**18. Treatment**

Treatment should focus on conservative approaches including maintenance of airway, breathing, and circulation, oxygen therapy, fluid resuscitation, and diazepam administration to control agitation and seizure [6,14,36]. Patients should be monitored for increased CPK and possible acute renal failure that may happen within the next two days [6,14]. Hemodialysis should be considered in cases with acute renal failure and severe creatinine increase [14]. They may need intubation and ICU admission. Gastrointestinal decontamination should be performed in the patients who have referred within the first two hours post-ingestion and have no contraindications [8,49,50].

In severe toxicities due to ingestion of large amounts of sustained-release drug, multiple dose activated charcoal should be considered if no contraindication exists [6,122]. In cases with resistant shock or asystole, extracorporeal methods may be needed [6,35]. Treatment of liver failure is conservative, as well, and urgent liver transplantation is not feasible in many cases [18]. Intubation/ventilation and administration of naloxone are the treatments for tramadolinduced apnea [45]. In severe cases who have not even seized, experimental therapy with diazepam can be performed which can be of help in mild undiagnosed SS [6,44]. Treatment of SS in also conservative and includes withdrawal of the culpable drug and external cooling. Up to 42% of the patients may need ICU and most of them recover within 12-24 hours [70].

In a clinical study on 122 patients, naloxone administration could induce seizure in tramadolintoxicated patients [75]. Therefore, naloxone should not routinely be administered to treat decreased level of consciousness in tramadol toxicity unless respiratory depression has developed [21,45]. Seizures due to tramadol do not respond to naloxone but improve with administration of benzodiazepines. Naloxone can be considered for treatment of post-seizure complaints [123].

Shadnia et al suggested that because of the low risk of multiple seizures in tramadol toxicity, anticonvulsant treatment should not be routinely given even in those with initial seizures [52]. Stoops et al evaluated naltrexone and showed that it could reverse the opioid-induced effects such as miosis; but, increased the serotonergic and adrenergic effects such as mydriasis [56].

Intravenous lipid emulsion (ILE) can reduce mortality due to acute toxicity of tramadol in rabbits, but increasing the ILE dose may cause reverse effects. In a study on 30 rabbis, ILE reduced tramadol-induced tachycardia when administered within 30 minutes of poisoning and showed positive effects on normalizing mean arterial pressure and diastolic blood pressure but it did not have major effect on systolic blood pressure. Intralipid also prevented tramadol-related seizures in low doses and reduced the frequency of increased CPK with higher doses [124].
