Search Results (48)

Coagulation testing is commonly used in the intensive care unit (ICU) to monitor and manage the hemostatic balance, assess bleeding risk, and guide anticoagulant therapy. Routine tests used for this purpose include prothrombin time, activated partial thromboplastin time, fibrinogen, and anti-Xa assays. Some of the drugs commonly used in critically ill patients may influence coagulation assays by interacting in vitro with reagents or in vivo with coagulation pathways, thus altering the coagulation cascade and the fibrinolytic pathway. While the pharmacological effects of drugs on coagulation are usually documented, to our knowledge, no comprehensive review article has been published to date. In this review, we have conducted a critical analysis of the literature to define: (1) the impact of hydroxocobalamin, intravenous lipid emulsion, and propofol on chromogenic assays; (2) the impact of PEGylated compounds, emicizumab, recombinant activated factor VII, antibiotics, and sugammadex on chronometric assays; (3) the challenges associated with bridging anticoagulation in the ICU as well as the effect of N-acetylcystein, serotonin reuptake inhibitors, and tramadol on the hemostasis system. For each drug, we specify the routine coagulation assay that is impacted, whether this is linked to an in vitro interference or an in vivo effect, and the potential consequences on patient management. Full article

Introduction: Sedative and antipsychotic (SAP) agents are amongst the most common overdoses seen clinically, with few available antidotes. The proposed “lipid shuttle” mechanism of action for intravenous lipid emulsion (ILE) could augment the redistribution of SAP agents from the central nervous system in overdoses. We reviewed randomised controlled clinical trials to evaluate the effect of intravenous lipid emulsion when the indication for use was a reduction in the level of consciousness in SAP overdoses. Methods: We searched for human randomized controlled trials comparing the use of ILE to placebos in SAP drug overdoses. Animal and non-randomised human studies were excluded. Relevant databases were searched with two independent reviewers assessing studies for inclusion and risk of bias using the ROB 2 tool. Results: Five identified studies enrolled 270 patients in total, of whom 226 had isolated tramadol or clozapine toxicity. One study was assessed as having serious concerns for bias, and the other four as having some potential for bias. In all studies, there was a statistically significant increase in the Glasgow Coma Scale (GCS), favouring the ILE groups. This effect does not appear to have been due to changes in haemodynamics. Secondary outcomes on length of stay and QT interval were also positive. No patient died in any study. Conclusions: In the five reported randomised human trials of the effect of ILE on level of consciousness post-SAP overdose, patients receiving ILE had a greater increase in GCS over time. The potential for bias existed in all studies, and trial results may be true but specific to the intoxicants and situations studied, which prevents the generalisability of findings. More research is both feasible and necessary in this area. Full article

Malnutrition in critically ill patients represents a major concern as it can lead to adverse outcomes including increased morbidity and mortality. These patients exhibit an impaired immune response accompanied by increased oxidative stress. Nutritional support, including parenteral nutrition (PN), is critical in these patients. Intravenous lipid emulsions (ILEs), a key component of PN, provide energy and intervene in the modulation of inflammation. This was a secondary study of a randomized clinical trial at the Reina Sofia University Hospital (Murcia, Spain) for critically ill patients following major abdominal surgery that were administered PN supplemented with olive-oil-based ILE (OO-ILE, n = 29) or a mixed-lipid ILE (soybean oil, medium chain triglycerides, OO and fish oil, SMOF-ILE, n = 25). The effects on clinical outcomes, metabolic markers, oxidative stress, and inflammation were evaluated. No significant differences were observed between groups in the clinical parameters and outcomes, oxidative stress, or inflammatory markers. The within-group evaluation demonstrated an increase in total antioxidant capacity in both groups, while OO-ILE increased the levels of 15-F2t-isoprostane. In addition, the results showed that both mixtures reduced the release of IL-1β and IL-6. These findings suggest that both treatments had similar effects on oxidative stress and inflammatory response in this type of patient. Full article

Vinpocetine (VP) is distributed after oral and intravenous administration, and its uptake in the thalamus, basal ganglia, and visual cortex. Due to poor bioavailability (~7%) and marked first-pass effect (~75%), including a short half-life (2–3 h), oral administration of VP is limited. It requires frequent administration of the drug to obtain a therapeutic effect. Attempts to overcome these difficulties include the use of new drug delivery systems and/or alternative routes of drug administration. One possibility is the common administration of lipid emulsion and drug using the same catheter. However, this procedure is not recommended due to potential interaction and lack of safety data. For this purpose, we checked the compatibility of VP solutions with eight commercially available parenteral nutrition admixtures, i.e., Lipoflex special, Omegaflex special, Lipoflex peri, Omegaflex peri, Kabiven, SmofKabiven, Kabiven Peripheral, and Olimel Peri N4E. Coadministration is only possible if the stability of the drug and the lipid emulsion is confirmed. The available data are scarce and only concern the incompatibility of VP with ibuprofen. Compatibility tests were carried out in simulated administration through a Y-site connector using clinical flow rates. The stability of the drug and lipid emulsion was assessed by visual inspection and measurement of pH, osmolality, particle size as mean droplet diameter (MDD) and percentage of lipids residing in globules larger than 5 µm (PFAT5), zeta potential, polydispersity index, and lipid-free parenteral nutrition admixture(PNA) turbidity. The results of the compatibility of VP with eight commercial PN admixtures showed that all lipid emulsions show different signs of destabilization. In the studied samples, particles larger than 1000 nm, a significant increase in MDD, zeta potential, and loss of homogeneity visible as an increase in the polydispersity index were observed. Most of the samples had PFAT5 above the USP limit (0.05%). Taking into account the obtained data, VP should not be administered with the studied lipid emulsions for parenteral nutrition. Full article

Parenteral nutrition (PN) is a life-sustaining method to provide adequate nutrients to patients unable to receive oral or enteral nutrition. PN typically contains a mixture of macro- and micro-nutrients, although the lipid composition has been identified as a concern for liver disease. Therefore, the study of the intravenous lipid emulsion (ILE) prescribing practices in home-based PN (HPN) patients and whether differing lipid PN alters liver function tests (LFTs) is needed. Methods: A retrospective study of monthly LFTs from a random sample of 105 adult HPN patients in the U.S. over a 6-month period was conducted. Patients were receiving olive oil/soy oil (n = 53, Clinolipid), mixed ILE (n = 39, SMOF Lipid), soy oil (SO; n = 4, Intralipid), or none (n = 7). LFTs monitored were alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (T Bili). Results: No differences were observed in baseline LFTs across groups (all, p > 0.25, η² < 0.04), nor were there differences in age, body mass index, days of PN, or mean PN volume (all, p > 0.36, η² < 0.05). There were no significant interactions between ILE type and time (all p > 0.64, η_p² < 0.03), no effect of ILE type (all p > 0.60, η_p² < 0.03), and no effect of time (all p > 0.69, η_p² < 0.01) in terms of LFTs. Average LFTs over six months were also not different between ILE types (all p > 0.30, η² < 0.04). Conclusion: These findings suggested that patients were mostly prescribed mixed or ILE PN containing more than one lipid source and that differing ILEs in long-term HPN patients did not alter LFTs over a six-month period. Full article

In recent years, an innovative approach has emerged in the field of toxicology for managing acute intoxications caused by lipophilic substances: intravenous lipid emulsions (ILEs). Through numerous experiments and case reports, the efficacy of lipid emulsions in counteracting toxicities induced by lipophilic agents, including a significant number of antiepileptic (AE) drugs, have become increasingly evident. Data spanning a 10-year period (2010–2020) were analyzed by searching through multiple scientific publication platforms like PubMed, Science Direct, Research Gate, and Springer Link. This study focused on reviewing relevant case reports detailing successful intravenous lipid emulsion (ILE) administration in patients with acute intoxications with antiepileptics, specifically examining the impact of fat emulsions on neurological status, Glasgow Coma Scale (GCS) scores, and corrected QT interval concerning hemodynamic instability. The typical symptoms of antiepileptic toxicity include central nervous system depression, ataxia, and nystagmus. Intravenous lipid emulsion application resulted in an increase in Glasgow Coma Scale scores and enhanced recovery from drug intoxication. This study provides a comprehensive overview of the potential utility of ILE as a component to antidote therapy in cases of acute AE poisoning involving neurotropic drugs. The process involves the engagement of various mechanisms of antitoxic activity. Full article

This review summarizes the current understanding of how brevetoxins, produced by Karenia brevis during harmful algal blooms, impact sea turtle health. Sea turtles may be exposed to brevetoxins through ingestion, inhalation, maternal transfer, and potentially absorption through the skin. Brevetoxins bind to voltage-gated sodium channels in the central nervous system, disrupting cellular function and inducing neurological symptoms in affected sea turtles. Moreover, the current evidence suggests a broader and longer-term impact on sea turtle health beyond what is seen during stranding events. Diagnosis relies on the detection of brevetoxins in tissues and plasma from stranded turtles. The current treatment of choice, intravenous lipid emulsion therapy, may rapidly reduce symptoms and brevetoxin concentrations, improving survival rates. Monitoring, prevention, and control strategies for harmful algal blooms are discussed. However, as the frequency and severity of blooms are expected to increase due to climate change and increased environmental pollution, continued research is needed to better understand the sublethal effects of brevetoxins on sea turtles and the impact on hatchlings, as well as the pharmacokinetic mechanisms underlying brevetoxicosis. Moreover, research into the optimization of treatments may help to protect endangered sea turtle populations in the face of this growing threat. Full article

Dextromethorphan (DXM) is used to treat colds and coughs; however, it can cause central nervous system symptoms, such as severe serotonin syndrome (SS). To our knowledge, there is no specific treatment for severe DXM poisoning, and there are no reports on the clinical use of intravenous lipid emulsion (ILE) for its treatment. Herein, we report a case of severe DXM poisoning with SS that was successfully treated with ILE. An older adolescent male visited the emergency department 1 h after ingesting 4500 mg of DXM orally. Physical examination revealed generalized convulsions, muscle rigidity, mydriasis (8.0/8.0 mm), and flushed skin, with a Glasgow Coma Scale score of 8 (E3V1M4). Severe DXM poisoning with SS was diagnosed. The patient was intubated and administered midazolam for continuous convulsions and SS. Activated charcoal was also administered, and body surface cooling was performed. After an 11 h intensive care unit admission, SS with mydriasis (6.0/6.0 mm) did not improve. Subsequently, 1100 mL of 20% soybean oil was injected as an ILE. Mydriasis improved (3.5/3.5 mm) 30 min after ILE administration; simultaneously, blood DXM concentration rapidly increased approximately two-fold. After discontinuing midazolam, the patient’s consciousness signs improved, and he was weaned off the ventilator. SS was cured with no recurrence of convulsions. In cases of DXM poisoning with severe central nervous system disorders, such as SS, ILE treatment can potentially be an effective therapeutic option. For oral overdose cases, where the drug may remain in the intestinal tract, measures such as administering activated charcoal should be taken before administering ILE. Full article

Background: Polytherapy in neonatal and pediatric patients requiring parenteral nutrition (PN) administration is a challenging task. Due to limited intravenous access, the Y-site administration of medication with PN admixtures is sometimes inevitable. Aim: This review aims to summarize the evidence on the compatibility of the Y-site of intravenous medications and PN admixtures in neonatal and pediatric settings. Methods: A literature review of the PubMed database was conducted. Articles published between January 1995 and November 2023 concerning the compatibility of intravenous medications in pediatric-dose PN admixtures or with intravenous lipid emulsions only were included. Studies concerning the compatibility/stability of the ingredients of PN admixtures and those concerning unapproved medications were excluded. Based on the methodology used, the quality of the research was assessed. Results: A total of fifteen studies were explored. Among fifty-five different drug substances assessed in the research reviewed, 56% (31/55) were found to be compatible, 13% (7/55) were assigned as incompatible, and for 31% (17/55), the data were ambiguous. None of the studies demonstrated an “A” grade (very high quality), and the grades “B”, “C”, and “D” were assigned to four, six, and five studies, respectively. The compatibility data are presented in two tables, the first concerning the simultaneous administration of medications with 2-in-1 PN formulations (without lipids) and the second, with 3-in-1 formulations (with lipids) and lipid emulsions. Conclusions: This review presents data on compatibilities between intravenously administered medications and PN mixtures intended for neonates and pediatric patients found in the PubMed database. It should be highlighted, however, that this work has some limitations. The clinical decisions on the simultaneous administration of intravenous medication with PN admixtures should be based not only on this review (including assessment of the quality of evidence) but also on manufacturer data, available electronic databases, and incompatibility data for PN admixtures dedicated to adult patients. Full article

Intestinal failure (IF) is characterized by a critical reduction in functional gut mass below the minimum needed for optimal growth in children. It requires parenteral nutrition (PN) and home-PN (HPN), which is challenging in terms of meeting nutritional needs according to age, growth velocity, clinical situation, and rapid changes in fluid and electrolyte requirements. Due to these complex requirements, age-adapted multi-chamber bags (MCBs) are important additions to the nutrition armamentarium. The launch of composite fish oil (FO)-containing intravenous lipid emulsions (ILEs) heralded the development of MCBs containing these ILEs in combination with a crystalline amino acid solution adapted for pediatric use. The safety and efficacy of lipid and amino acid components in this context have been widely documented in numerous published studies. This narrative manuscript includes a review of the articles published in PudMed, Embase, and Google Scholar up to June 2023 for the age groups of term infants to children and adolescents. Preterm infants with their highly specific demands are not included. It aims to offer an overview of the clinical experience regarding the use of a composite FO-based ILE and a developed specific amino acid solution. Full article

The administration of intravenous lipid emulsion (ILE) is a proven antidote used to reverse local anesthetic-related systemic toxicity. Although the capacity of ILE to generate blood tissue partitioning of lipophilic drugs has been previously demonstrated, a clear recommendation for its use as an antidote for other lipophilic drugs is still under debate. Venlafaxine (an antidepressant acting as a serotonin–norepinephrine reuptake inhibitor (SNRI)) and quetiapine (a second-generation atypical antipsychotic) are widely used in the treatment of psychotic disorders. Both are lipophilic drugs known to induce cardiotoxicity and central nervous depression. We report the case of a 33-year-old man with a medical history of schizoaffective disorder who was admitted to the emergency department (ED) after having been found unconscious due to a voluntary ingestion of 12 g of quetiapine and 4.5 g of venlafaxine. Initial assessment revealed a cardiorespiratory stable patient but unresponsive with a GCS of 4 (M2 E1 V1). In the ED, he was intubated, and gastric lavage was performed. Immediately after the admission to the intensive care unit (ICU), his condition quickly deteriorated, developing cardiovascular collapse refractory to crystalloids and vasopressor infusion. Junctional bradycardia occurred, followed by spontaneous conversion to sinus rhythm. Subsequently, frequent ventricular extrasystoles, as well as patterns of bigeminy, trigeminy, and even episodes of non-sustained ventricular tachycardia, occurred. Additionally, generalized tonic–clonic seizures were observed. Alongside supportive therapy, antiarrhythmic and anticonvulsant therapy, intravenous lipid emulsion bolus, and continuous infusion were administered. His condition progressively improved over the following hours, and 24 h later, he was tapered off the vasopressor. On day 2, the patient repeated the cardiovascular collapse and a second dose of ILE was administered. Over the next few days, the patient’s clinical condition improved, and he was successfully weaned off ventilator and vasopressor support. ILE has the potential to become a form of rescue therapy in cases of severe lipophilic drug poisoning and should be considered a viable treatment for severe cardiovascular instability that is refractory to supportive therapy. Full article

Intestinal failure-associated liver disease (IFALD) is a severe liver injury occurring due to factors related to intestinal failure and parenteral nutrition administration. Different approaches are studied to reduce the risk or ameliorate the course of IFALD, including providing omega-3 fatty acids instead of soybean oil-based lipid emulsion or administering active compounds that exert a hepatoprotective effect. This study aimed to develop, optimize, and characterize magnolol-loaded intravenous lipid emulsion for parenteral nutrition. The preformulation studies allowed for chosen oils mixture of the highest capacity of magnolol solubilization. Then, magnolol-loaded SMOFlipid was developed using the passive incorporation method. The Box–Behnken design and response surface methodology were used to optimize the entrapment efficiency. The optimal formulation was subjected to short-term stress tests, and its effect on normal human liver cells and erythrocytes was determined using the MTT and hemolysis tests, respectively. The optimized magnolol-loaded SMOFlipid was characterized by the mean droplet diameter of 327.6 ± 2.9 nm with a polydispersity index of 0.12 ± 0.02 and zeta potential of −32.8 ± 1.2 mV. The entrapment efficiency of magnolol was above 98%, and pH and osmolality were sufficient for intravenous administration. The magnolol-loaded SMOFlipid samples showed a significantly lower toxic effect than bare SMOFlipid in the same concentration on THLE-2 cells, and revealed an acceptable hemolytic effect of 8.3%. The developed formulation was characterized by satisfactory stability. The in vitro studies showed the reduced cytotoxic effect of MAG-SMOF applied in high concentrations compared to bare SMOFlipid and the non-hemolytic effect on human blood cells. The magnolol-loaded SMOFlipid is promising for further development of hepatoprotective lipid emulsion for parenteral nutrition. Full article

Zinc phosphide is a rodenticide that is used in agricultural, urban and industrial environments in México. After ingestion, it reacts with hydrochloric acid, hydrolyzing into phosphine. It causes cellular hypoxia via mitochondrial toxicity, resulting in multiple organ dysfunction and death. There is no antidote or specific treatment for zinc phosphide toxicity. We present the case of a 45-year-old female who ingested zinc phosphide with suicidal intent. On arrival at the emergency department, she had multisystemic disorders. Supportive care, decontamination and antidotal therapy were initiated. Subsequently, she evolved to clinical improvement with a resolution of the biochemical abnormalities of tissue hypoperfusion. She was discharged on day 7 without complications. In this review, we provide updated therapeutic options and discuss their specific pathophysiological basis. Full article

Intestinal-failure-associated liver disease (IFALD) is a common complication of prolonged parenteral nutrition (PN). Risk factors for IFALD include clinical features, as well as medical interventions, and its management was initially based on the decrease or interruption of parenteral nutrition while increasing enteral nutrition. However, the tolerance of full enteral nutrition in children with intestinal failure may require prolonged intestinal rehabilitation over a period of years. As a consequence, infants unable to wean from PN are prone to develop end-stage liver disease. We describe the case of an infant receiving long-term PN who was diagnosed with IFALD wherein we were able to reverse IFALD by switching lipid emulsions to fish oil monotherapy. A systemic review of case reports and case series on reversing IFALD using fish oil lipid emulsion follows the case description. Full article

Background and objectives: Local anesthetic systemic toxicity (LAST) in children is extremely rare, occurring at an estimated rate of 0.76 cases per 10,000 procedures. However, among reported cases of LAST in the pediatric population, infants and neonates represent approximately 54% of reported LAST cases. We aim to present and discuss the clinical case of LAST with full clinical recovery due to accidental levobupivacaine intravenous infusion in a healthy 1.5-month-old patient, resulting in cardiac arrest necessitating resuscitation. Case presentation: A 4-kilogram, 1.5-month-old female infant, ASA I, presented to the hospital for elective herniorrhaphy surgery. Combined anesthesia was planned, involving general endotracheal and caudal anesthesia. After anesthesia induction, cardiovascular collapse was noticed, resulting in bradycardia and later cardiac arrest with EMD (Electromechanical Dissociation). It was noticed that during induction, levobupivacaine was accidentally infused intravenously. A local anesthetic was prepared for caudal anesthesia. LET (lipid emulsion therapy) was started immediately. Cardiopulmonary resuscitation was carried out according to the EMD algorithm, which lasted 12 min until spontaneous circulation was confirmed and the patient was transferred to the ICU. In ICU, the girl was extubated the second day, and the third day she was transferred to the regular pediatric unit. Finally, the patient was discharged home after a total of five days of hospitalization with full clinical recovery. A four-week follow-up has revealed that the patient recovered without any neurological or cardiac sequelae. Conclusions: The clinical presentation of LAST in children usually begins with cardiovascular symptoms because pediatric patients are already under general anesthesia when anesthetics are being used, as was the case in our case. Treatment and management of LAST involve cessation of local anesthetic infusion, stabilization of the airway, breathing, and hemodynamics, as well as lipid emulsion therapy. Early recognition of LAST as well as immediate CPR if needed and targeted treatment for LAST can lead to good outcomes. Full article