Potential Impact of 3% Hypertonic Saline Infusion on Tramadol Poisoning-Induced Electrocardiogram Changes; a Randomized Clinical Trial

Introduction: Tramadol is a synthetic analgesic with weak mu-opioid receptor agonist activity. Tramadol overdose is associated with adverse cardiac effects due to inhibiting cardiac Na+ and K+ channels. This study aimed to investigate the potential ameliorative role of 3% hypertonic saline on the electrocardiogram (ECG) changes in patients presenting with tramadol poisoning. Methods: This was a single-center, controlled, randomized, single-blind clinical trial. Patients were randomized into the case (received hypertonic saline) and control (received placebo) groups. ECG was obtained twice in each group (upon arrival and following the intervention). Response to therapeutic interventions was evaluated using Wilcoxon Signed Ranks Test. Results: A total of 76 patients were included. The mean age of patients was 24.88 ± 4.29 years, and 62 (81.6%) were male. The mean ingested dose of tramadol was 1673.68 ± 608.85 (range: 550-2750) mg. The number needed to treat and the absolute risk reduction of 3% hypertonic saline in the treatment of wide QRS were 1 (95% CI: 1.00 – 1.00) and 100%, respectively. In the treatment of long QTc, these measures were 1.9 (95%CI: 1.2 – 4.5) and 53.85% (95%CI: 22.00 – 85.69), respectively. Conclusion: Given that hypertonic saline infusion can significantly ameliorate tramadol-mediated ECG changes, including QRS prolongation and QT lengthening, it can be regarded as a potential therapeutic strategy to prevent the development of life-threatening ventricular arrhythmias caused by tramadol toxicity.

[1]  A. Alizadehasl,et al.  Potential Ameliorating Role of Spironolactone in Trastuzumab-induced Cardiotoxicity: A Narrative Review , 2022, International Journal of Medical Toxicology and Forensic Medicine.

[2]  E. Radwan,et al.  Chronic exposure to tramadol induces cardiac inflammation and endothelial dysfunction in mice , 2021, Scientific Reports.

[3]  M. Ghojazadeh,et al.  An Umbrella Review of Clinical Efficacy and Adverse Cardiac Events Associated with Hydroxychloroquine or Chloroquine with or Without Azithromycin in Patients with COVID-19 , 2021, Anesthesiology and pain medicine.

[4]  O. Mehrpour,et al.  A review on tramadol toxicity: mechanism of action, clinical presentation, and treatment , 2021, Forensic Toxicology.

[5]  O. Mehrpour,et al.  Tramadol and the occurrence of seizures: a systematic review and meta-analysis , 2019, Critical reviews in toxicology.

[6]  R. Ghodssi-ghassemabadi,et al.  Association of Admission Blood Glucose Level with Major Adverse Cardiac Events in Acute Coronary Syndrome; a Cohort Study , 2019, Archives of academic emergency medicine.

[7]  M. Khajouei,et al.  Stress Cardiomyopathy (Takotsubo syndrome) Following Accidental Methadone Poisoning; Report of Two Pediatric Cases , 2019, Archives of academic emergency medicine.

[8]  M. Rezai,et al.  Electrocardiographic changes in patients with tramadol-induced idiosyncratic seizures , 2016, Turkish journal of emergency medicine.

[9]  B. Dadpour,et al.  Frequency of Electrocardiographic Abnormalities in Tramadol Poisoned Patients; a Brief Report , 2016, Emergency.

[10]  A. Kaye,et al.  Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. , 2015, Pain physician.

[11]  L. Duran,et al.  Can empirical hypertonic saline or sodium bicarbonate treatment prevent the development of cardiotoxicity during serious amitriptyline poisoning? Experimental research , 2015, Cardiovascular journal of Africa.

[12]  R. Dart,et al.  Electrocardiographic manifestations of tramadol toxicity with special reference to their ability for prediction of seizures. , 2012, The American journal of emergency medicine.

[13]  C. Eken Hypertonic saline: An alternative therapy in TCA overdoses failed to respond sodium bicarbonate , 2008, Clinical toxicology.

[14]  W. Brady,et al.  Electrocardiographic abnormalities associated with poisoning. , 2007, The American journal of emergency medicine.

[15]  S. Grond,et al.  Clinical Pharmacology of Tramadol , 2004, Clinical pharmacokinetics.

[16]  M. Guven,et al.  Differential Effects of Lidocaine and Tramadol on Modified Nerve Impulse by 4-Aminopyridine in Rats , 2003, Pharmacology.

[17]  H. Wellens,et al.  Ventricular tachycardia: diagnosis of broad QRS complex tachycardia , 2001 .

[18]  J. Menegazzi,et al.  Experimental tricyclic antidepressant toxicity: a randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation. , 1998, Annals of emergency medicine.

[19]  M. Laks,et al.  Electrocardiographic criteria for tricyclic antidepressant cardiotoxicity. , 1986, The American journal of cardiology.