|
 
 |
| CASE REPORT |
|
| Year : 2021 | Volume
: 8
| Issue : 1 | Page : 50-52 |
|
Pediatric clonidine poisoning
Dipti Sanklecha, Praveen Palyam Nagendra, Basavaraja Gangasamudra Veerappa, Keshavamurthy Mysore Lakshmikantha
Department of Pediatrics, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India
| Date of Submission | 01-Sep-2020 |
| Date of Decision | 29-Oct-2020 |
| Date of Acceptance | 18-Nov-2020 |
| Date of Web Publication | 08-Jan-2021 |
Correspondence Address:
Dr. Dipti Sanklecha
Department of Pediatrics, Indira Gandhi Institute of Child Health, Bengaluru - 560 029, Karnataka
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/JPCC.JPCC_140_20
Clonidine, a commonly used anti-hypertensive agent, is being increasingly used in the treatment of pediatric behavioral disorders, thus increasing the incidence of pediatric poisoning. Poisoning causes somnolence, respiratory depression, hypotension, sinus bradycardia, and miosis. Clonidine overdose of >0.01 mg/kg causes bradycardia and hypotension and >0.02 mg/kg causes apnea and respiratory depression. A 13-year-old boy presented to us with ingestion of 0.073 mg/kg clonidine. He had only sinus bradycardia and drowsiness, which had resolved without any active interventions. As the life-threatening side effects of clonidine poisoning seem to be very rare even at toxic doses, it can be used safely in the pediatric age group.
Keywords: Bradycardia, clonidine, clonidine toxicity
How to cite this article:
Sanklecha D, Nagendra PP, Veerappa BG, Lakshmikantha KM. Pediatric clonidine poisoning. J Pediatr Crit Care 2021;8:50-2 |
| Introduction | |  |
Clonidine is a commonly used anti-hypertensive agent. Its increasing use in the treatment of pediatric behavioral disorders[1] has increased the incidence of pediatric poisoning.[2] Poisoning causes somnolence, respiratory depression, hypotension, sinus bradycardia, and miosis,[1] the most common being lethargy, miosis, and bradycardia.[2] Ingestion of <0.01 mg/kg causes mild symptoms. Bradycardia and hypotension occur at >0.01 mg/kg. Apnea and respiratory depression occur at >0.02 mg/kg.[3] Others document toxicity after ingestion of only 0.1–0.2 mg.[4]
| Case Report | | |
A 13-year-old, 30 kg, male presented within 30 min of ingestion of 22 clonidine tablets (100 μg) (0.073 mg/kg), as witnessed by his mother. He was a known case of attention deficit and hyperactivity disorder (ADHD) and mixed disorder of conduct and emotions, addicted to tobacco for 18 months. He was taking fluoxetine and risperidone irregularly and was started on 100 μg clonidine daily, 6 days back. On examination, he was conscious, oriented, and afebrile, with pulse rate – 97/min, respiratory rate – 18/min, blood pressure – 118/68 mmHg, and oxygen saturation 98% at room air. Systemic examination was normal. Gastric lavage was done with normal saline in the emergency room, and intake kept nil by mouth and intravenous fluids was started. He was shifted to the pediatric intensive care unit (PICU) as he had developed sinus bradycardia and drowsiness within 1 h of ingestion, which resolved in 19 h. Blood investigations and electrocardiogram were normal. Serum clonidine levels were not done due to financial constraints. No other interventions were taken. He was observed for 48 h in the PICU.
| Discussion | | |
Clonidine, a commonly prescribed imidazoline derivative, mainly used for hypertension, has recently gained popularity in pediatrics for the treatment of ADHD, Tourette syndrome, and sleep disturbances.[1]
The increasing clinical indications have increased its prescribing rates, consequently increasing the incidence of pediatric poisoning.[2] According to the National Poison Data System, unintentional pediatric exposures to alpha-2 agonists increased by 5.9% per year between 2000 and 2011. Clonidine was the most commonly reported agent and with the highest percentage of moderate-to-major outcomes.[5]
Clonidine activates presynaptic alpha-2 receptors, inhibiting norepinephrine (NE), adenosine tri-phosphate, and neuropeptide Y release from the postganglionic sympathetic nerves, causing hypotension. It decreases discharges in the sympathetic preganglionic and postganglionic fibers of the splanchnic nerve and the cardiac nerves, respectively. It also stimulates parasympathetic outflow, which may cause bradycardia due to increased vagal tone and diminished sympathetic drive. Activation of the central nervous system (CNS) imidazoline-1 receptors reduces the sympathetic outflow.[6]
Oral bioavailability of clonidine is about 100%. Peak plasma concentration and maximal hypotensive effect occur 1–3 h post-ingestion. The t1/2 is 6–24 h. Major adverse effects are dry mouth and sedation. Some have marked bradycardia. The effects are frequently dose related.[6]
Accidental or deliberate tablet overdose causes toxicity. Poisoning classically presents with somnolence, respiratory depression, hypotension, bradycardia, and miosis,[1] the most common being lethargy, miosis, and bradycardia.[2] Sinus bradycardia is the usual rhythm.[7] Signs are usually seen within 1 h of ingestion.[8] Altered consciousness usually presents within 1.5 h and cardiovascular effects within 4 h.[1] New findings rarely appear after 4 h.[8]
Ingestion of <0.01 mg/kg causes mild symptoms. Bradycardia and hypotension occur at >0.01 mg/kg. Apnea and respiratory depression occur at >0.02 mg/kg.[3] Others document toxicity after ingestion of only 0.1–0.2 mg.[4]
Ingestion of large amounts may initially cause hypertension, but eventually hypotension, likely related to peak serum concentrations and baseline sympathetic tone prior to ingestion. Since effects of clonidine are serum concentration dependant, unless serum levels are known, we cannot be sure as to which effect will be more, as its anti-hypertensive and sedative effects occur at different serum levels.
Respiratory depression is most common in children and may require mechanical ventilation. Respiratory failure occurs within a few hours of ingestion. Majority of clonidine overdoses do not cause significant symptoms. Invasive interventions are rarely required and only in extreme cases, making supportive care the basis of management.[1]
Patients presenting within 1 h of known or suspected clonidine tablet ingestion should receive activated charcoal orally or through nasogastric tube. In the present case also, the child had presented within 30 min of ingestion followed by immediate stomach wash, which might have reduced the exposure level. Airway must be secured in case of respiratory depression prior to administration. No true antidote exists. Clonidine is not amenable to extracorporeal removal.[1]
Hypotension should be addressed with fluid resuscitation. Agents of choice are dopamine and NE in refractory cases. Dopamine may also improve bradycardia. Studies suggest atropine for bradycardia, but results are inconsistent. Transcutaneous or transvenous pacing is suggested but unsubstantiated for bradycardia with hemodynamic instability. Escalating doses of 0.1–10 mg of naloxone, in case of unprotected airway, reverses secondary endogenous opioid release.[1]
An inter-professional team is necessary as toxicity can impair multiple organs. Cardiovascular or CNS symptoms need PICU monitoring. If toxicity signs are absent within several hours of ingestion, patients can be discharged after observing for 4–8 h, but only after a mental health consultation.[1]
Patients' families should be educated on drug safety and storage, away from the child's reach. Most have a good prognosis with treatment. Delay in seeking treatment may cause cardiac or neurological complications. Deaths are very rare.[1]
In our case, the child was also on fluoxetine, a selective serotonin reuptake inhibitor (SSRI), and risperidone, an atypical anti-psychotic. SSRIs have no major cardiovascular side-effects, do not block alpha-adrenergic or histamine receptors, and are not sedating.[9] Risperidone's alpha-1 receptor blocking property may cause postural hypotension.[10] However, in our case, the child did not develop hypotension despite being on risperidone and an overdose of clonidine.
As the life-threatening side effects of clonidine poisoning seem to be very rare even at toxic doses, it can be used safely in the pediatric age group.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that name and initial will not be published, and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | |
| 2. | Theobald JL, Kostic MA. Poisoning. In: Nelson Textbook of Pediatrics. 21 st ed. Canada: Elseviers Inc.; 2020. p. 502.  |
| 3. | Fiser D, Moss M, Walker W. Critical care for clonidine poisoning in toddlers. Crit Care Med 1990;18:1124-8. |
| 4. | Eddy O, Howell J. Are one or two dangerous? Clonidine and topical imidazolines exposure in toddlers. J Emerg Med 2003;25:297-302. |
| 5. | Spiller H, Hays H, Aleguas A. Overdose of drugs for attention-deficit hyperactivity disorder: Clinical presentation, mechanisms of toxicity, and management. CNS Drugs 2013;27:531-43. |
| 6. | Westfall T, Macarthur H, Westfall D. Adrenergic agonists and antagonists. In: Brunton L, Hilal-Dandan R, Knollmann B, editors. Goodman and Gilman's The Pharmacological Principles of Therapeutics. 13 th ed. New York: McGraw-Hill Education; 2018. p. 202-3. |
| 7. | Osterhoudt KC, Henretig FM. Sinoatrial node arrest following tetrahydrozoline ingestion. J Emerg Med 2004;27:313. |
| 8. | Spiller HA, Klein-Schwartz W, Colvin JM, Villalobos D, Johnson PB, Anderson DL. Toxic clonidine ingestion in children. J Pediatr 2005;146:263. |
| 9. | O'Donnell J, Bies R, Shelton R. Drug therapy of depression and anxiety disorders. In: Brunton L, Hilal-Dandan R, Knollmann B, editors. Goodman and Gilman's The Pharmacological Principles of Therapeutics. 13 th ed. New York: McGraw-Hill Education; 2018. p. 272-3. |
| 10. | Meyer J. Pharmacotherapy of psychosis and mania. In: Brunton L, Hilal-Dandan R, Knollmann B, editors. Goodman and Gilman's The Pharmacological Principles of Therapeutics. 13 th ed. New York: McGraw-Hill Education; 2018. p. 292. |
|
Search Pubmed for