Experimental Tricyclic Antidepressant Toxicity: A Randomized, Controlled Comparison of Hypertonic Saline Solution, Sodium Bicarbonate, and Hyperventilation

McCabe, James L.; Cobaugh, Daniel J.; Menegazzi, James J.; Fata, John G.

doi:10.1016/s0196-0644(98)70009-5

Cited by 87 publications

(43 citation statements)

References 10 publications

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“…Resuscitation treatments were administered following attaining target MAP (nominally time zero) and were repeated at 10 minutes. BIC group animals received 3 mL/kg 8.4% BIC infused over a 60-second interval in line with the work of McCabe et al 8 ILE group animals received 3 mL/kg 20% lipid emulsion over 60 seconds consistent with previous work in this model. 9 LIP group animals received 3 mL/kg LIP solution at 8 mg/mL (i.e., 0.8%) in Dulbecco's phosphatebuffered saline (PBS) without magnesium or calcium.…”

Section: Study Protocolmentioning

confidence: 57%

Comparison of Intravenous Lipid Emulsion, Bicarbonate, and Tailored Liposomes in Rabbit Clomipramine Toxicity

Cave

Harvey

Shaw

et al. 2013

Academic Emergency Medicine

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Objectives: Liposome (LIP)-like lipid dispersions have emerged as useful detoxification vehicles in vitro. The authors compare resuscitation with tailored LIPs, 20% intravenous lipid emulsion (ILE), and sodium bicarbonate (BIC), in a rabbit model of clomipramine toxicity.Methods: Sedated, instrumented New Zealand white rabbits underwent clomipramine infusion at 3.2 mg/kg/min to 50% baseline mean arterial pressure (MAP) and then at 1.6 mg/kg/min for 30 minutes. BIC (3 mL/kg 8.4%), ILE (3 mL/kg 20%), or LIP (24 mg/kg) were infused as rescue treatments at toxicity and were repeated at 10 minutes (n = 5 in each group). remains a difficult therapeutic challenge. Mainstays of therapy include aggressive supportive care and sodium bicarbonate (BIC)-initiated systemic alkalinization. 1 More recently, intravenous lipid emulsion (ILE) preparations have been forwarded as adjuncts to standard management of TCA toxicity with successful reports of use in animal models 2 and human subjects. 3 Both pharmacokinetic and pharmacodynamic mechanisms have been forwarded to explain the beneficial effects of ILE. The widely held lipid sink theory is that lipid sequesters certain xenobiotics (such as TCAs) and reduces toxicity by decreasing the free serum concentration of the offending toxin. 4,5 Liposomes are spherical vesicles of phospholipids and effectively sequester amitriptyline and imipramine in vitro. 6,7 Specific advantages afforded by liposomes (LIPs) include increased surface area:volume ratios, the ability to modulate surface charge and internal pH, and the inherent lipid bilayer structure. To date, however, there are limited data on the antidotal efficacy of liposomal formulations in intact animal models.We examined the effect of LIPs in an established animal model of TCA toxicity. Specifically, in this study we compare resuscitation with bicarbonate (BIC), ILE, and LIPs in a previously studied rabbit model of clomipramineinduced shock. METHODS Study DesignThis was a laboratory study of clomipramine-induced cardiotoxicity in a rabbit model. The study was approved by the institutional ethics committee of the

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Section: Study Protocolmentioning

confidence: 57%

Comparison of Intravenous Lipid Emulsion, Bicarbonate, and Tailored Liposomes in Rabbit Clomipramine Toxicity

Cave

Harvey

Shaw

et al. 2013

Academic Emergency Medicine

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“…20 We also have reported improvement in cardiotoxicity from administration of sodium bicarbonate in a swine model of verapamil poisoning, which also may involve sodium channel blockade. 18 Conversely, though animals receiving hypertonic sodium bicarbonate (experimental group) in this report experienced a significant increase in plasma Na ϩ concentration, pH and BE, we could not detect a narrowing of the QRS interval.…”

Section: Discussionmentioning

confidence: 79%

Hypertonic Sodium Bicarbonate for Taxus media-induced Cardiac Toxicity in Swine

et al. 2002

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Abstract. Objective: To determine whether intravenous (IV) hypertonic sodium bicarbonate is effective in the reversal of QRS widening associated with severe Taxus intoxication. Methods: Seventeen anesthetized and instrumented swine were poisoned with an IV extract of Taxus media until doubling of the QRS interval on electrocardiography was achieved. After poisoning (time zero), the animals received either 4 mL/kg IV 8.4% sodium bicarbonate (experimental group; 6 animals), a similar volume of 0.7% NaCl in 10% mannitol (mannitol group; 6 animals), or nothing (control group; 5 animals). The main outcome parameter was QRS duration. Secondary outcome parameters were mean arterial pressure (MAP), heart rate (HR), and cardiac index (CI = cardiac output/kg). Additionally, arterial pH, partial pressure of carbon dioxide (pCO 2 ), and plasma-ionized calcium, sodium, and potassium were monitored. Results: Taxus toxicity, defined as a 100% increase in QRS duration, was produced in all animals. The an-

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“…All animals were prepared and instrumented in the same fashion and randomly assigned to three treatment arms. This model was adapted from that described by McCabe et al [7].…”

Section: Methodsmentioning

confidence: 99%

“…Using a swine model of severe nortriptyline poisoning developed by McCabe et al, the purpose of this study was to determine if amiodarone, a class III antidysrrhythmic, had harmful hemodynamic effects on a wide-complex tachycardia [7]. The null hypothesis is that there would be no difference in the QRS complex or mean arterial pressure between TCA-poisoned subjects treated with amiodarone and those treated with hypertonic sodium bicarbonate, the standard of care for known TCA poisoning.…”

Section: Effects Of Amiodarone In a Swine Model Of Nortryptiline Toximentioning

confidence: 99%

Effects of amiodarone in a swine model of nortryptiline toxicity

et al. 2006

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Objectives: Antiarrhythmics can have devastating effects in cardiotoxic poisonings. Amiodarone is recommended for treatment of wide complex tachycardia, but its hemodynamic effects in wide complex tachycardia induced by tricyclic antidepressant poisoning are unknown. The objective of this study was to compare the effects of sodium bicarbonate, amiodarone, and normal saline in treating wide complex tachycardia secondary to nortriptyline poisoning.Methods: This unblended randomized controlled animal study involved 18 anesthetized, intubated pigs with arterial and venous lines. Nortriptyline (2 mg/mL) was infused at 20 mg/min until the onset of toxicity, defined as a systolic blood pressure ≤50 mmHg or QRS ≥120 ms. At that point, the pigs were randomized into three groups of six. Group I received 0.9% normal saline, 10 ml/kg. Group II received hypertonic sodium bicarbonate, 1 mEq/kg. Group III received amiodarone, 15 mg/kg. The pigs were observed until death or survival at 60 minutes.Results: After treatment, the changes in QRS were as follows: Group I, −2.0 ms; Group II, −33.0 ms; Group III, −21.7 ms. ANOVA demonstrated no significant difference between the groups (p = 0.28). Mean arterial pressures 10 minutes after treatment were as follows: Group I, 19.4 mmHg; Group II, 23.7 mmHg; Group III, 12.5 mmHg. Based on ANOVA, there was no significant difference between any of the groups (p = 0.50).Conclusions: In this model of nortriptyline poisoning, the administration of amiodarone to correct wide complex tachycardia did not have a harmful effect.

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Experimental Tricyclic Antidepressant Toxicity: A Randomized, Controlled Comparison of Hypertonic Saline Solution, Sodium Bicarbonate, and Hyperventilation

Cited by 87 publications

References 10 publications

Comparison of Intravenous Lipid Emulsion, Bicarbonate, and Tailored Liposomes in Rabbit Clomipramine Toxicity

Comparison of Intravenous Lipid Emulsion, Bicarbonate, and Tailored Liposomes in Rabbit Clomipramine Toxicity

Hypertonic Sodium Bicarbonate for Taxus media-induced Cardiac Toxicity in Swine

Effects of amiodarone in a swine model of nortryptiline toxicity

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