Intralipid Outperforms Sodium Bicarbonate in a Rabbit Model of Clomipramine Toxicity

Harvey, Martyn; Cave, Grant

doi:10.1016/j.annemergmed.2006.07.016

Cited by 143 publications

(125 citation statements)

References 26 publications

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“…Haemodynamic performance in both groups may have also been augmented by the known sympathomimetic effect of ketamine, utilised as sedation. We nonetheless elected to use this agent in line with both institutional protocol and previous work denoting minimal observed effect with ketamine infusion in a similar model of tricyclic antidepressant toxicity [6]. Additionally, the principal investigators in the present study were not blinded to the study intervention; therefore, potential for introduced observer or information bias exists.…”

Section: Limitationsmentioning

confidence: 99%

“…There has furthermore been considerable laboratory and some clinical reporting of beneficial effect for ILE in toxicity from other lipophilic agents including calcium channel blockers [3,4], tricyclic antidepressants [5][6][7] and β-blockers [4,[8][9][10]. While the exact mechanism of action for ILE is at present uncertain, three main hypotheses have been forwarded to explain the effects of ILE as antidote.…”

Section: Introductionmentioning

confidence: 99%

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Intravenous Lipid Emulsion Does Not Augment Blood Pressure Recovery in A Rabbit Model of Metoprolol Toxicity

2010

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Intravenous lipid emulsion (ILE) has been demonstrated to be an effective treatment for systemic toxicity associated with local anaesthetics and increasingly non-local anaesthetic agents of high lipophilicity. Effect for ILE has been demonstrated in animal models of propranolol poisoning; however, any benefit for ILE in more hydrophilic β-blockers remains uncertain. We determined to examine the effect of ILE on haemodynamic recovery following induction of hypotension with the relatively hydrophilic β-blocker, metoprolol. Twenty sedated, invasively monitored and mechanically ventilated adult New Zealand white rabbits underwent metoprolol infusion to mean arterial pressure (MAP) 60% baseline. Intravenous rescue was given according to the following groups: 6 mL/kg 20% lipid emulsion or 6 mL/kg 0.9% saline solution over 4 min. Haemodynamic parameters were obtained in 15 min. MAP was 70 (interquartile range (IQR), 58-82) mmHg saline group and 79 (IQR,(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89) mmHg ILE group at baseline, and 38 (IQR, 33-40) mmHg saline group and 41 (IQR, 40-43) mmHg ILE group, respectively, following metoprolol infusion. No statistically significant difference between ILE and saline-treated groups was observed in MAP, or pulse rate, at any time point following rescue therapy. ILE was not effective in reversal of metoprolol-induced hypotension in this rabbit model. These findings lend inferential support for the 'lipid sink' as principal mechanism for the beneficial effect observed with ILE administration in other models of lipophilic β-blocker-induced toxicity.

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Section: Limitationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intravenous Lipid Emulsion Does Not Augment Blood Pressure Recovery in A Rabbit Model of Metoprolol Toxicity

2010

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“…Subsequent preclinical experiments exploring the effect of ILE in lipophilic drug toxicity from a variety of nonlocal anesthetic agents have on balance suggested benefit [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

LIPAEMIC Report: Results of Clinical Use of Intravenous Lipid Emulsion in Drug Toxicity Reported to an Online Lipid Registry

et al. 2014

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The use of intravenous lipid emulsion (ILE) as an antidote has prompted significant academic and clinical interest. Between August 2009 and August 2012, data from cases of ILE use in intoxicated patients in different hospitals on different continents were voluntarily entered into a registry based on the world wide web (www.lipidregistry.org). Here, we report data from this project. Participating centers were given access to the registry following institutional subscription. Specifically sought were details of the individual patients' presenting condition, indications for ILE use, ILE administration regimen, potential complications, and of clinical outcome. Forty-eight uses of ILE were reported from 61 participating centers. Ten cases of local anesthetic systemic toxicity were reported; all (10/10) survived. Thirtyeight cases of intoxication by other agents were reported [30 decreased conscious state, 8 cardiovascular collapse (3 deaths)]. There was an elevation in GCS (p<0.0001) and increased systolic blood pressure (p=0.012) from immediately prior to ILE administration to 30 min after use. One serious and two minor adverse effects of ILE use were recorded in 48 reported cases (one case of bronchospastic reaction, one case of hyperamylasemia and one case of interference with laboratory testing). In this series of cases reported to the registry, improvements were seen for GCS in patients with central nervous system toxicity and in systolic blood pressure in shocked patients over a short time frame after the injection of ILE. Few adverse effects were recorded. Clinical trials and the reporting of drug concentrations after ILE use are necessary to further elucidate the role of ILE in clinical toxicology.

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“…Following this trend of expanding utility, ILE has been shown to be efficacious in the emergency treatment of neurotoxicity and cardiotoxicity that results from a variety of cardiovascular and psychoactive drug classes. Animal studies have established benefit from ILE in various models of toxicity including verapamil [5,6], propranolol [7], amiodarone [8], and clomipramine [9]. Case studies have demonstrated successful use of ILE in haloperidol induced cardiac arrest [10], lamotrigine overdose [11], and in resuscitations of patients with combination ingestions of quetiapine/sertraline [12] and buproprion/lamotrigine [13].…”

Section: Introductionmentioning

confidence: 99%

Intravenous Lipid Emulsion Alters the Hemodynamic Response to Epinephrine in a Rat Model

et al. 2013

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Intravenous lipid emulsion (ILE) is an adjunctive antidote used in selected critically ill poisoned patients. These patients may also require administration of advanced cardiac life support (ACLS) drugs. Limited data is available to describe interactions of ILE with standard ACLS drugs, specifically epinephrine. Twenty rats with intra-arterial and intravenous access were sedated with isoflurane and split into ILE or normal saline (NS) pretreatment groups. All received epinephrine 15 μm/kg intravenously (IV). Continuous mean arterial pressure (MAP) and heart rate (HR) were monitored until both indices returned to baseline. Standardized t tests were used to compare peak MAP, time to peak MAP, maximum change in HR, time to maximum change in HR, and time to return to baseline MAP/HR. There was a significant difference (p=0.023) in time to peak MAP in the ILE group (54 s, 95 % CI 44-64) versus the NS group (40 s, 95 % CI 32-48) and a significant difference (p=0.004) in time to return to baseline MAP in ILE group (171 s, 95 % CI 148-194) versus NS group (130 s, 95 % CI 113-147). There were no significant differences in the peak change in MAP, peak change in HR, time to minimum HR, or time to return to baseline HR between groups. ILE-pretreated rats had a significant difference in MAP response to epinephrine; ILE delayed the peak effect and prolonged the duration of effect of epinephrine on MAP, but did not alter the peak increase in MAP or the HR response.

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Intralipid Outperforms Sodium Bicarbonate in a Rabbit Model of Clomipramine Toxicity

Cited by 143 publications

References 26 publications

Intravenous Lipid Emulsion Does Not Augment Blood Pressure Recovery in A Rabbit Model of Metoprolol Toxicity

Intravenous Lipid Emulsion Does Not Augment Blood Pressure Recovery in A Rabbit Model of Metoprolol Toxicity

LIPAEMIC Report: Results of Clinical Use of Intravenous Lipid Emulsion in Drug Toxicity Reported to an Online Lipid Registry

Intravenous Lipid Emulsion Alters the Hemodynamic Response to Epinephrine in a Rat Model

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