High-dose insulin: A consecutive case series in toxin-induced cardiogenic shock

Holger, Joel S.; Stellpflug, Samuel J.; Cole, Jon B.; Harris, Carson R.; Engebretsen, Kristin M.

doi:10.3109/15563650.2011.593522

Cited by 82 publications

(66 citation statements)

References 15 publications

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“…In patients with β-blocker or calcium channel-blocker poisoning, very high doses of insulin (0.5-10 U/kg/ h) have been used successfully to stimulate cardiac contractility [164,169,170]. First experiments in endotoxemic pigs with such high insulin dosages are also promising [171].…”

Section: Metabolic Interventionsmentioning

confidence: 99%

The Heart in Sepsis: From Basic Mechanisms to Clinical Management

Rudiger¹,

Singer²

2013

Current Vascular Pharmacology

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Septic shock is characterized by circulatory compromise, microcirculatory alterations and mitochondrial damage, which all reduce cellular energy production. In order to reduce the risk of major cell death and a diminished likelihood of recovery, adaptive changes appear to be activated. As a result, cells and organs may survive in a non-functioning hibernation-like condition. Sepsis-induced cardiac dysfunction may represent an example of such functional shutdown. Sepsis-induced myocardial dysfunction is common, corresponds to the severity of sepsis, and is reversible in survivors. Its mechanisms include the attenuation of the adrenergic response at the cardiomyocyte level, alterations of intracellular calcium trafficking and blunted calcium sensitivity of contractile proteins. All these changes are mediated by cytokines. Treatment includes preload optimization with sufficient fluids. However, excessive volume loading is harmful. The first line vasopressor recommended at present is norepinephrine, while vasopressin can be started as a salvage therapy for those not responding to catecholamines. During early sepsis, cardiac output can be increased by dobutamine. While early administration of catecholamines might be necessary to restore adequate organ perfusion, prolonged administration might be harmful. Novel therapies for sepsis-induced cardiac dysfunction are discussed in this article. Cardiac inotropy can be increased by levosimendan, istaroxime or omecamtiv mecarbil without greatly increasing cellular oxygen demands. Heart rate reduction with ivabradine reduces myocardial oxygen expenditure and ameliorates diastolic filling. Beta-blockers additionally reduce local and systemic inflammation. Advances may also come from metabolic interventions such as pyruvate, succinate or high dose insulin substitutions. All these potentially advantageous concepts require rigorous testing before implementation in routine clinical practice. While early administration of catecholamines might be necessary to restore adequate organ perfusion and pressure, prolonged administration might be harmful.Novel therapies for sepsis-induced cardiac dysfunction are discussed in this article. Cardiac inotropy can be increased by levosimendan, istaroxime or omecamtiv mecarbil without greatly increasing cellular oxygen demands. Heart rate reduction with ivabradine will reduce myocardial oxygen expenditure and ameliorate diastolic filling. Beta-blockers additionally reduce local and systemic inflammation. Advances may also come from metabolic interventions such as pyruvate, succinate or high dose insulin substitutions. However, all these potentially advantageous concepts require rigorous testing before implementation in routine clinical practice.-3 -Alain Rudiger & Mervyn Singer: The heart in sepsis

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Section: Metabolic Interventionsmentioning

confidence: 99%

The Heart in Sepsis: From Basic Mechanisms to Clinical Management

Rudiger¹,

Singer²

2013

Current Vascular Pharmacology

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“…7,8 However, daily administration of insulin by injection is uncomfortable for patients and can even be dangerous: the injection of excess insulin can result in serious shock responses such as hypoglycemia, syncope, or even death. 9,10 To ameliorate these issues, much effort has been invested in the development of smart drug delivery systems that are able to release insulin in response to changes in the blood glucose level. A significant number of reports of glucose-sensitive systems have emerged in the literature over the last decade or so.…”

Section: Introductionmentioning

confidence: 99%

Glucose- and temperature-sensitive nanoparticles for insulin delivery

Wu¹,

Williams²,

Li³

et al. 2017

IJN

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Glucose- and temperature-sensitive polymers of a phenylboronic acid derivative and diethylene glycol dimethacrylate (poly(3-acrylamidophenyl boronic acid- b -diethylene glycol methyl ether methacrylate); p(AAPBA- b -DEGMA)) were prepared by reversible addition–fragmentation chain transfer polymerization. Successful polymerization was evidenced by 1 H nuclear magnetic resonance and infrared spectroscopy, and the polymers were further explored in terms of their glass transition temperatures and by gel permeation chromatography (GPC). The materials were found to be temperature sensitive, with lower critical solution temperatures in the region of 12°C–47°C depending on the monomer ratio used for reaction. The polymers could be self-assembled into nanoparticles (NPs), and the zeta potential and size of these particles were determined as a function of temperature and glucose concentration. Subsequently, the optimum NP formulation was loaded with insulin, and the drug release was studied. We found that insulin was easily encapsulated into the p(AAPBA- b -DEGMA) NPs, with a loading capacity of ~15% and encapsulation efficiency of ~70%. Insulin release could be regulated by changes in temperature and glucose concentration. Furthermore, the NPs were non-toxic both in vitro and in vivo. Finally, the efficacy of the formulations at managing blood glucose levels in a murine hyperglycemic diabetes model was studied. The insulin-loaded NPs could reduce blood glucose levels over an extended period of 48 h. Since they are both temperature and glucose sensitive and offer a sustained-release profile, these systems may comprise potent new formulations for insulin delivery.

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“…The only poor outcome in this series resulted from a failure to comply with the agreed management protocol involving insulin. 10 The exact dose of insulin required can be titrated; doses up to 10 U/kg/hr are well described as efficacious and safe.…”

Section: Insulin and Dextrosementioning

confidence: 99%

Poisoning and self-harm

Bateman¹

2012

Clinical Medicine

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High-dose insulin: A consecutive case series in toxin-induced cardiogenic shock

Cited by 82 publications

References 15 publications

The Heart in Sepsis: From Basic Mechanisms to Clinical Management

The Heart in Sepsis: From Basic Mechanisms to Clinical Management

Glucose- and temperature-sensitive nanoparticles for insulin delivery

Poisoning and self-harm

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