[Downloaded free from http://www.annals.in on Thursday, March 29, 2018, IP: 109.124.55.98] Letters to Editor
Virendra Kumar Arya, Rajeev Subramanyam Department of Anaesthesia and Intensive Care, Post Graduate Institute of Medical Education and Research, Chandigarh - 160 012, India Address for correspondence: Dr. Virendra Kumar Arya, Department of Anaesthesia and Intensive Care, PGIMER Chandigarh - 160 012, India. E-mail:
[email protected]
REFERENCES 1. 2.
Tegtmeyer K, Brady G, Lai S, Hodo R, Braner D. Videos in Clinical Medicine. Placement of an arterial line. N Engl J Med 2006;354:e13. Mark JB, Slaughter TF. Cardiovascular monitoring. In: Miller RD, Fleisher LA, Johns RA, Savarese JJ, Wiener-Kronish JP, Young WL (eds). Miller’s Anesthesia, Sixth edition, Churchill Livingstone: Philadelphia; 2005. p. 1265-362.
Intravenous ondansetron causing severe bradycardia: Two cases DOI: 10.4103/0971-9784.53433
The Editor, Ondansetron is a selective 5-HT3 serotonin receptor antagonist used in the treatment of post-operative nausea and vomiting. Although cardiovascular adverse effects are rare, there have been reports of atrial fibrillation, cardiac dysrhythmias and fatal ventricular tachycardia following intravenous administration of ondansetron. We report a rare adverse effect of intravenous ondansetron in two cases, presented as extreme bradycardia. An eight-year-old child, weighing 15 kg, presented to a tertiary care hospital with perianal abscess. The pre-anesthetic examination was unremarkable, except for tachycardia (120/ min). Prior to medication, the patient’s blood pressure (BP) was 110/70 mm Hg. A total of two mg of ondansetron was administered, slowly, intravenously. Within two to three minutes, the patient became unconscious, apneic and severely bradycardic. An electrocardiogram (ECG) monitor showed sinus bradycardia with a rate of 16 beats per minute, BP of 110/70 mm Hg. Pre-drawn atropine 0.2 mg was administered intravenously immediately. The patient was ventilated with 100% oxygen using a mask. Within three minutes of IV atropine administration, the patient regained consciousness and was well oriented. The respiratory rate returned to normal and pulse was 130 beats per minute. Vital signs remained stable with no other sequelae. 170
A 60-year-old male, diagnosed with carcinoma of the stomach, was admitted for a total gastrectomy. Routine blood investigations showed hemoglobin levels of 7 gm/dL. But for this finding, he was normal. The patient was intravenously pre-medicated with glycopyrrolate 10 mcg/kg followed by ondansetron 4 mg. Within two minutes of ondansetron administration, the patient’s pulse dropped from 120 to 20/min. This was associated with respiratory arrest and loss of consciousness. Pre-drawn atropine, 0.6 mg, was given intravenously and the patient was ventilated with 100% oxygen using a mask. Within two minutes, he regained full consciousness and his pulse returned to 100 beats per minute with BP 130/80 mm of Hg. His vital signs remained stable. Ondansetron, a selective inhibitor of type 3 serotonin (5-HT3) receptor, is a safe and commonly used antiemetic for prevention and treatment of post-operative nausea and vomiting. However, there have been reports highlighting its possible cardiovascular adverse effects. It has reportedly caused atrial fibrillation within 15 minutes of IV injection,[1] bigeminy with ST segment depression, and sinus bradycardia followed by a slow junctional rhythm with ventricular escape beats.[2] It is also reported to have induced fatal ventricular tachycardia following a 4 mg intramuscular injection in a 14-year-old girl.[3] The administration of 5-HT3 receptor antagonists has been associated with prolongation in the QRS (ventricular depolarization), JT (an independent measure of ventricular repolarization not affected by QRS widening) and QT (the time required for completion of both ventricular depolarization and repolarization) intervals of the ECG. The sub-micromolecular affinity of ondansetron to human ether a-go-go-related gene (HERG) encoded K + channel underlies the prolongation of cardiac repolarization reported for this drug. [4] Drugs like granisetron and dolasetron act on the Na+ and K+ channels to prolong QRS or QT interval, resulting in ventricular arrhythmias. Animal studies have proven that the 5-HT receptors present on the endings of vagal afferent nerves, especially in the left ventricle, are implicated in causing bradycardia via the von Bezold Jarisch Reflex. Being a 5-HT3 antagonist, ondansetron attenuates this reflect. Although animal studies strongly support the role of 5-HT3 antagonists in preventing the Bezold Jarisch Reflex, they are yet to be established in humans. The causality assessment of adverse drug reaction, by Naranjo Algorithm, in both cases, was seven, which is probable. However, the mechanism of this paradoxical extreme bradycardia is not clear. It is probably due to the fact that cardiovascular effects of serotonin receptors are complex and consist of bradycardia or tachycardia, hypotension or Annals of Cardiac Anaesthesia Vol. 12:2 Jul-Dec-2009
[Downloaded free from http://www.annals.in on Thursday, March 29, 2018, IP: 109.124.55.98] Letters to Editor
hypertension, and vasoconstriction or vasodilatation. [5] Thus, in any given patient, blockade of 5-HT3 receptors by ondansetron will produce effects depending upon the pre-existing serotonergic activity in the parasympathetic and sympathetic limbs of the autonomic nervous system. [2] Also, serotonin has been implicated in the inhibition of the sympathetic activity, both centrally via 5-HT1 and 5-HT2 receptors and peripherally via 5-HT3 receptors. We, therefore, postulate that since ondansetron is a selective 5-HT3 receptor antagonist, it has no effect on the central sympathetic activity inhibition mediated by 5-HT1 and 5-HT2 receptors. In conclusion, a rare possibility of encountering paradoxical reaction after IV administration of ondansetron should be borne in mind. The authors suggest judicious use of this drug.
Nisha Afonso, Amit Dang, Viraj Namshikar1, Sahish Kamat1, Padmanabh V Rataboli Departments of Pharmacology and 1Anaesthesia, Goa Medical College, India Address for correspondence: Dr. Amit Dang, Department of Pharmacology, Goa Medical College, Bambolim, Goa - 403 202, India. E-mail:
[email protected]
REFERENCES 1.
2.
3. 4.
5.
Kasinath NS, Malak O, Tetzlaff J. Atrial fibrillation after ondansetron for the prevention and treatment of post operative nausea and vomiting: A case report. Can J Anesth 2003;50:229-31. Baguley WA, Hay WT, Mackie KP, Cheney FW, Cullen BF. Cardiac dysrhythmias associated with the intravenous administration of ondansetron and metoclopramide. Anesth Analg 1997;84:1380-1. Chandrakala R, Vijayashankara CN, Kumar K, Sarala N. Ondansetron induced fatal ventricular tachycardia. Indian J Pharmacol 2008;40:186-7. Kuryshev YA, Brown AM, Wang L, Benedict CR, Rampe D. Interactions of the 5-hydroxytryptamine 3 antagonist class of antiemetic drugs with human cardiac ion channels. J Pharmacol Exp Ther 2000;295:614-20. Saxena PR, Villalón CM. Cardiovascular effects of serotonin agonists and antagonists. J Cardiovasc Pharmacol 1990;15:S17-34.
ABO blood groups and myocardial infarction among Palestinians DOI: 10.4103/0971-9784.53434
The Editor, Myocardial infarction (MI) is a leading cause of death in Palestine. The link between ABO blood groups and MI has previously been reported. Most of these reports Annals of Cardiac Anaesthesia Vol. 12:2 Jul-Dec-2009
found an excess of non-O-blood groups and a deficit of O blood groups among patients with MI.[1,2] This letter aims to document the spectrum of ABO blood groups among Palestinian patients with MI, in two major hospitals, in the Gaza-Strip. Over a period of two years from 2005 to 2007, 637 patients (453 males and 184 females) in the age range of 29-93 years old were admitted to the Heart Unit of Al-Shifa hospital in Gaza and Nasser hospital in KhanYounis. All cases were confirmed by cardiologists and electrocardiograph and biochemical investigations. A Chi-square test (χ2) was used to evaluate the association between non-O blood groups and O blood groups and MI. A blood sample was drawn after obtaining verbal consent from the patients. ABO grouping was determined by testing the unknown red cells against monoclonal anti-A, anti-B, and anti-A,B [LabKit, Barcelona, Spain] using the classic slide method. The spectrum of ABO blood groups among patients with MI for both genders is illustrated in Table 1. The blood group A was the most common (57.1%) and blood group O was the second (30.5%). The frequency of non-O versus O blood groups among the patients was more than two-fold, i.e., 69.5% and 30.5%, respectively. The following general formula A>O>B>AB was obtained among the patients. The X2 value was 10.36, hence, the P-value was less than 0.05 (non-O vs. O blood groups and MI). This finding is consistent with other previous studies.[1,2] However, Saha, et al. (1973)[3] and Nydegger, et al. (2003)[4] found that the O and B blood groups are predominant in patients with MI and may play a role in the pathogenesis of MI. Despite this, one cannot deny the potential importance of genetic factors in pathogenesis of MI. A pressing question remains - do the antigens, A or B, have a role in the etiology of MI? No study has convincingly explained the mechanisms by which either A or B antigens could modify the risk of MI. Most suggestions have been speculative. Table 1: Distribution of ABO blood groups in patients with MI for both genders Blood group A B AB O Total
No. of patients (%) 364 (57.1) 57 (8.9) 22 (3.5) 194 (30.5) 637 (100)
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