Summary: I present the case of a healthy 17-year-old girl that nearly died from an amitriptyline overdose and how the use of intralipid could be responsible for saving her life.
Case Report:
The patient was found at home unresponsive by her mother, she was brought into the A&E resus department, GCS 3, having had two witnessed, self-terminating seizures before the paramedics arrived, and a further seizure on-route to the hospital.
She was tachycardic, sweating, with dilated unreactive pupils. There was no history of epilepsy, head injury, depression or previous suicide attempts. In fact she had just achieved 9 A*s for her GCSEs.
Her ECG showed a sinus tachycardia. Full blood count, coagulation, urea and electrolytes were normal. Arterial Blood gas showed: pH 6.8, pCO2 9.0, pO2, 65, HCO3 17.
Hypoventilating and unable to protected her airway she was intubated and ventilated. A CT head scan was performed which showed no abnormality. At this point the patient was transferred to ITU for further supportive treatment.
Collateral history from the family told us that the patient prepared her grandmother’s tablets for her – including amitriptyline, and that her cousin had recently taken an overdose, but made a complete recovery without complications. A search of her bedroom found several empty boxes of amitriptyline and we suspected that she had taken between 7.5 and 10g.
Management: Arterial and central lines were inserted to allow invasive monitoring and drug administration. The patient was becoming increasingly unstable. Toxbase was consulted for advice and accordingly 8.4% sodium bicarbonate was administered, aiming to correct the pH to 7.5.
Despite optimal fluid filling, noradrenaline was required to maintain a systolic blood pressure >70mmHg.
In spite of achieving blood pH of 7.5, ECG changes progressed with more pronounced lengthening of PR, QRS and QT segments. There were several runs of self terminating VT seen on the monitor.
Toxbase was reviewed again and strongly advised against administering antiarrhythmic drugs as they have often worsened similar situations.
Magnesium Sulphate was administered as it possessed multiple antiarrhythmic properties and was considered safe by Toxbase. Unfortunately this had no effect and further cardiac instability occurred.
Clutching at straws we tried Intralipid. At the time this was only briefly mentioned on Toxbase (pre AAGBI guidance on local anaesthetic toxicity). A bolus of 1.5ml/kg of 20% intralipid (75ml) followed by an infusion of 0.5ml/kg/min up to a total volume of 1000ml.
Within 10mins, no further runs of VT were seen; within an hour ECG changes had reverted to sinus tachycardia. Within 12 hours GCS was improving and within 16 hours the patient had regained consciousness and was extubated. The next day the patient was discharged from ITU to a medical ward.
Discussion: Tricyclic antidepressants (TCAs), such as amitriptyline, are prescribed in the UK for problems including depression, anxiety and chronic pain. TCA overdose accounts for up to 18% of all poisoning deaths in the UK4. In 2005 there were 272 deaths in the UK related to TCA overdose5. TCAs block α-adrenergic receptors and have anticholinergic effects. This leads to cardiovascular effects including sinus tachycardia, cardiac arrhythmias, vasodilatation, hypotension and asystole. They exert a number of effects on the central nervous system, leading to drowsiness and ultimately coma, respiratory depression and seizures4; 6-7.
There is limited literature evidence for the use of intralipid for TCA overdose. A search of Medline and Embase (tricyclic antidepressant and lipid emulsion filters) generated 23 papers, 3 relevant animal studies and 1 study of healthy volunteers. There were no randomised control trials and only 1 case series of the use of lipid emulsion in the clinical environment. The majority of supporting evidence comes from single case reports showing favourable outcomes where conventional therapies have failed to achieve cardiac stability.
Amitriptyline is highly lipophilic. The theory is that an infusion of 20% lipid emulsion creates an intravascular lipid compartment; thus reducing the amitriptyline absorption by the tissues and potentially reversing the process8-10.
The study involving the healthy volunteers showed decreased absorption of amitriptyline by the tissues and no harmful effects from the lipid infusion10 although other papers have highlighted problems with blood investigations and lipidaemia.
The latest recommendations are that an infusion of lipid rescue should be considered in cases of TCA overdose that are refractory to usual medical management3.
Lessons Learnt: TCA overdose is a potentially life threatening condition. Even a healthy, young patient can deteriorate rapidly, stop responding to treatment and ultimately die. Toxbase offers a wealth of information about poisons and their management. It was a vital resource to myself and the team in treating this young patient. The literature evidence is still limited but would suggest that an intralipid infusion could reduce TCA absorption into the tissues, preventing further deterioration with possibly no increased morbidity associated with the infusion itself.
References: 1) www.toxbase.org 2010 2) www.lipidrescue.org 2010 3) Body R et al. Guidelines in Emergency Medicine Network (GEMNet): guideline for the management of Tricyclic antidepressant overdose. Emergency Medicine Journal 2011; 28(4):347-368 4) Kerr GW et al. Tricyclic antidepressant overdose: a review. Emergency Medicine Journal 200; 18: 236-41 5) National Statistics. The controller of HMSO. 2008. www.statistics.gov.uk 6) Brennan FJ. Electrophysiological effects of imipramine and doxepin on normal and depressed cardiac Purkinje fibres. American Journal of Cardiology 1980; 46: 599-606 7) Shannon M et al. Hypotension in severe Tricyclic antidepressant overdose. American Journal of Emergency Medicine 1988; 6: 439-442 8) Weinberg G et al. Lipid emulsion infusion rescues dogs from bupivacaine induced cardiac toxicity. Reg anesth Pain Med 2003; 28: 198-202 9) Harvey et al. Intralipid outperforms sodium bicarbonate in a rabbit model of clomipramine toxicity. Annals of Emergency Medicine 2007; 49: 178-85 10) Minton et al. The effect of a lipid suspension on amitriptyline disposition. Arch Toxicology 1987; 60: 467-9
M J Milsom
CT 2 Anaesthetics, Pinderfields Hospital, Mid Yorkshire Hospitals NHS Trust
Summary:
I present the case of a healthy 17-year-old girl that nearly died from an amitriptyline overdose and how the use of intralipid could be responsible for saving her life.
Case Report:
The patient was found at home unresponsive by her mother, she was brought into the A&E resus department, GCS 3, having had two witnessed, self-terminating seizures before the paramedics arrived, and a further seizure on-route to the hospital.
She was tachycardic, sweating, with dilated unreactive pupils. There was no history of epilepsy, head injury, depression or previous suicide attempts. In fact she had just achieved 9 A*s for her GCSEs.
Her ECG showed a sinus tachycardia. Full blood count, coagulation, urea and electrolytes were normal. Arterial Blood gas showed: pH 6.8, pCO2 9.0, pO2, 65, HCO3 17.
Hypoventilating and unable to protected her airway she was intubated and ventilated. A CT head scan was performed which showed no abnormality. At this point the patient was transferred to ITU for further supportive treatment.
Collateral history from the family told us that the patient prepared her grandmother’s tablets for her – including amitriptyline, and that her cousin had recently taken an overdose, but made a complete recovery without complications. A search of her bedroom found several empty boxes of amitriptyline and we suspected that she had taken between 7.5 and 10g.
Management:
Arterial and central lines were inserted to allow invasive monitoring and drug administration. The patient was becoming increasingly unstable. Toxbase was consulted for advice and accordingly 8.4% sodium bicarbonate was administered, aiming to correct the pH to 7.5.
Despite optimal fluid filling, noradrenaline was required to maintain a systolic blood pressure >70mmHg.
In spite of achieving blood pH of 7.5, ECG changes progressed with more pronounced lengthening of PR, QRS and QT segments. There were several runs of self terminating VT seen on the monitor.
Toxbase was reviewed again and strongly advised against administering antiarrhythmic drugs as they have often worsened similar situations.
Magnesium Sulphate was administered as it possessed multiple antiarrhythmic properties and was considered safe by Toxbase. Unfortunately this had no effect and further cardiac instability occurred.
Clutching at straws we tried Intralipid. At the time this was only briefly mentioned on Toxbase (pre AAGBI guidance on local anaesthetic toxicity). A bolus of 1.5ml/kg of 20% intralipid (75ml) followed by an infusion of 0.5ml/kg/min up to a total volume of 1000ml.
Within 10mins, no further runs of VT were seen; within an hour ECG changes had reverted to sinus tachycardia. Within 12 hours GCS was improving and within 16 hours the patient had regained consciousness and was extubated. The next day the patient was discharged from ITU to a medical ward.
Discussion:
Tricyclic antidepressants (TCAs), such as amitriptyline, are prescribed in the UK for problems including depression, anxiety and chronic pain. TCA overdose accounts for up to 18% of all poisoning deaths in the UK4. In 2005 there were 272 deaths in the UK related to TCA overdose5. TCAs block α-adrenergic receptors and have anticholinergic effects. This leads to cardiovascular effects including sinus tachycardia, cardiac arrhythmias, vasodilatation, hypotension and asystole. They exert a number of effects on the central nervous system, leading to drowsiness and ultimately coma, respiratory depression and seizures4; 6-7.
There is limited literature evidence for the use of intralipid for TCA overdose. A search of Medline and Embase (tricyclic antidepressant and lipid emulsion filters) generated 23 papers, 3 relevant animal studies and 1 study of healthy volunteers. There were no randomised control trials and only 1 case series of the use of lipid emulsion in the clinical environment. The majority of supporting evidence comes from single case reports showing favourable outcomes where conventional therapies have failed to achieve cardiac stability.
Amitriptyline is highly lipophilic. The theory is that an infusion of 20% lipid emulsion creates an intravascular lipid compartment; thus reducing the amitriptyline absorption by the tissues and potentially reversing the process8-10.
The study involving the healthy volunteers showed decreased absorption of amitriptyline by the tissues and no harmful effects from the lipid infusion10 although other papers have highlighted problems with blood investigations and lipidaemia.
The latest recommendations are that an infusion of lipid rescue should be considered in cases of TCA overdose that are refractory to usual medical management3.
Lessons Learnt:
TCA overdose is a potentially life threatening condition. Even a healthy, young patient can deteriorate rapidly, stop responding to treatment and ultimately die. Toxbase offers a wealth of information about poisons and their management. It was a vital resource to myself and the team in treating this young patient. The literature evidence is still limited but would suggest that an intralipid infusion could reduce TCA absorption into the tissues, preventing further deterioration with possibly no increased morbidity associated with the infusion itself.
References:
1) www.toxbase.org 2010
2) www.lipidrescue.org 2010
3) Body R et al. Guidelines in Emergency Medicine Network (GEMNet): guideline for the management of Tricyclic antidepressant overdose. Emergency Medicine Journal 2011; 28(4):347-368
4) Kerr GW et al. Tricyclic antidepressant overdose: a review. Emergency Medicine Journal 200; 18: 236-41
5) National Statistics. The controller of HMSO. 2008. www.statistics.gov.uk
6) Brennan FJ. Electrophysiological effects of imipramine and doxepin on normal and depressed cardiac Purkinje fibres. American Journal of Cardiology 1980; 46: 599-606
7) Shannon M et al. Hypotension in severe Tricyclic antidepressant overdose. American Journal of Emergency Medicine 1988; 6: 439-442
8) Weinberg G et al. Lipid emulsion infusion rescues dogs from bupivacaine induced cardiac toxicity. Reg anesth Pain Med 2003; 28: 198-202
9) Harvey et al. Intralipid outperforms sodium bicarbonate in a rabbit model of clomipramine toxicity. Annals of Emergency Medicine 2007; 49: 178-85
10) Minton et al. The effect of a lipid suspension on amitriptyline disposition. Arch Toxicology 1987; 60: 467-9