adjusted subcutaneous LMWH or dose-adjusted intravenous heparin with an at least doubled partial thromboplastin time. Concomitant intracranial hemorrhage related to CVT is not a contraindication for heparin therapy [12,22–24]. There are insufficient data regarding the optimal duration of oral anticoagulant therapy. Oral anticoagulants may be administered for 3 months if the CVT was secondary to a transient risk factor and for 6–12 months in patients with idiopathic CVT and in those with ‘mild’ hereditary thrombophilia. Indefinite anticoagulation should be considered in patients with two or more episodes of CVT or those with ‘severe’ hereditary thrombophilia [21,25]. There is insufficient evidence supporting the use of either systemic or local thrombolysis in patients with CVT, and it may be considered in select cases that deteriorate despite adequate anticoagulation in the absence of intracranial hemorrhage [21,22,25]. Follow up neuroimaging with MRI or CT venography is recommended to be undertaken in the acute phase and during the first year, with some centers performing repeat imaging at 3, 6 and 12 months after diagnosis to assess for evidence of extension, persistence or recanalization [12,22]. 4. Conclusion There is limited information in the Otolaryngology literature about cerebral venous thrombosis, especially as a complication of adenotonsillectomy. This clinical entity is associated with infections of the head and neck, and is likely more common than previously thought. Awareness by the Otolaryngologist and initiation of timely management of preventable risk factors such as severe dehydration or post-operative infection can reduce the risk of this potentially fatal outcome and possible future disability in the patient population. Conflict of interest The authors have no conflicts of interest to declare. References [1] R.F. Baugh, S.M. Archer, R.B. Mitchell, R.M. Rosenfeld, F. Amin, J.J. Burns, et al., Clinical practice guideline: tonsillectomy in children, American Academy of Otolaryngology – Head and Neck Surgery Foundation, Otolaryngol. Head Neck Surg. 144 (1 Suppl.) (2011) S1–S30. [2] D.A. Randall, M.E. Hoffer, Complications of tonsillectomy and adenoidectomy, Otolaryngol. Head Neck Surg. 118 (1998) 61–68. [3] L.B. Johnson, R.G. Elluru, C.M. Myer, Complications of adenotonsillectomy, Laryngoscope 112 (2002) 35–36. [4] R. Subramanyam, A. Varughese, J.P. Willging, S. Sadhasivam, Future of pediatric tonsillectomy and perioperative outcomes, Int. J. Pediatr. Otorhinolaryngol. 77 (2) (2013) 194–199. [5] M.J. Reilly, G. Milmoe, M. Pena, Three extraordinary complications of adenotonsillectomy, Int. J. Pediatr. Otorhinolaryngol. 70 (5) (2006) 941–946. [6] P.A. Nix, Jugular thrombosis following tonsillectomy, J. Laryngol. Otol. 115 (3) (2001) 238–239. [7] G. Sebire, B. Tabarki, D.E. Saunders, I. Leroy, R. Liesner, C. Saint-Martin, et al., Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome, Brain 128 (2005) 477–489. [8] K.S. Carvalho, J.B. Bodensteiner, P.J. Connolly, B.P. Garg, Cerebral venous thrombosis in children, J. Child. Neurol. 16 (8) (2001) 574–580. [9] M.G. Cousser, J.M. Ferro, Cerebral venous thrombosis: an update, Lancet Neurol. 6 (2007) 162–170. [10] J. Stam, Thrombosis of the cerebral veins and sinuses, N. Engl. J. Med. 352 (17) (2005) 1791–1798.
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[11] E. Stolz, J.M. Valdueza, M. Grebe, F. Schlachetzki, E. Schmitt, K. Madlener, et al., Anemia as a risk factor for cerebral venous thrombosis? An old hypothesis revisited, J. Neurol. 254 (2007) 729–734. [12] N. Dlamini, L. Billinghurst, F.J. Kirkham, Cerebral venous sinus (sinovenous) thrombosis in children, Neurosurg. Clin. N. Am. 21 (2010) 511–527. [13] M. Benninger, D. Walner, Obstructive sleep-disordered breathing in children, Clin. Cornerstone 9 (1 Suppl.) (2007) S6–S12. [14] J.J. Guardiola, P.J. Matheson, L.C. Clavijo, M.A. Wilson, E.C. Fletcher, Hypercoagulability in patients with obstructive sleep apnea, Sleep Med. 2 (2001) 517– 523. [15] G. Bokinsky, M. Miller, K. Ault, P. Husband, J. Mitchell, Spontaneous platelet activation and aggregation during OSA and its response to therapy with N-CPAP, Chest 108 (1995) 625–630. [16] C. Rangemark, J.A. Hedner, J.T. Carlson, G. Gleerup, K. Winther, Platelet function and fibrinolytic activity in hypertensive and normotensive sleep apnea patients, Sleep 18 (1995) 188–194. [17] C. Liak, M. Fitzpatrick, Coagulability in obstructive sleep apnea, Can. Respir. J. 18 (6) (2011) 338–348. [18] J.B. McGill, D.J. Schneider, C.L. Arfken, C.L. Lucore, B.E. Sobel, Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients, Diabetes 43 (1995) 104–109.
[19] P.D. Stein, A. Beernath, R.E. Olsen, Obesity as a risk factor in venous thromboembolism, Am. J. Med. 118 (9) (2005) 978–980. [20] M.P. Pizzuto, L. Brodsky, L. Duffy, J. Gendler, E. Nauenberg, A comparison of microbipolar cautery dissection to hot knife and cold knife cautery tonsillectomy, Int. J. Pediatr. Otorhinolaryngol. 52 (3) (2000) 239–246. [21] M.G. Bousser, J.M. Ferro, Cerebral venous thrombosis: an update, Lancet Neurol. 6 (2007) 162–170. [22] E. Chalmers, V. Ganesen, R. Liesner, S. Maroo, T. Nokes, D. Saunders, et al., Guideline on the investigation, management and prevention of venous thrombosis in children, Br. J. Haematol. 154 (2) (2011) 196–207. [23] G. Kent, F. Kirkham, T. Niederstadt, A. Heineche, D. Saunders, M. Stoll, et al., Risk factors for recurrent venous thromboembolism in the European collaborative paediatric database on cerebral venous thrombosis: a multicenter cohort study, Lancet Neurol. 6 (7) (2007) 595–603. [24] P. Monagle, A. Chan, P. Massicotte, E. Chalmers, A.D. Michelson, Antithrombotic therapy in children: the seventh ACCP conference on antithrombotic and thrombolytic therapy, Chest 126 (3 Suppl.) (2004) S645–S687. [25] K. Einhaupl, J. Stam, M.G. Bousser, S.F. De Bruijn, J.M. Ferro, I. Martinelli, et al., EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients, Eur. J. Neurol. 17 (10) (2012) 1229–1235.
