The Spectrum of Amniotic Fluid Embolism: Is Intralipid the solution ?

By Joseph Eldor

In 1998 it was first showed that intravenous Intralipid could prevent or improve resuscitation from cardiovascular collapse by severe bupivacaine overdose in rats. Since then published examples now include toxicities related to verapamil, diltiazem, amlodipine, quetiapine and sertraline, haldoperidol, lamotrigine, olanzapine, propranolol, atenolol, nevibolol, doxepin, dosulepin, imipramine, amitriptyline, glyosphate herbicide, flecainide, venlafaxine, moxidectin, and others. Amniotic fluid embolism (AFE) is a rare but potentially catastrophic obstetric emergency. Despite earlier recognition and aggressive treatment, morbidity and mortality rates remain high. An estimated 5% - 15% of all maternal deaths in Western countries are due to AFE. The pathophysiology of AFE is not completely understood. AFE most commonly occurs during labor, delivery, or the immediate postpartum period. However, it has been reported to occur up to 48 h postpartum. Pulmonary hypertension and right heart strain/failure may be the result of physical amniotic fluid debris in the pulmonary vasculature or, perhaps more likely, result from circulating pulmonary vasoconstrictive mediators. Therapy with Intralipid in male rats resulted in 100% survival and prevented Pulmonary arterial hypertension-induced right ventricular failure by preserving right ventricular pressure and right ventricular ejection fraction and preventing right ventricular hypertrophy and lung remodeling. In preexisting severe Pulmonary arterial hypertension, Intralipid attenuated most lung and right ventricular abnormalities. The beneficial effects of Intralipid in Pulmonary arterial hypertension seem to result from the interplay of various factors, among which preservation and/or stimulation of angiogenesis, suppression and/or reversal of inflammation, fibrosis and hypertrophy, in both lung and right ventricular, appear to be major contributors. In conclusion, Intralipid not only prevents the development of Pulmonary arterial hypertension and right ventricular failure but also rescues preexisting severe Pulmonary arterial hypertension. Intralipid treatment is a new treatment for AFE (amniotic fluid embolism).

• Language: English
• Publisher: Joseph Eldor
• Release date: Jan 1, 2018
• ISBN: 9781370130016

Book preview

1. Is INTRALIPID the solution?

In 1998 it was first showed that intravenous Intralipid could prevent or improve resuscitation from cardiovascular collapse by severe bupivacaine overdose in rats. Since then published examples now include toxicities related to verapamil, diltiazem, amlodipine, quetiapine and sertraline, haldoperidol, lamotrigine, olanzapine, propranolol, atenolol, nevibolol, doxepin, dosulepin, imipramine, amitriptyline, glyosphate herbicide, flecainide, venlafaxine, moxidectin, and others. Amniotic fluid embolism (AFE) is a rare but potentially catastrophic obstetric emergency. Despite earlier recognition and aggressive treatment, morbidity and mortality rates remain high. An estimated 5% - 15% of all maternal deaths in Western countries are due to AFE. The pathophysiology of AFE is not completely understood. AFE most commonly occurs during labor, delivery, or the immediate postpartum period. However, it has been reported to occur up to 48 h postpartum. Pulmonary hypertension and right heart strain/failure may be the result of physical amniotic fluid debris in the pulmonary vasculature or, perhaps more likely, result from circulating pulmonary vasoconstrictive mediators. Therapy with Intralipid in male rats resulted in 100% survival and prevented Pulmonary arterial hypertension-induced right ventricular failure by preserving right ventricular pressure and right ventricular ejection fraction and preventing right ventricular hypertrophy and lung remodeling. In preexisting severe Pulmonary arterial hypertension, Intralipid attenuated most lung and right ventricular abnormalities. The beneficial effects of Intralipid in Pulmonary arterial hypertension seem to result from the interplay of various factors, among which preservation and/or stimulation of angiogenesis, suppression and/or reversal of inflammation, fibrosis and hypertrophy, in both lung and right ventricular, appear to be major contributors. In conclusion, Intralipid not only prevents the development of Pulmonary arterial hypertension and right ventricular failure but also rescues preexisting severe Pulmonary arterial hypertension. Intralipid treatment is a new treatment for AFE (amniotic fluid embolism) which was never suggested before (1).

Its first clinical use was done in Texas A&M University System Health Science Center College of Medicine, Baylor Scott & White Health, Temple, Texas on a 28-year-old otherwise healthy, nonsmoking, 76-kg primigravid woman presented at 41 weeks of gestation for vaginal misoprostol induction of labor (2).

Despite several administrations of ACLS medications including vasopressin, sodium bicarbonate, calcium chloride, atropine, and a total of 6 mg epinephrine, the patient’s heart rhythm fluctuated between profound bradycardia and asystole for a prolonged period of 40 minutes.

As a last resort, IV lipid 20% emulsion (1.5mL/kg) was administered as a bolus. Within 30 to 90 seconds, the patient had return of spontaneous circulation, normal sinus rhythm, and dramatic improvement in left and right ventricular function, shown clearly by TEE. After several minutes, the patient’s condition slowly deteriorated once again to asystole, at which time CPR was once again started and a second lipid emulsion bolus (1.5mL/kg) was administered and followed with an infusion at 0.25mL/kg/min. Within 30 to 60 seconds, the patient again had a return of spontaneous circulation with normal sinus rhythm. In addition, she also exhibited spontaneous movements of her extremities.

Although Eldor and Kotlovker (13) were the first to suggest a possible benefit of lipid emulsion therapy in the treatment of AFE, this is the first published instance in which a patient received intravenous lipid emulsion temporally related to the recovery from cardiovascular collapse associated with amniotic fluid embolism. The main limitation is the fact that AFE is a diagnosis of exclusion; however, other differential diagnoses are less likely. There is TEE evidence that shows overall improvement of cardiac function temporally related to administration of lipid emulsion. The patient had return of spontaneous circulation occurring shortly after the administration of lipid emulsion on 2 different occasions after exhausting all other ACLS options, suggesting that lipid emulsion may have been responsible for the successful resuscitation. In addition, after the initial improvement, a relapse occurred, which was treated with a second bolus of lipid emulsion after which the same improvement in clinical and cardiac function occurred. Full neurologic recovery was noted after significantly prolonged cardiovascular collapse with chest compressions (40 minutes) and exhaustion of other standard ACLS medications. The excellent neurologic recovery emphasizes the importance of high quality and sustained CPR. Furthermore, a possible physiologic mechanism for the cardiopulmonary recovery is presented and is based on scientific models from previous research on the effects of lipid emulsion and its components. This report suggests a possible benefit of lipid emulsion therapy in the treatment of cardiovascular collapse caused by AFE, and further research will be required to elucidate the role of lipid emulsion therapy in the setting of AFE.

References

1. Joseph Eldor, Vladimir Kotlovker. Intralipid for Amniotic Fluid Embolism (AFEJ. Open Journal of Anesthesiology Vol.2 No.4(2012), https://file.scirp.org/Html/7-1920052_22244.htm

2. Windrik Lynch, MD, Russell K. McAllister, MD, Jack F. Lay Jr, MBA, MD, and William C. Culp Jr, MD. Lipid Emulsion Rescue of Amniotic Fluid Embolism Induced Cardiac Arrest: A Case Report. A&A Case Reports. 2017;8:64-66.

http://www.csen.com/AFE.pdf

2. The Intralipid Sink Effect

Papadopoulou A et al. (1) hypothesized that by substituting a dye surrogate in place of local anesthetic, they could visually demonstrate dye sequestration by lipid emulsion that would be dependent on both dye lipophilicity and the amount of lipid emulsion used.

They selected 2 lipophilic dyes, acid blue 25 and Victoria blue, with log P values comparable to lidocaine and bupivacaine, respectively. Each dye solution was mixed with combinations of lipid emulsion and water to emulate lipid rescue treatment at dye concentrations equivalent to fatal, cardiotoxic, and neurotoxic local anesthetic plasma concentrations. The lipid emulsion volumes added to each dye solution emulated equivalent intravenous doses of 100, 500, and 900 mL of 20% Intralipid in a