Intravenous lipid emulsion as rescue therapy in severe quetiapine overdose: A case report

Abstract

Severe quetiapine overdose may lead to central nervous system depression and cardiovascular instability; however, refractory distributive shock is an uncommon and life-threatening presentation. Intravenous lipid emulsion has emerged as a potential adjunctive therapy in intoxications caused by highly lipophilic drugs, although evidence remains limited. We report the case of a 25-year-old woman with intentional ingestion of approximately 4.5 g of quetiapine, who developed progressive neurological deterioration and refractory distributive shock despite mechanical ventilation and dual vasopressor support. Laboratory findings showed severe metabolic acidosis with hyperlactataemia, and echocardiography revealed a hyperdynamic profile with reduced systemic vascular resistance. Given the persistence of haemodynamic instability and neurological impairment, a 20% intravenous lipid emulsion was administered as rescue therapy. Within three hours, the patient exhibited marked neurological improvement, with recovery of consciousness (Glasgow Coma Scale score 14/15), along with progressive haemodynamic stabilization allowing discontinuation of vasopressors. Lactate levels normalized within 9 h, and the patient was successfully extubated at 24 h, with no treatment-related adverse events. This case highlights the potential role of intravenous lipid emulsion as an adjunctive rescue therapy in severe quetiapine intoxication with refractory haemodynamic and neurological compromise. Although causality cannot be definitively established, the temporal association and rapid clinical response support its consideration when conventional supportive measures are insufficient.

1. Introduction

Suicide represents a major public health concern, with more than 700,000 deaths reported annually worldwide [1]. Intentional self-poisoning remains an important toxicological manifestation of suicidal behavior, and a recent systematic review of suicidal self-poisoning deaths showed that the substances involved vary across countries, with frequent involvement of prescription drugs and other toxic agents [2]. Among self-harm attempts, intentional drug overdoses are particularly relevant when they involve psychotropic medications chronically prescribed for mood and personality disorders [3].

Currently, toxicity induced by local anesthetics is managed with lipid emulsion therapy, which is traditionally used for parenteral nutrition [4]. Supportive treatments aimed at mitigating cardiovascular and central nervous system manifestations caused by toxicity from other substances, including neuropsychiatric drugs lacking a specific antidote, include activated charcoal, gastric lavage, fluid resuscitation, sodium bicarbonate, inotropic agents, vasopressors, antiarrhythmic drugs, and defibrillation [5], [6]. However, when supportive measures fail to improve symptoms associated with neuropsychiatric drug toxicity, lipid emulsion has been reported as an effective adjunctive therapy for severe central nervous system and cardiovascular manifestations induced by toxic doses of antipsychotics and antidepressants [5], [6], [7].

Quetiapine is an atypical antipsychotic associated with a lower risk of extrapyramidal symptoms compared with first-generation agents. Its pharmacodynamic profile includes antagonism of the 5-hydroxytryptamine receptor 2 A (5-HT2A), dopamine receptor D2 (D2), histamine receptor H1 (H1), alpha−1 adrenergic receptor (α1), and muscarinic receptor M1 (M1) [8]. In overdose settings, antidepressants such as amitriptyline and fluoxetine, as well as antipsychotics including quetiapine and haloperidol, can induce prolongation of the corrected QT interval (QTc), predisposing to torsades de pointes, ventricular fibrillation, and cardiac arrest [9]. The exacerbation of these effects may result in profound sedation, coma, hypotension, tachycardia, seizures, rhabdomyolysis, metabolic disturbances, and, in severe cases, death [8], [10].

Intravenous lipid emulsions, initially developed for nutritional support, have demonstrated efficacy in reversing cardiovascular collapse secondary to systemic toxicity from local anesthetics and tricyclic antidepressants. In recent years, multiple case reports and a recent narrative review have documented their utility as adjunctive therapy in intoxications involving lipophilic neuropsychiatric drugs, with improvements in Glasgow Coma Scale (GCS) scores and reversal of hemodynamic instability [11], [12]. In 2008, the first successful resuscitation using lipid emulsion for non-local anesthetic toxicity was reported [13], describing a case of refractory cardiac arrest due to toxic doses of bupropion (an antidepressant) and lamotrigine (an anticonvulsant) [13]. Since then, benefits of SMOFlipid have been reported in improving GCS scores and QTc prolongation in clozapine toxicity [12], as well as the use of Intralipid in acute toxicity caused by various non-local anesthetics [14]. Additionally, experimental studies have shown that lipid emulsion reduces recovery time from anesthesia with sevoflurane and isoflurane in animal models, suggesting a pharmacologically mediated effect [15]. The available evidence remains limited, as randomized controlled trials evaluating lipid emulsion in neuropsychiatric drug-induced toxicity in humans are not feasible due to ethical constraints [16].

In this context, we present the case of a young female patient with severe quetiapine overdose who developed distributive shock and significant neurological impairment, and who exhibited rapid clinical recovery following administration of 20% intravenous lipid emulsion.

2. Case presentation

A 25-year-old woman with a history of anxiety-depressive disorder under psychiatric follow-up, treated on an outpatient basis with quetiapine 150 mg/day, clonazepam 2.5 mg/day, and fluoxetine 40 mg/day, and with a history of two previous suicide attempts, was found at home with decreased level of consciousness, alongside empty quetiapine blister packs. An intentional ingestion of approximately 4.5 g was estimated in the context of suicidal ideation.

Upon arrival at the emergency department, the patient had an initial GCS score of 10/15 (eye opening [E] = 2, verbal response [V] = 3, motor response [M] = 5), with no clinical evidence of associated trauma. During the first hours, she developed neurological deterioration with a GCS of 8/15 (E1 V2 M5), prompting advanced airway management and orotracheal intubation. After initiation of mechanical ventilation, sedation was discontinued to reassess neurological status; however, impaired consciousness persisted, with bilateral hyporeactive mydriasis.

Initial evaluation included a non-contrast cranial computed tomography (CT), which excluded acute intracranial lesions, and a chest CT, which revealed findings consistent with aspiration pneumonia. Arterial blood gas analysis on admission demonstrated moderate metabolic acidosis, with pH 7.33 (institutional reference range, 7.35–7.45), bicarbonate 19.4 mmol/L (21–26 mmol/L), base excess −6.9 mmol/L (−2 to +2 mmol/L), lactate 0.8 mmol/L (0.5–1.6 mmol/L), PaO₂ 110 mmHg (70–100 mmHg), PaCO₂ 35.9 mmHg (35–45 mmHg), and oxygen saturation 98.5% (96–100%). Complete blood count showed leukocytes 5.53 × 10 ³ /µL (4–10 ×10 ³/µL), hemoglobin 13.1 g/dL (11–15 g/dL), hematocrit 36.4% (37–47%), and platelets 369 × 10 ³ /µL (150–450 ×10 ³/µL), without leukocytosis, anemia, or thrombocytopenia. Serum biochemistry revealed preserved renal and hepatic function, with urea 18.6 mg/dL (16.6–48.5 mg/dL), creatinine 0.59 mg/dL (0.5–0.9 mg/dL), total bilirubin 0.33 mg/dL (0–1.2 mg/dL), AST 15 U/L (10–35 U/L), ALT 19.1 U/L (10–35 U/L), alkaline phosphatase 66.6 U/L (40–129 U/L), and GGT 22.2 U/L (5–36 U/L). Glucose was 133 mg/dL (74–106 mg/dL), sodium 143.9 mmol/L (136–145 mmol/L), chloride 109.3 mmol/L (98–107 mmol/L), and potassium 3.24 mmol/L (3.5–5.1 mmol/L), consistent with mild hypokalaemia. Coagulation parameters were within normal limits, with prothrombin time 12.9 s (10.2–14.5 s), INR 1.08 (0.9–1.3), and activated partial thromboplastin time 23.8 s (22.3–41.1 s). Pancreatic enzymes showed amylase 83.1 U/L (28–100 U/L) and lipase 66.9 U/L (13–60 U/L), the latter slightly above the upper reference limit. Urinalysis was unremarkable, and pregnancy test was negative. Urine toxicology screening was negative for opiates, cocaine, barbiturates, benzodiazepines, amphetamines, and cannabis, with no evidence of common co-ingestions in the available screening panel. Quantitative plasma quetiapine measurement was not performed because this assay was not available in the institutional emergency laboratory and could not be obtained in real time for acute clinical decision-making. Therefore, the diagnosis was based on the reported intentional ingestion, the presence of empty quetiapine blister packs, the compatible neurological and haemodynamic presentation, and the exclusion of other common substances included in the toxicology screen. The negative benzodiazepine result was interpreted cautiously because standard urine immunoassays may have limited sensitivity for clonazepam and its main metabolite, 7-aminoclonazepam; confirmatory testing by liquid chromatography–tandem mass spectrometry was not available.

During the initial stay in the intensive care unit (ICU), the patient developed haemodynamic instability with hypotension and persistent sinus tachycardia (130 bpm), requiring vasopressor support with vasopressin up to 0.02 IU/min and norepinephrine 0.25 µg/kg/min. Serial blood gas analyses showed persistent metabolic acidosis. At 12:46, arterial blood gas analysis showed pH 7.35, bicarbonate 19.9 mmol/L, base excess −6.3 mmol/L, lactate 1.0 mmol/L, PaO₂ 94.5 mmHg, and arterial oxygen saturation 97.3%; venous blood gas analysis obtained at the same time showed pH 7.32, bicarbonate 17.9 mmol/L, base excess −8.5 mmol/L, lactate 1.0 mmol/L, venous oxygen saturation 78.2%, PCO₂ 34.0 mmHg, and PO₂ 47.9 mmHg. The patient subsequently progressed to severe metabolic acidosis, with pH 7.26, bicarbonate 15.8 mmol/L, base excess −12.1 mmol/L, and peak lactate of 5.2 mmol/L, consistent with tissue hypoperfusion in the setting of distributive shock. Renal function remained preserved, with no increase in creatinine, and no coagulopathy was observed.

Bedside transthoracic echocardiography revealed a hyperdynamic left ventricle with preserved ejection fraction, a cardiac index of 3.6 L/min/m², and a low systemic vascular resistance index (SVRI) of 1533 dyn·s·m²/cm⁵ despite dual vasopressor therapy. These findings were consistent with a hyperdynamic distributive shock pattern. In this context of persistent neurological depression, hyporeactive mydriasis, and cardiovascular collapse refractory to conventional support, intravenous lipid emulsion was administered as rescue therapy.

Intralipid® 20% lipid emulsion (Fresenius Kabi AB, Uppsala, Sweden), composed of soybean oil, egg yolk phospholipids, glycerin, and water for injection, was used. It was administered as an initial bolus of 1.5 mL/kg (90 mL) over one minute, followed by a continuous infusion of 0.25 mL/kg/min for one hour, with a total volume of approximately 900 mL. Hemodynamic parameters, neurological status, and biochemical markers were closely monitored during and after infusion, with no adverse events attributable to lipid therapy.

Within the following three hours, progressive improvement in the level of consciousness was observed, with recovery of spontaneous eye opening and coherent verbal response, reaching a GCS of 14/15 (E3 V5 M6). In parallel, vasopressin and norepinephrine doses were gradually reduced and subsequently discontinued, in accordance with hemodynamic improvement and progressive normalization of serum lactate. Subsequent blood gas analyses showed lactate reduction from the third hour, with full normalization after 9 h. At 24 h, arterial blood gas demonstrated pH 7.40, bicarbonate 21 mmol/L, and lactate 1.0 mmol/L, with preserved renal and hepatic function.

At 24 h after ICU admission, once hemodynamic stability without vasopressors and adequate respiratory mechanics were confirmed, the patient was successfully extubated. She remained clinically stable, without further episodes of hypotension or neurological deterioration. On the fourth day of hospitalization, she was transferred to the psychiatry department for continued management of her underlying anxiety-depressive disorder and suicide risk. The temporal evolution of neurological, hemodynamic, and metabolic parameters is summarized in Table 1.

Table 1.

Clinical, hemodynamic, and metabolic evolution.

Date and time	GCS	Vasopressors	Lactate	pH	HCO₃⁻	BE	Supportive management	Clinical observations
04/05–02:46	10	−	0.8	7.33	19.4	−6.9	Emergency evaluation and laboratory assessment	Admission. Moderate metabolic acidosis. CT scan without abnormalities.
04/05–12:46	8	VP 0.02 IU/min + NE 0.25 µg/kg/min	1.0	7.35	19.9	−6.3	ETI + IMV; sedation held for neurological reassessment	Persistent neurological and hemodynamic impairment.
04/05–17:15	−	VP + NE	5.2	7.26	15.8	−12.1	Ongoing IMV; ICU monitoring	Peak hyperlactatemia. Distributive shock. Hyporeactive mydriasis.
04/05–18:00	−	VP + NE	−	−	−	−	20% lipid emulsion (bolus 1.5 mL/kg + infusion 0.25 mL/kg/min × 1 h)	Rescue therapy initiated because of refractory haemodynamic and neurological compromise
04/05–21:45	11	Progressive reduction	4.9	7.26	15.7	−12.2	IMV; post-ILE monitoring	Persistent severe acidosis with early neurological improvement
05/05–03:23	14	Progressive reduction	1.3	7.30	16.7	−10.7	IMV Vasopressor tapering	Neurological recovery Marked lactate reduction.
06/05–02:14	14	Discontinued	1.0	7.40	21.0	−5.0	Planned extubation; IMV discontinued	Acid-base normalization haemodynamic stability without vasopressors
07/05–03:00	15	−	0.8	7.44	24.6	−0.2	Spontaneous breathing; psychiatric transfer	Sustained clinical stability.

Abbreviations and units: BE, base excess; CT, computed tomography; GCS, Glasgow Coma Scale; HCO₃⁻, bicarbonate; IU, international units; NE, norepinephrine; VP, vasopressin; ETI, endotracheal intubation; IMV, invasive mechanical ventilation; ICU, intensive care unit; ILE, intravenous lipid emulsion. Lactate, HCO₃⁻, and BE values are expressed in mmol/L. Vasopressin dose is expressed in IU/min, and norepinephrine dose in µg/kg/min. A dash (−) indicates not applicable or not available.

3. Discussion

The present case is distinguished by the occurrence of refractory distributive shock, evidenced by progressive hyperlactatemia, the requirement for dual vasopressor support, and a hyperdynamic hemodynamic profile with reduced systemic vascular resistance. This phenotype is not the most commonly described in quetiapine overdose, where isolated neurological depression and sinus tachycardia typically predominate, thereby underscoring the severity of the clinical presentation and the relevance of considering rescue therapies [8]. Unlike other reports in which hemodynamic stability is achieved with prolonged supportive care alone, in this case instability persisted despite mechanical ventilation and significant doses of vasopressors, constituting a clinical scenario comparable to those described in case series that prompted the use of lipid emulsion [6], [11].

Intravenous lipid emulsion has been historically used in systemic toxicity from local anesthetics; however, its application to neuropsychiatric drug toxicity is supported by the lipophilic profile of quetiapine, which has a calculated octanol/water partition coefficient (XLogP) of approximately 2.81 [11], and by shared pharmacological mechanisms, including ion channel interference and functional myocardial depression [5]. In recent narrative reviews, quetiapine has been identified among the antipsychotics most frequently associated with a favorable response following lipid emulsion administration, particularly in the presence of concomitant cardiovascular compromise [11]. The dosing regimen used in this case was extrapolated from recommendations for local anesthetic systemic toxicity, consisting of a 20% lipid emulsion bolus of 1.5 mL/kg followed by infusion at 0.25 mL/kg/min. This extrapolation has limitations, as local anesthetic systemic toxicity usually results from intravascular exposure or rapid systemic absorption, whereas quetiapine overdose follows oral ingestion and involves different absorption, distribution, metabolism, and redistribution kinetics. No established lipid emulsion dosing regimen currently exists for quetiapine toxicity or other non-local anesthetic drug poisonings. Nevertheless, published case reports and reviews have commonly adopted the local anesthetic systemic toxicity regimen in life-threatening intoxications involving lipophilic drugs [4], [5]. Further studies are needed to define appropriate indications, dosing strategies, therapeutic endpoints, and safety limits for lipid emulsion therapy in severe quetiapine overdose. In addition, the negative benzodiazepine screen should be interpreted cautiously, as standard urine immunoassays may not reliably detect clonazepam exposure without confirmatory testing for 7-aminoclonazepam.

The biological plausibility of lipid emulsion therapy in this setting is mainly supported by the lipid shuttle mechanism. According to this model, the lipid phase generated in the intravascular compartment can sequester lipophilic drugs from highly perfused target organs, such as the brain and heart, and promote redistribution toward peripheral compartments, including the liver, skeletal muscle, and adipose tissue, where storage and detoxification may occur. This mechanism is particularly relevant for lipophilic agents such as quetiapine, although the magnitude of this effect in oral quetiapine overdose remains uncertain. In addition to this indirect mechanism, lipid emulsions may exert direct pharmacological effects, including positive inotropic activity, provision of free fatty acids as myocardial energy substrates, attenuation of mitochondrial dysfunction, and modulation of nitric oxide-mediated vasodilation [4]. These mechanisms may act synergistically and provide a plausible explanation for the temporally associated neurological and haemodynamic improvement observed after lipid emulsion infusion, while recognizing that causality cannot be definitively established from a single case [4].

A critical aspect in the interpretation of this case is the temporal relationship between lipid emulsion administration and clinical improvement. Objective neurological recovery and progressive reduction of vasopressor requirements occurred within a relatively short interval following lipid emulsion infusion, a pattern consistently described in other reports of severe intoxications involving lipophilic agents [11], [13]. Nevertheless, it must be acknowledged that this temporal association does not establish definitive causality, as the patient continued to receive intensive supportive care. This limitation is inherent to the available evidence, which is predominantly based on case reports and small series, given the ethical infeasibility of conducting randomized controlled trials in this context.

Compared with supportive management alone reported in previous series of quetiapine overdose, the use of lipid emulsion in this case was associated with a more rapid and favorable clinical course, without documented major adverse events attributable to the intervention. However, the absence of serial electrocardiographic monitoring and plasma drug level measurements limits a comprehensive assessment of its impact on other clinically relevant outcomes, such as QTc prolongation, which is well described in this type of intoxication [9]. The absence of quantitative plasma quetiapine measurement is an important limitation of this case, as it precludes direct confirmation of serum drug concentration and limits pharmacokinetic interpretation of the response to lipid emulsion therapy. Nevertheless, the clinical diagnosis was supported by the documented history of intentional ingestion, empty quetiapine blister packs, a compatible toxidrome, and the absence of detection of other common substances in the toxicology screen.

The risk–benefit balance of lipid emulsion therapy should be considered carefully, particularly in non-local anesthetic drug toxicity, where the supporting evidence remains limited. Reported adverse effects include pancreatitis, acute respiratory distress syndrome, lipaemia-induced laboratory interference, pyrogenic reactions, fat overload, hyperlipidaemia, hematological or coagulation abnormalities, and, with very large doses, obstruction of extracorporeal circuits. In the present case, lipid emulsion was used as rescue therapy after persistent neurological and haemodynamic compromise despite conventional support, with no documented clinical adverse events attributable to lipid therapy.

This case provides additional evidence supporting the use of intravenous lipid emulsion as an adjunctive rescue therapy in severe quetiapine intoxication with refractory hemodynamic and neurological compromise. Nevertheless, its use should be individualized, carefully weighed against potential risks, and integrated within a comprehensive critical care approach until more robust observational evidence allows for a clearer definition of its therapeutic role.

4. Conclusions

Severe quetiapine overdose may be associated with significant neurological impairment and refractory distributive shock, representing a clinical scenario with potentially high mortality. In the present case, the administration of 20% intravenous lipid emulsion as adjunctive rescue therapy was temporally associated with objective neurological improvement, progressive reversal of hemodynamic instability, and normalization of lactic acidosis, without evidence of major treatment-related adverse events. Although the available evidence is limited to case reports and narrative reviews, these findings support the consideration of lipid emulsion therapy in severe intoxications caused by highly lipophilic psychotropic agents such as quetiapine, particularly when standard supportive measures are insufficient.

Ethics approval and consent

Written informed consent was obtained from the patient for publication of this case report. All procedures were conducted in accordance with the Declaration of Helsinki and institutional ethical standards.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of Generative AI and AI-assisted technologies in the writing process

During the preparation of this work, the authors used ChatGPT (OpenAI, GPT−5.3 version) to assist with language review and refinement of lengthy text passages. The tool was used exclusively to improve clarity and linguistic quality. All scientific content, interpretation, and conclusions were developed and verified by the authors. After using this tool, the authors reviewed and edited the text as necessary and take full responsibility for the content of the published article.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability

Data will be made available on request.