a) A 75-year-old woman received 20 mL of 0.5% levobupivacaine for a lumbar plexus block. Within seconds she became unresponsive, developed tonic clonic seizures and became hypotensive (60/40 mmHg) with low voltage widened QRS complexes on ECG. She was treated with intravenous metaraminol, endotracheal intubation and 100 mL of intravenous 20% intralipid. Hypotension rapidly resolved, the QRS morphology normalized and her surgery continued uneventfully (Foxall et al, 2007).
b) An 84-year-old woman received 40 mL of 1% (instead of 0.5%) ropivacaine for an axial plexus block. After 15 minutes she became dizzy and drowsy, then lost consciousness and had a tonic clonic seizure. She was ventilated and given thiopental, then developed ventricular extrasystoles, followed by severe bradycardia which progressed to asystole. Cardiopulmonary resuscitation (CPR) was started; she received epinephrine (3 mg total). After 10 minutes of CPR, she received 100 mL of 20% intralipid intravenously as a bolus followed by an infusion of 10 mL/min. After a total dose of 200 mL, she developed a wide complex tachyarrhythmia with palpable pulses and a systolic blood pressure of 100 mmHg. A pacemaker was inserted as a precaution. Further evaluation did not reveal any evidence of myocardial infarction or pulmonary embolism. She was extubated 3 hours after the event and recovered without sequelae (Litz et al, 2006).
c) A 91-year-old man received 30 mL of 1% mepivacaine and 10 mL of 1% prilocaine for a brachial plexus block. Within 5 minutes he became dizzy and nauseated, became agitated then unresponsive. He developed ventricular extrasystoles with intermittent bigeminy and hypertension (190/90 mmHg). He received a bolus of 1 mL/kg intralipid 20% which was repeated after 3 minutes (total dose 100 mL) followed by an infusion at 14 mL/min. He regained consciousness within 5 minutes of intralipid injection, and extrasystoles disappeared after a total dose of 200 mL had been infused. Surgery proceeded uneventfully after that (Litz et al, 2008).
d) An 82-year-old woman received 30 mL of 0.5% ropivacaine with epinephrine for a femoral nerve block, followed by 30 ml of 0.5% bupivacaine with epinephrine for a sciatic nerve block. About 20 seconds after completion of the sciatic block, she had a tonic clonic seizure. She was treated with 3 mg midazolam and bag valve mask ventilation. She had a second seizure about 60 seconds later and then developed ventricular tachycardia at a rate of 200 beats/minute with palpable femoral and carotid pulses. She received 150 mg amiodarone followed by 100 mL of 20% intralipid. She then became hypotensive and received a synchronized countershock at 120 joules. She converted to sinus rhythm, and an additional 400 mL 20% intralipid was infused over 15 minutes. She remained stable thereafter, with a normal mental status by 2 hours after the event (McCutchen & Gerancher, 2008).
e) An elderly woman received 20 mL of 0.5% bupivacaine for a sciatic nerve block, followed by 2.2 mL of 0.75% bupivacaine for spinal anesthesia, and then 20 mL of 0.5% bupivacaine with epinephrine for a lumbar plexus block. Three minutes after the lumbar plexus block, she became nonverbal and had a seizure. She received 1.5 mL/kg (100 mL) of intralipid within 2 minutes and seizure activity stopped; she regained consciousness within 3 to 4 minutes (Whiteside, 2008).
f) A 91-year-old man received 30 mL of 1% mepivacaine and 10 mL of 1% prilocaine preoperatively. Five minutes later the patient experienced dizziness, nausea, and agitation, and became unresponsive. He also developed supraventricular extrasystoles with intermittent bigeminy. Following an intravenous bolus dose of 1 mL/kg of 20% lipid emulsion, repeated 3 minutes later for a total amount of 100 mL, followed by a continuous infusion of 0.25 mL/kg/min (14 mL/min) for a total dose of 200 mL, the patient became responsive, with resolution of his cardiac abnormalities (Litz et al, 2008).
g) An 83-year-old man developed asystolic cardiac arrest after receiving 26 mL of bupivacaine 0.5% preoperatively as a sciatic nerve block for post operative pain management following a total knee arthroplasty. After initially administering chest compressions, the patient received a 250 mL (3 mL/kg) bolus dose of 20% lipid emulsion, intravenously administered over a 2-minute period, followed by a continuous infusion of 0.2 mL/kg/minute. Within 10 minutes, the ECG indicated sinus tachycardia with palpable pulses, and within 90 minutes, the patient was awake and responsive (Smith et al, 2008).

a) A 19-year-old patient developed dysarthria and progressive myoclonus of the upper extremities after unintentionally receiving 50 mL of 2% mepivacaine (1000 mg) instead of the prescribed 50 mL of 1% mepivacaine (500 mg) preoperatively for wrist surgery. Following intravenous administration of 100 mL of 20% lipid emulsion, the patient's symptoms resolved and the surgery was performed uneventfully (Charbonneau et al, 2009).
b) A 24-year-old man received an injection of 40 mL 0.5% ropivacaine through interscalene brachial plexus block during a surgery for a left fractured clavicle. The patient developed restlessness and limb twitching during emergence from anesthesia. Ropivacaine toxicity was suspected and he was given a 100 mL 20% lipid emulsion intravenously. The symptoms of toxicity subsided and he recovered consciousness within 5 minutes of the lipid infusion. Plasma levels of total and protein-unbound ropivacaine measured 2 hours and 20 minutes after surgery were 1.99 and 0.13 mcg/mL, respectively. After lipid emulsion, ropivacaine concentrations decreased to 1.72 and 0.05 mcg/mL, respectively (Mizutani et al, 2011).
c) A 58-year-old man received a 40 mL solution containing 20 mL 0.5% bupivacaine and 20 mL 1.5% mepivacaine for a brachial plexus block. About 30 seconds afterwards, he became incoherent and then had a tonic clonic seizure. He received bag valve mask ventilation and 50 mg propofol. About 90 seconds later he seized again, and received 100 mg propofol. At this point he became asystolic and advanced cardiac life support (ACLS) was started. He received 3 mg epinephrine, 2 mg atropine, 300 mg amiodarone, and 40 units vasopressin as well as monophasic defibrillation four times. His cardiac rhythms included ventricular tachycardia (both with and without a pulse), ventricular fibrillation, and eventually asystole. After 20 minutes of ACLS, he received 100 mL of a 20% lipid emulsion, with continued CPR and a 360 joule defibrillation, followed by atropine 1 mg and epinephrine 1 mg. Within 15 seconds he reverted to sinus rhythm at 90 beats/min with palpable pulses. He received an infusion of 20% lipid emulsion at 0.5 ml/kg/min for 2 hours. He recovered with no neurologic sequelae. He underwent cardiac catheterization, which revealed total occlusion of the right coronary artery with a left ventricular ejection fraction of 32%, and an automatic implantable cardiac defibrillator was inserted (Rosenblatt et al, 2006).
d) A 60-year-old man received 30 mL of 1.5% mepivacaine with epinephrine and 10 mL of 0.5% bupivacaine for a brachial plexus block. Five minutes later he developed labored respirations, followed by apnea and unresponsiveness. He became pulseless, and received CPR, atropine 1 mg, epinephrine 3 mg total, vasopressin 40 units, 100 mL of 8.4% sodium bicarbonate, magnesium sulfate 6 g, and 11 successive defibrillations without return of sustained cardiac activity. He received 250 mL of 20% lipid emulsion over 30 minutes beginning 10 minutes after CPR was started. Hemodynamic stability was eventually achieved and he ultimately recovered. There was no evidence of myocardial infarction or pulmonary embolism (Warren et al, 2008).

a) A 13-year-old girl received a lumbar plexus block with 20 mL of a solution that was equal volumes of 1% lidocaine with epinephrine and 0.75% ropivacaine. After 15 minutes she developed ventricular tachycardia with hypertension (120/92 mmHg) and oxygen saturation decreased to 92%. She was treated with 150 mL (3 mL/kg) of a 20% lipid emulsion and within 2 minutes QRS complexes normalized (with ST depression), hypertension resolved, and oxygen saturation increased to 97%. After 30 minutes ST depression resolved and surgery proceeded uneventfully (Ludot et al, 2008).
b) A 17-year-old adolescent experienced seizures and became pulseless after receiving 20 mL of 0.5% bupivacaine for post operative analgesia. Within 1 to 2 minutes after seizure onset, intravenous midazolam 3 mg followed by 20% lipid emulsion was administered. He developed ventricular fibrillation, and was successfully cardioverted to a narrow complex sinus tachycardia. During the entire resuscitation period, a total of 500 mL 20% lipid emulsion (approximately 8 mL/kg) was administered. The patient's cardiac status stabilized and daily follow-up for 1 week indicated no evidence of sequelae (Markowitz & Neal, 2009).

a) An 18-year-old pregnant woman (38 weeks gestational age) received 10 mL of 0.5% bupivacaine for epidural anesthesia. Within 90 seconds she became restless and agitated, followed by twitching then unresponsiveness. Aspiration of the epidural catheter revealed venous blood. She received two 50 mL boluses of 20% intralipid, and then 100 mL as an infusion. Within 30 seconds she regained consciousness. She recovered completely, and both mother and neonate were discharged on postoperative day 4 (Spence, 2007).

a) In one study of bupivacaine toxicity, rats were pretreated for 5 min with 3 mL/kg/min saline, 10% intralipid, 20% intralipid, and 30% intralipid. The dose of bupivacaine required to induce asystole was 17.7 mg/kg in the saline group, 27.6 mg/kg in the 10% intralipid group, 49.7 mg/kg in the 20% intralipid group, and 82.0 mg/kg in the 30% intralipid group. In another rat study, treatment with intralipid after bupivacaine overdose increased the LD50 of bupivacaine from 12.5 mg/kg in the saline group to 18.5 mg/kg in the intralipid group (Weinberg et al, 1998).
b) In another study, dogs received 10 mg/kg bupivacaine followed by 10 minutes of internal cardiac massage, then either normal saline or 20% lipid infusion 4 mL/kg bolus followed by 0.5 mL/kg/min for 10 minutes. All 6 lipid-treated dogs survived, compared with none of the 6 saline-treated dogs (Weinberg et al, 2003).
c) In an isolated rat heart model of bupivacaine intoxication, lipid infusion resulted in a more rapid return of spontaneous contractions and full recovery of cardiac function. In addition, lipid treatment resulted in a more rapid loss of bupivacaine from cardiac tissue, suggesting that effect is secondary to partitioning of bupivacaine into a "lipid sink" (Weinberg et al, 2006).
d) In isolated rat hearts exposed to bupivacaine, lipid application had a significant inotropic effect, increasing systolic pressure without affecting heart rate, or QRS duration (Stehr et al, 2007).

a) CASE REPORT: A 27-year-old woman presented to the ED approximately 1 hour after intentionally ingesting 7 g propranolol. She was comatose (GCS 3) with hypotension, bradycardia, and generalized tonic-clonic seizures. An ECG indicated severe sinus broad complex bradycardia. Despite supportive therapies, including administration of glucagon, insulin, and vasopressors, her hypotension and bradycardia persisted. IV lipid emulsion therapy was then initiated, 100 mL bolus of 20% intralipid followed by an infusion of 400 mL over 20 minutes. Following intralipid therapy, the patient recovered, with gradual discontinuation of vasopressor and glucagon therapy, and was referred for psychiatric care (Dean et al, 2010).
b) CASE REPORT: A 31-year-old woman presented to the ED comatose and hypotensive (80/45 mmHg), with generalized seizures, approximately 2 hours after ingesting 3.6 g propranolol and an unknown amount of ethanol. An ECG showed nonspecific intraventricular conduction delay followed by supraventricular tachycardia with wide QRS complex. Toxicological analysis of the patient's blood revealed a propranolol concentration of 4.21 mg/L and an ethanol concentration of 2.42 g/L. Despite treatment with glucagon, insulin, sodium bicarbonate, diazepam and dopamine, the patient continued to deteriorate clinically, prompting a decision to start IV lipid emulsion therapy, with a 100 mL bolus of 20% intralipid followed by an infusion of 400 mL over a 20-minute period. Following intralipid therapy, the patient's condition improved with discontinuation of seizures and an increase in blood pressure (110/50 mmHg); however, within 30 minutes after cessation of intralipid treatment, her blood pressure once again decreased to 70/30 mmHg. Intralipid therapy was restarted 60 minutes after the first dose, with an infusion of 500 mL 20% intralipid at a rate of 10 mL/min. The patient rapidly improved with a return of sinus rhythm and an increase in blood pressure to 120/60 mmHg. The patient remained stable, and was transferred to the psychiatric unit the next day (Jovic-Stosic et al, 2011).
c) ANIMAL STUDIES

a) CASE REPORT: A 32-year-old woman developed hypotension and sinus bradycardia after intentionally ingesting 475 mg of metoprolol in a suicide attempt. IV lipid emulsion (ILE) therapy was initiated with a 100 mL bolus dose followed by a 0.5 mL/kg/min infusion for 2 hours (total dose 3100 mL). The patient's blood pressure and heart rate increased 2 hours following therapy. Although her urine color was red, suspected to be due to ILE therapy, she had no signs and symptoms related to metoprolol intoxication, and she was discharged 24 hours post-admission following psychiatric consultation. Four days later, she presented to the emergency department with elevated pancreatic enzymes (amylase 249 units/L, lipase 438 units/L) leading to a diagnosis of minimal change pancreatitis, a complication related to ILE therapy (Eren Cevik et al, 2014).

a) It is suspected that IV lipid emulsion therapy may have targeted the lipophilic moiety of the caffeine molecule, contributing to the effective resolution of signs and symptoms following caffeine overdose(Schmidt et al, 2015).

a) CASE REPORT: A 71-year-old woman with a medical history of hypertension, emphysema, and depression presented 1.5 hours after ingesting 27 tablets of amlodipine 5 mg. She was alert, oriented, and in no distress, and her vital signs were: temperature 36.6 degrees C, blood pressure (BP 85/44 mm Hg), pulse (heart rate, 79 beats/min), respiratory rate (20/min). An initial laboratory result revealed hyponatremia and anemia; all other laboratory results were normal. She developed hypotension (systolic BP, 79 mmHg) 2 hours later. Despite symptomatic therapy, she remained hypotensive in the ICU, and her urine output decreased to 10 mL/hr. Her condition deteriorated and pulmonary edema was noted clinically and on chest x-ray. She was intubated and her peri-intubation arterial blood gas (ABG) revealed pH=7.17, pCO2=31, and pO2=80. Based on a written lipid emulsion therapy protocol (written protocol: Intralipid 20%: 1.5 mL/kg over 1 min; then an infusion of 0.25 mL/kg/min; max total dose, 8 mL/kg. In practice, for an adult weighing 70 kg: take a 500 mL bag of Intralipid 20% and a 50 mL syringe; draw up 50 mL and give stat IV, x 2; then attach the bag to an IV administration set (macrodrip) and run it IV over the next 25 minutes), a maximum of 387.5 mL of intralipid for a 50 kg patient was ordered and treatment was started 12.5 hours after presentation. However, she inadvertently received a total of 2000 mL of 20% intralipid which ran for 4.5 hours (greater than 5 times the maximum suggested dose). Because of severe lipemia, no metabolic panel and CBC analysis could be obtained. There were no other obvious clinical affects from the intravenous lipid overdose On hospital day 2, the treatment team felt that recovery from the amlodipine overdose was unlikely. After her family decided to withdraw care, she died within the next 24 hours (West et al, 2010).

a) CASE REPORT: A 57-year-old woman presented to the emergency department with hypotension and bradycardia after a multi-drug overdose ingestion, including an unknown amount of sustained release diltiazem 360 mg. An initial ECG showed sinus bradycardia without evidence of other ECG abnormalities, including AV block , wide QRS, or prolonged QT. The patient was given calcium chloride, glucagon, and vasopressors for persistent hypotension; however, 9 hours later, the patient developed chest pain with ECG changes. Her mean arterial pressure (MAP) was 60 mmHg. Intravenous lipid therapy 20% was initiated with a loading dose of 1.5 mg/kg, followed by an infusion of 0.25 mL/kg/min for a total dose of 8 mL/kg. Following completion of therapy, the patient's MAP increased to 68 mmHg, and vasopressor therapy was discontinued within 45 hours. The patient made a complete recovery and was discharged approximately 16 days post-ingestion (Wilson et al, 2012).
b) CASE REPORT: An 18-year-old woman presented with hypotension (71/40 mmHg) and tachycardia (102 bpm) approximately 8 hours after ingesting 3600 mg of sustained release diltiazem. Despite administration of fluids, and calcium chloride, the patient's hypotension persisted and she became oliguric. Four hours post-admission, she developed respiratory failure, necessitating intubation and mechanical ventilation. The patient was also receiving high-dose norepinephrine (6.66 mcg/kg/min), resulting in slight increases in her systolic and mean arterial blood pressures. Hyperinsulinemic euglycemia therapy was started with no significant improvement in her hemodynamic status and, 3 hours later, intravenous lipid emulsion (ILE) 20% was initiated with a bolus dose of 1.5 mL/kg, followed by a continuous infusion of 0.25 mL/kg over 1 hour. Following ILE therapy, the patient's hemodynamic status improved, with discontinuation of norepinephrine on hospital day 4. The patient made a complete recovery and was discharged approximately 9 days post-ingestion (Montiel et al, 2011).
c) CASE REPORT: A 53-year-old man developed bradycardia and hypotension (HR 30 beats/min; mean arterial pressure 40 mmHg) after ingesting diltiazem 3600 mg and propranolol 1200 mg. Despite treatment with calcium salts, catecholamines, high-dose insulin, bicarbonate, and atropine, his condition did not improve. Within 1 minute of receiving 150 mL of 20% IFE he developed brady-asystolic arrest, but his pulse returned to normal after 6 minutes of CPR. Despite aggressive supportive care, his condition deteriorated and he died of multisystem organ failure on day 7. Although the exact cause of arrest in this patient is uncertain, several possible causes were suggested: IFE interaction with other resuscitation drugs, a sudden increase in absorption of drug in the GI tract, a brief lack of oxygen in the lipid-laden blood circulating in the coronary vessels contributing to the arrests, fatal ingestions of drugs regardless of therapy (Cole et al, 2014).

a) CASE REPORT: A 32-year-old man intentionally ingested large quantities of multiple medications, one of which was 13.44 g of verapamil. He was found 12 hours later to be poorly responsive with incoherent speech and hypotensive (69/26 mmHg) with a pulse of 55 beats/min. Fluids, pressors, calcium and glucagon were all administered, but he remained hypotensive, with junctional bradycardia, metabolic acidosis and renal insufficiency. Then, upon transfer, 100 mL of 20% lipids was infused followed by a 0.5 mL/kg/hr infusion for 24 hours. The patient's clinical parameters improved within an hour of lipid therapy initiation, and he made a full recovery (Young et al, 2009).
b) CASE REPORT: A 39-year-old woman presented to the emergency department with dyspnea, chest tightness, lethargy, diaphoresis, and hypotension (76/41 mmHg) after intentionally ingesting 17 240-mg tablets of extended release verapamil (total dose ingested 4.08 g). Despite treatment with IV fluids and norepinephrine therapy, the patient's hypotension persisted. Approximately 17 hours post-presentation, the patient was switched to dopamine, without effect, and, approximately 15 hours later, the patient was given 100 mL of 20% lipids, administered intravenously over 20 minutes, followed by a continuous infusion of 0.5 mL/kg/hour for the next 8 hours. During this time period, the patient's blood pressure improved and dopamine therapy was gradually discontinued (Franxman et al, 2011).

a) In one study, rats received a verapamil infusion at 37.5 mg/kg/hr; 5 minutes after the start of the infusion' they received 12.4 mL/kg of either 20% lipid or normal saline, and the verapamil infusion was continued until the animals died. Lipid-treated animals had prolonged survival (44 +/- 21 minutes vs 24 +/- 9 minutes in saline-treated animals) and they had a higher median lethal dose (25.7 mg/kg (95% confidence interval 24.7 to 26.7 mg/kg) compared with 13.6 mg/kg (95% confidence interval 12.2 to 15.0 mg/kg) in saline-treated animals) (Tebbutt et al, 2006).
b) In a dog study, severe verapamil toxicity was induced (50% decrease in mean arterial pressure), then animals were treated with atropine and calcium chloride, and randomized to 7 mg/kg of either 20% lipid emulsion or normal saline. The lipid-treated animals had increased mean arterial pressures compared with saline-treated animals. In addition 100% of the lipid-treated animals survived compared with 14% of the saline-treated animals (Bania et al, 2007).
c) In a rat study, the greatest benefit of survival occurred with 18.6 mL/kg intravenous fat emulsion therapy in verapamil poisoning (Perez et al, 2008).

a) Rabbits received 30 mg/kg of chlorpromazine after pretreatment with either 15 mL of a lipid emulsion or 15 mL xylitol; all lipid-treated rabbits survived compared with none of the xylitol-treated animals. This difference was not observed when a chlorpromazine dose of 15 mg/kg was used (Krieglstein et al, 1974).

a) In a rabbit study, a single bolus of cyclosporine 10 mg/kg was administered; in half the animals the cyclosporin was mixed with 3 mL of lipid emulsion. In the animals who received the cyclosporine mixed with lipid emulsion, cyclosporine elimination half-life was shorter (191 +/- 25 min vs 298 +/- 59 min in controls), and total body clearance and volume of distribution were reduced by 65% to 70% (Shah & Sawchuk, 1991).

a) CASE REPORT: A 25-year-old woman, who ingested an unknown amount of amitriptyline, developed hypotension, a wide QRS (186 ms), QTc interval prolongation, and episodic pulseless wide-complex tachycardia that recurred despite electrical cardioversion and treatment with lidocaine, magnesium sulfate, and sodium bicarbonate. The patient was then given 150 mL IV bolus of 20% lipids, followed by a continuous infusion at 16 mL/hour over the next 36 hours (receiving a total of 814 mL of 20% lipid (16.3 mL/kg)). During lipid treatment, the patient did not experience any more episodes of wide-complex tachycardia. However, within hours after discontinuing the lipid infusion, the QRS duration widened, the QTc interval continued to be prolonged, and the patient again developed pulseless wide-complex tachycardia twice, requiring electrical cardioversion each time. Following the second cardioversion, the tachycardia resolved, although the patient continued to have a prolonged QRS duration and QTc interval requiring intermittent sodium bicarbonate administration until 8 days post-admission (Kiberd & Minor, 2012).
b) CASE REPORT: A 27-year-old man presented with a severe overdose of amitriptyline 4.25 g. He presented with a GSC of 3, HR 116, BP 67/40 mmHg, respiratory rate 8 per minute and temperature was 35.4 degrees Celsius. He developed two tonic-clonic seizures and pulseless ventricular tachycardia treated with CPR and IV epinephrine and sodium bicarbonate. Return of spontaneous circulation (ROSC) occurred after 18 minutes but a second episode of pulseless VT arrest occurred 2 minutes later and ROSC was after 4 min of CPR. The patient was transferred to the ICU and was still critical 4 hours after presentation. Prior to administration of IFE, the patient's vasopressor dosage was norepinephrine 70 mcg/min and epinephrine 20 mcg/min with a plasma lactate level of 9.7 mmol/L. He was administered 100 mL of 20% intralipid and followed by an infusion of 400 mL over 30 minutes. Within 30 minutes to one hour after the completion of the IV lipid emulsion, the patient's vasopressor needs rapidly declined and he was eventually weaned off approximately 13 hours after presentation and was extubated the next day (Engels & Davidow, 2010).
c) CASE REPORT: A 13-year-old girl developed a delayed-onset generalized tonic-clonic seizure and pulseless wide-complex dysrhythmias approximately 19 hours after ingesting an unknown amount of 150-mg amitriptyline tablets. Despite aggressive resuscitative efforts, the patient's rhythm degenerated to torsades de pointes. Approximately 30 minutes after initiation of resuscitation, 20% IV lipid emulsion therapy was started. The patient initially received 2 IV boluses of 1.5 mg/kg each, administered over a 3-minute period, with each bolus administered 5 minutes apart, followed by a continuous infusion of 0.25 mg/kg/minute for 30 minutes. Following administration of the second bolus, the patient's cardiac status improved with termination of her dysrhythmias. She also developed pancreatitis after receiving lipid emulsion. She recovered following supportive care (Levine et al, 2012).

a) A 36-year-old woman presented to the emergency department comatose (Glasgow Coma Scale score of 4), hypotensive, and tachycardic, approximately 90 minutes after ingesting 2.25 g of dothiepin. An ECG revealed a broad-complex tachycardia with a prolonged QTc interval of 502 ms. Approximately 30 minutes post-presentation, the patient developed cardiac arrest, that was successfully electrically cardioverted, although the patient continued to have broad complex tachycardia, despite administration of IV amiodarone, sodium bicarbonate boluses, and overdrive-pacing. A 100 mL bolus of 20% IV lipid emulsion was then administered over 1 minute, followed by a 400 mL infusion administered over a 15-minute period. During administration, sinus rhythm was restored and remained stable. Although the patient's clinical course was complicated with development of ventilator-associated pneumonia, she recovered with supportive care and was discharged with a repeat ECG demonstrating sinus rhythm with partial right bundle branch block and normal QRS and QTc durations (Blaber et al, 2012).

a) In one study, rabbits received clomipramine 320 mg/kg/hr until mean arterial pressure was 50% of baseline, then were treated either with 12 mL/kg normal saline, or 3 mL/kg 8.4% sodium bicarbonate, or 12 mL/kg 20% lipid emulsion. Lipid therapy reversed hypotension more effectively than saline or bicarbonate. In addition, all bicarbonate-treated rabbits developed pulseless electrical activity refractory to resuscitation by 10 minutes, while spontaneous circulation was maintained in all lipid-treated animals (Harvey & Cave, 2007).
b) In another study, rats received clomipramine 12.5 mg dissolved in either normal saline or 10% lipid (total volume 2.5 ml). All animals in the saline group died, while 3 of 15 (20%) of the lipid group died (Yoav et al, 2002).
c) In another rat study, pretreatment with lipid emulsion did not increase mean arterial pressure or prolong survival in amitriptyline-poisoned animals (Bania & Chu, 2006).

a) CASE REPORT: An adult was admitted comatose approximately 3.5 hours after intentionally ingesting 4.3 g of quetiapine and 3.1 g of sertraline. Initially, the patient was hypotensive (88/64 mmHg) and in normal sinus rhythm (heart rate 80 beats per minute) with spontaneous respirations. Glasgow Coma Score (GCS) was 3 on admission. Based on his clinical symptoms and the lipophilic nature of the ingested drugs, the patient was started on a 20% lipid emulsion at an initial bolus dose of 1.5 mL/kg (100 mL), which was followed by an infusion of 6 mL/kg (400 mL) over the next hour. The patient rapidly regained consciousness within 15 minutes and was able to protect his airway. The patient continued to neurologically improve and remained hemodynamically stable. Quetiapine and sertraline serum concentrations could not be obtained; a benzodiazepine level was negative. Nineteen hours after exposure the patient had a GCS of 12, and was transferred a few hours later to a psychiatric care setting with a GCS of 15 (Finn et al, 2009).

a) CASE REPORT: A 17-year-old girl ingested bupropion (estimated 7.95 g) and lamotrigine (estimated 4 g). She presented comatose and tachycardic with a prolonged QRS (122 msec) and a prolonged QTc (485 msec). She had a seizure about 10 hours after presentation followed by cardiovascular collapse with a pulseless, wide complex rhythm. Advanced cardiac life support (ACLS) was commenced, and she developed pulseless ventricular tachycardia and ventricular fibrillation. She was intubated, received epinephrine (6 mg), amiodarone (300 mg), magnesium (1 g), 11 defibrillations, without return of circulation. After a 50 mEq bolus of sodium bicarbonate, she regained a pulse, with a wide complex rhythm (QRS 152 msec) and hypotension (84/55 mmHg). Pulseless electrical activity recurred after 17 minutes and ACLS resumed. Transcutaneous pacing was unsuccessful, she received another 12 mg epinephrine, 2 boluses of 50 mEq bicarbonate, 1 g calcium chloride, high dose norepinephrine and epinephrine infusions without sustained spontaneous circulation. A 100 mL bolus of 20% lipid emulsion was administered 52 minutes after the second period of ACLS was started. One minute later she had a sustained palpable pulse, and during the next 15 minutes the wide QRS narrowed and sinus rhythm returned. She received another 100 mEq sodium bicarbonate. She had another period of pulseless ventricular tachycardia 90 minutes later, which resolved after 1 mg epinephrine and one minute of chest compressions. Pressors and amiodarone were weaned over the next 2 days. She developed acute lung injury and mild hypoxic brain injury, but on discharge was talkative, with a slight tremor, mild memory deficits and fine motor incoordination. Serum bupropion concentrations were highest 77 minutes after the lipid emulsion infusion and then declined in parallel with the serum triglyceride concentration. This was not true of the serum lamotrigine concentration(Sirianni et al, 2008).

a) CASE REPORT: A 72-year-old woman presented to the hospital after ingesting approximately 1500 mg flecainide, 150 mg of oxazepam and 150 mcg of levothyroxine in a suicide attempt. Upon arrival, the patient had mild bradycardia (55 bpm), hypotension (70/50 mmHg), and tachypnea (30 breaths/min). ECG revealed a widening of the QRS complex longer than 0.2 sec and prolongation of the QT interval. The patient was refractory to aggressive supportive care (including ventilation and vasopressors) and was started on intravenous lipid emulsion at 1.5 ml/kg bolus, followed by an infusion of 0.25 mg/min. The patient's clinical presentation improved within 30 minutes of lipid emulsion. The patient was transferred to an intensive care unit and eventually recovered without long term medical deficit (Moussot et al, 2011).

a) CASE REPORT: An 18-year-old woman with a history of epilepsy presented with agitation, disorientation and noncooperative with a Glasgow Coma Scale (GCS) score of 12 about an hour after ingesting an unknown amount of lamotrigine 100 mg tablets and sertraline 50 mg tablets. Physical examination revealed vertical nystagmus and myoclonia. She responded to questions with dysphasia within an hour of receiving IV lipid emulsion therapy (bolus of 100 mL and 0.5 mL/kg/min infusion for 2 hours; total dose, 3100 mL). She had a GCS score of 15 and mild dysarthria 6 hours later (Eren Cevik et al, 2014).

a) CASE REPORT: Administration of intravenous fat emulsion (IFE) combined with high-dose insulin was successfully used in a 48-year-old man who developed cardiac arrest following a suspected ingestion of nebivolol (300 mg), baclofen, and diazepam, as well as cocaine use. On presentation to the ED (approximately 3 hours postingestion), the patient was unresponsive with a Glasgow Coma score of 3, blood pressure of 92/52 mmHg, and a heart rate of 72 bpm. Approximately 5 hours later, the patient's heart rate decreased to 35 bpm, his systolic blood pressure decreased to 50 mmHg, and he developed bradyasystolic cardiac arrest. Resuscitative measures included CPR, 2 boluses each of atropine 1 mg and epinephrine 1 mg, administered 4 minutes apart, and 100 mL bolus of 20% IFE. Approximately 1 minute later, the patient's heart rate and blood pressure increased to 123 bpm and 251/162 mmHg, respectively, however bradycardia and hypotension recurred within 20 minutes, necessitating initiation of a 20% IFE infusion of 0.25 mL/kg/min continued over an hour, along with administration of an IV bolus of 100 units regular insulin, followed by a high-dose insulin infusion (up to 21.8 units/kg/hour). Supportive care included calcium (117 mEq) and dextrose (485 g) in order to maintain euglycemia. Over the next several days, the patient's hemodynamic status gradually normalized, and he was discharged on hospital day 11 without neurologic sequelae (Stellpflug et al, 2010).

a) CASE REPORT: A 44-year-old woman ingested diazepam 200 mg, lamotrigine 20 g, and venlafaxine 4.5 g, and was found unconscious at home. After admission, a tonic-clonic seizure, rigidity, hyperreflexia, and reflex myocloni were observed. Laboratory results revealed sodium level of 129 mmol/L, creatinine kinase of 1915 Units/L, and creatine kinase-MB of 31 Units/L. Despite supportive therapy, including 8 hours of hemodialysis, her rigidity and hyperreflexia did not improve. Following treatment with an intravenous bolus (150 mL, 2.5 mL/kg) of 20% lipid emulsion, all symptoms resolved completely. On day 6, she was transferred to a psychiatric ward. Before hemodialysis, plasma concentrations of lamotrigine, diazepam, and venlafaxine were 42.4 mg/L (therapeutic range: 1 to 4 mg/L), 560 mcg/L (therapeutic range: 200 to 500 mcg/L), and 1254 mcg/L (therapeutic range: 30 to 150 mcg/L), respectively (Dagtekin et al, 2011).

1) Initial intravenous bolus of 1.5 mL/kg 20% lipid emulsion (eg, Intralipid) over 2 to 3 minutes. Asystolic patients or patients with pulseless electrical activity may have a repeat dose, if there is no response to the initial bolus.
2) Follow with an intravenous infusion of 0.25 mL/kg/min of 20% lipid emulsion (eg, Intralipid). Evaluate the patient's response after 3 minutes at this infusion rate. The infusion rate may be decreased to 0.025 mL/kg/min (ie, 1/10 the initial rate) in patients with a significant response. This recommendation has been proposed because of possible adverse effects from very high cumulative rates of lipid infusion. Monitor blood pressure, heart rate, and other hemodynamic parameters every 15 minutes during the infusion.
3) If there is an initial response to the bolus followed by the re-emergence of hemodynamic instability during the lowest-dose infusion, the infusion rate may be increased back to 0.25 mL/kg/min or, in severe cases, the bolus could be repeated. A maximum dose of 10 mL/kg has been recommended by some sources.
4) Where possible, LRT should be terminated after 1 hour or less, if the patient's clinical status permits. In cases where the patient's stability is dependent on continued lipid infusion, longer treatment may be appropriate.

1) Initial intravenous bolus of 1.5 mL/kg 20% lipid emulsion (eg, Intralipid) over 2 to 3 minutes. Asystolic patients or patients with pulseless electrical activity may have a repeat dose, if there is no response to the initial bolus.
2) Follow with an intravenous infusion of 0.25 mL/kg/min of 20% lipid emulsion (eg, Intralipid). Evaluate the patient's response after 3 minutes at this infusion rate. The infusion rate may be decreased to 0.025 mL/kg/min (ie, 1/10 the initial rate) in patients with a significant response. This recommendation has been proposed because of possible adverse effects from very high cumulative rates of lipid infusion. Monitor blood pressure, heart rate, and other hemodynamic parameters every 15 minutes during the infusion.
3) If there is an initial response to the bolus followed by the re-emergence of hemodynamic instability during the lowest-dose infusion, the infusion rate may be increased back to 0.25 mL/kg/min or, in severe cases, the bolus could be repeated. A maximum dose of 10 mL/kg has been recommended by some sources.
4) Where possible, LRT should be terminated after 1 hour or less, if the patient's clinical status permits. In cases where the patient's stability is dependent on continued lipid infusion, longer treatment may be appropriate.