Case Report
Treatment of Severe Amitriptyline Intoxication
With Plasmapheresis
Ebru Kolsal,1* Ishak €Ozel Tekin,2Etem Piskin,3Cumhur Aydemir,4Mehmet Aky€uz,5 Hasan ¸Cabuk,5Nil€ufer Eldes,6and Varim Numanoglu7
1
Department of Pediatric Neurology, Gazi University, Ankara, Turkey
2
Department of Immunology, Zonguldak Karaelmas University, Kozlu, Zonguldak, Turkey
3Department of Pediatrics, Zonguldak Karaelmas University, Kozlu, Zonguldak, Turkey 4
Department of Pediatrics, Zekai Tahir Burak Research Hospital, Ankara, Turkey
5Department of Chemistry, Zonguldak Karaelmas University, Kozlu, Zonguldak, Turkey 6
Department of Pediatrics, Sefa Hospital, Istanbul, Turkey
7
Department of Pediatric Surgery, Zonguldak Karaelmas University, Kozlu, Zonguldak, Turkey
Tricyclic antidepressant poisoning is one of the most common causes of serious intoxication. Here, we report a 2-year-old girl with severe amitriptyline (70 mg/kg) intoxication. She was in comatose, had generalized tonic clonic seizure, ventricular tachycardia, and wide QRS complexes. Although she did not respond to classical therapies, very good clinical response to plasmapheresis was obtained and she developed no complications. Thus, plasmapheresis may be an effective treatment modality in poisoning with drugs, which bind to plasma proteins with high affinity. J. Clin. Apheresis 24:21–24, 2009. VVC2009 Wiley-Liss, Inc.
Key words: amitriptyline; plasmapheresis; intoxication
INTRODUCTION
Tricylic antidepressant drug poisoning continues to be one of the most important causes of poisoning in adults and children [1]. Gastric lavage, activated char-coal, antiarrhytmic, anticonvulsan drugs, bicarbonate infussion can be used as treatment modalities. Here, we report a case with severe amitriptyline intoxication who did not respond to these treatment modalities but dra-matically recovered with plasmapheresis.
A 2-year-old girl was admitted to our hospital with lethargy and seizures. Her relatives estimated that she had taken70 mg/kg amitriptyline (laroxyl) tablets 6 h before admission. The patient weighed 12 kg. Her Glasgow coma score was 4, and the pupils were dilated. The blood pressure was 80/50 mm Hg; heart rate, 130 bpm; respiration rate, 32/min; and tempera-ture, 36.08. The laboratory findings of the patient were: hemoglobin, 9.2 g/dL; hematocrit, 27.6%; white blood cell count, 6,300/mm3; and platelet count, 265,000/ mm3. The electrolyte levels (Ca, Na, K, Mg) and liver and kidney function tests were normal. Electrocardio-graphy showed arrhythmias characterized with ventri-cular tachycardia and wide QRS complexes (Fig. 1). She had generalized tonic clonic seizure, which was stopped with midazolam. Activated charcoal (1 g/kg
per dose) was administered via nasogastric tube and the same dose was repeated at every 6 h. Sodium bi-carbonate infusion (2 mEq/kg) was started for alkalini-zation. After 2 h, she was still in deep coma, and ven-tricular tachycardia and seizure started again. Thus, plasmapheresis was performed for 3 h, using an inter-mittent apheresis device, MCS plus 9,000 (Hemo-netics). To reduce ECV (extra-corporeal volume), 125 mL special pediatric bowel was used, and 750 mL plasma volume was removed in each plasmapheresis session. The drawing and returning flow rate were per-formed at 40 mL per minute. Fresh frozen plasma was used as replacement fluid, and the seizure stopped for 6 h, but the ventricular tachycardia and wide QRS complexes persisted. After 6 h, she had one more gen-eralized tonic clonic seizure, and thus, plasmapheresis was performed again. After the second plasmapheresis,
*Correspondence to: Ebru Kolsal, Faculty of Medicine, Department of Pediatric Neurology, Gazi University, Be·evler/Ankara, Ankara 06500, Turkey. E-mail: ebkut@yahoo.com
Received 7 April 2008; Accepted 21 November 2008 Published online 12 January 2009 in Wiley InterScience (www.interscience.wiley.com).
DOI: 10.1002/jca.20185 V
VC2009 Wiley-Liss, Inc.
QRS complexes were normalized (0.08 s) (Fig. 2). No seizures occurred. Plasma amitriptyline levels before and after the first plasmapheresis session were 4.87 lg/ mL and 0.229 lg/mL by HPLC (Table I), respectively, and before and after the second plasmapheresis session, 0.091 lg/mL and 0.020 lg/mL, respectively (Table II). The cardiovascular and neurologic status of the patient
was normalized on the second day. The patient was discharged from the hospital on the fourth day.
DISCUSSION
Tricyclic antidepressants bound to plasma proteins with high affinity. Moreover, these drugs are not
dial-Fig. 1. First ECG with wide QRS and ventricular tachycardia. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
Fig. 2. ECG after second plasmapheresis with normal QRS segment.
22 Kolsal et al.
TABLE I. Plasma Amitriptyline Levels before and after First Plasmapheresis
Sample RT (min) Area (mm2) Sample 1 18.623 26,525,923 Sample 2 19.357 3,743,454
Sample 1: Amitriptyline level before 1st plasmapheresis (500 lL serum was used for sample 1); Sample 2: Amitriptyline level after 1st plasmapheresis (1500 lL serum was used for sample 2).
[Color table can be viewed in the online issue, which is available at www.interscience.wiley.com.] TABLE II. Plasma Amitriptyline Levels before and after Second Plasmapheresis
Sample RT (min) Area (mm2) Sample 3 19.850 595,347 Sample 4 19.983 396,898
Sample 3: Amitriptyline level before 2nd plasmapheresis (600 lL serum was used for sample 3); Sample 4: Amitriptyline level after 2nd plasmapheresis (1800 lL serum was used for sample 4).
[Color table can be viewed in the online issue, which is available at www.interscience.wiley.com.]
Amitriptyline Intoxication and Plasmapheresis 23
ysable because of their high protein affinity. Plasma-pheresis or hemoperfussion may be tried. Exact fatal serum levels of amitriptyline in children are not known. It has been reported that 1 lg/mL serum amitriptyline level predicts high mortality [2]. Do¨nmez et al. [3] showed that serum amitriptyline concentration was 1.299 lg/mL and 0.843 lg/mL, respectively, pre- and post-hemoperfussion, which was applied at the 12th hour of intoxication with 35% reduction. Nenov et al. [4] observed that serum amitriptyline concentration was 4.03 lg/mL and 1.49 lg/mL, respectively, pre- and post-plasmapheresis with 63% reduction. In our patient, reduction rates of 95 and 78% were determined in the plasma amitriptyline levels after first and second plas-mapheresis respectively. Similarly, Bayrakc¸i et al. [5] reported successful treatment of severe amitriptyline poisoning in three cases by plasma exchange. All of these findings suggest that plasmapheresis is an effec-tive method in severe intoxications of amitriptyline.
In severe intoxications with drugs that bind protein with high affinity, the drug may be eliminated by plas-mapheresis [4]. Respiratory depression, seizure, severe
arrhythmias such as increased QRS interval or ventri-cular tachycardia may be considered criteria in deter-mining for plasmapheresis treatment in amitriptyline intoxication.
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Journal of Clinical Apheresis DOI 10.1002/jca 24 Kolsal et al.
