**17. Toxicity in children**

**16. Miscellaneous side effects**

112 Toxicology Studies - Cells, Drugs and Environment

**Author Publication**

Barbera et al. [32]

De Decker et al. [88]

Solarino et al. [149]

Ripple et al. [150]

Gheshlaghi et al. [151]

Häkkinen et al. [152]

Randall and Crane et al. [153]

**year**

2013 Case

2007 Case

2009 Case

2000 Case

2009 Case

Mannocchi and assistants reported a case of death due to tramadol and propofol due to advanced severe dyspnea [115]. A report showed nine deaths due to consumption of krypton (a plant material containing ODT and mitragynine) in whom the concentration of ODT was between 0.4 to 4.3 µg/g [116]. Another study reported death due o tramadol because of respiratory depression accompanying GABA A and GABA B1 alpha1 over-expression in the

**Cause of death Co-administration**

**or comorbidity**

Munchausen's syndrome, benzodiazepine

Nicotine, diphenhydramine

venlafaxine, trazodone, quetiapine, lithium, acetaminophen

detected in 18.8% Benzodiazepines in 85.5% and alcohol in

14.5%

Other drug/ medicine in 49%, alcohol in 36%

Carbamazepine C= 61.83 mg/l

\_ Dose=1000 mg

**Dosage or concentration(C)**

C=8 mg/L

C= 6.6 mg/L

C= 0.7 mg/L

5.3 mg/L

Median concentration of

C= 1.85-88.8 mg/L

ambiguus nucleus and medulla oblongata solitary. (Table 3) [117].

**Cause of ingestion**

Intentional overdose

Prescribing multiple drugs

Suicide Respiratory

depression and cardiac arrest

Asystole and multiple organ failure

Seizure activity Alcohol,

Not mentioned Other opioids

Mostly multi organ or liver failure and aspiration pneumonia

Suicide Cardiorespiratory failure

Suicide Cardiopulmonary arrest

**Number of patients**

report

report

report

report

report

2012 117 Accidental in

2014 127 Suicide in

**Table 3.** Studies on deaths related to tramadol poisoning

54.8% Suicide in 31.3% Unclear 13.9%

38% Accidental in 27% Unknown in 35%

Accidental ingestion of tramadol is well tolerated by children [50,71,111]. Side effects of tramadol seem to be more common but milder in children. Vomiting is especially common in them [118]. Riedel and Stockhausen reported that tramadol could cross the blood brain barrier (BBB) in children and suppress the brain [119]. Rectal administration of tramadol resulted in severe CNS depression in a 5-week-old infant which was explained to be due to the decreased kinetic elimination and increased permeability of the BBB [51]. Mazor et al. reported two cases of tramadol toxicity with abnormal neurological findings (both seizures and seizure-like activities) in children [9]. Seizure has been reported after accidental ingestion of 4 mg/kg of tramadol in children [23].

Short-term use of tramadol in lactating mother is not dangerous [120] and the risk of neonatal dependency is low.

Tramadol can cause SS without the effect of any other medication while in the adults the risk is increased if a SSRI is also taken [40]. In an 8-month-old infant with SS, the cause of hospital presentation was epistaxis. Sinus tachycardia, hyperthermia, hypertension, agitation, drows‐ iness, and hyper-reflexia of the lower extremities occurred within the first 24 hours after ingestion of 200 mg of tramadol. Neurologic and cardiovascular effects recovered in two days. The infant was discharged after five days in good condition [121].
