Acute Multiple Organ Failure Research Articles

Postoperative acute multiple organ failure after hepatectomy in a Nigerian male with sickle cell trait: a case report

BackgroundSickle cell disease (SCD) is a monogenic disease characterized by sickle hemoglobin (HbS). Patients homozygous for HbS experience symptoms resulting from sickled erythrocytes no later than adolescence. However, heterozygous HbS carriers, or those with the so-called sickle cell trait (SCT), may undergo surgery without their hemoglobinopathy being known.Case presentationA 53-year-old Nigerian male with hepatitis C infection underwent radiofrequency ablation therapy for multiple hepatocellular carcinomas (HCCs) 17 months prior. Follow-up computed tomography (CT) revealed a solitary tumor (3.2 cm) in the medial section of the cirrhotic liver. The Child–Pugh score was five, and the indocyanine green retention rate at 15 min was 17.4%. The nontumorous liver of the medial section accounted for 10% of the total liver volume according to CT volumetry. With the diagnosis of recurrent HCC, left medial sectionectomy was performed under intermittent blood flow occlusion by Pringle’s maneuver. Intraoperative ultrasonography confirmed that hepatic blood flow had been preserved after hepatectomy. However, laboratory tests on postoperative day (POD) 1 revealed severe liver damage: aspartate aminotransferase 9250 IU/L, alanine aminotransferase 6120 IU/L, total bilirubin 2.8 mg/dL, and prothrombin time% 20.9%. The patient’s renal and respiratory functions also deteriorated; therefore, continuous hemodiafiltration and plasma exchange were initiated under mechanical ventilation. Whole-body contrast-enhanced CT showed no apparent ischemia of the remnant liver, but diffuse cerebral infarction was detected. Despite intensive treatments, he died of multiple organ failure on POD 20. The pathological examination of the resected specimen revealed that the intrahepatic peripheral vessels were occluded by sickled erythrocytes. Additionally, chromatographic analysis of hemoglobin detected the presence of abnormal hemoglobin, although microscopic examination of the peripheral blood erythrocytes did not show morphological abnormalities. Based on these findings, we determined that he had SCT and developed vaso-occlusive crisis involving multiple organs just after hepatectomy.ConclusionSCD is a rare disease in eastern Asia, but its prevalence is increasing globally. Surgeons should pay increased attention to this disease, especially when performing hepatectomy under blood flow occlusion.

Fatal intoxication with PMMA – a novel designer analogue of amphetamine

Abstract Introduction: New designer drugs of the amphetamine class like 4-methoxyamphetamine (PMA) and 4-methoxymethampheta-mine (PMMA) elicit psychoactive effects in the central nervous system (CNS) by enhancing monoaminergic neurotransmission. These substances are substrates for neurotransmitter transporter proteins, and after binding with them they penetrate inside the cells. PMA and PMMA also reverse the transport of endogenic neurotransmitters and stimulate their increased release into the synaptic gap. PMMA has a weaker psychostimulating effect and a stronger hallucinogenic effect than PMA. Materials and methods: The article presents the case of fatal PMMA intoxication in a 28-year-old man. The post-mortem forensic toxicological analysis of collected blood samples was performed using the LC/MS/MS technique. The analysis detected 213 ng/mL of amphetamine, 270 ng/mL of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy), and 4585 ng/mL of PMMA. Results: The cause of death was acute multiple organ failure resulting from heavy intoxication with psychoactive substances, particularly with PMMA.

Metabolomics Analysis in Acute Paraquat Poisoning Patients Based on UPLC-Q-TOF-MS and Machine Learning Approach.

Most paraquat (PQ) poisoned patients died from acute multiple organ failure (MOF) such as lung, kidney, and heart. However, the exact mechanism of intoxication is still unclear. In order to find out the initial toxic mechanism of PQ poisoning, a blood metabolomics study based on ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and efficient machine learning approach was performed on 23 PQ poisoned patients and 29 healthy subjects. The initial PQ plasma concentrations of PQ poisoned patients were >1000 ng/mL, and the blood samples were collected at before first hemoperfusion (HP), after first HP, and after last HP. The results showed that PQ poisoned patients all differed from healthy subjects, whatever they were before or after first HP or after last HP. The efficient machine learning approaches selected key metabolites from three UPLC/Q-TOF-MS data sets which had the highest classification performance in terms of classification accuracy, Matthews Correlation Coefficients, sensitivity, and specificity, respectively. The mass identification revealed that the most important metabolite was adenosine, which sustained in low level, regardless of whether PQ poisoned patients received HP treatment. In conclusion, decreased adenosine was the most important metabolite in PQ poisoned patients. The metabolic disturbance caused by PQ poisoning cannot be improved by HP treatment even the PQ was cleared from the blood.

The effect of fractal-like mechanical ventilation on vital signs in a rat model of acute-on-chronic liver failure

Objective: The network of interactions between different organs is impaired in liver cirrhosis. Liver cirrhosis is associated with multi-system involvement, which eventually leads to multiple organ failure. This process is accelerated by a precipitating factor such as bacterial infection, which leads to respiratory distress, circulatory shock, neural dysfunction and very high mortality. Cirrhotic patients often have blunted respiratory sinus arrhythmia and impaired cardio-respiratory variability. Fractal-like mechanical ventilation is reported to enhance respiratory sinus arrhythmia and attenuate respiratory distress in experimental models. In the present study we hypothesise that fractal-like mechanical ventilation may improve the outcome of cirrhotic rats with multiple organ failure. Approach: Cirrhosis was induced by chronic biliary obstruction in rats. Acute multiple organ failure was induced by intraperitoneal injection of bacterial endotoxin in cirrhotic rats. The effect of conventional mechanical ventilation (with constant tidal volume and respiratory rate) or fractal-like ventilation (with the same average but variable tidal volume and respiratory rate) were assessed on vital signs, oxygen saturation and plasma alanine aminotransferase in anaesthetised cirrhotic rats. Main results: We demonstrated that fractal-like mechanical ventilation was accompanied by improved oxygen saturation, reduced heart rate and decreased liver injury following injection of bacterial endotoxin. Moreover, variable mechanical ventilation in cirrhotic rats reduced mortality and prevented a fall in short-term heart rate variability following endotoxin challenge in comparison with rats with constant mechanical ventilation. Significance: We suggest further investigations into the beneficial effects of fractal-like ventilation strategy in critically ill patients with liver failure requiring organ support and mechanical ventilation.

Cholesterol metabolites alleviate injured liver function and decrease mortality in an LPS-induced mouse model

BackgroundOxysterol sulfation plays a fundamental role in the regulation of many biological events. Its products, 25-hydroxycholesterol 3-sulfate (25HC3S) and 25-hydroxycholesterol 3, 25-disulfate (25HCDS), have been demonstrated to be potent regulators of lipid metabolism, inflammatory response, cell apoptosis, and cell survival. In the present study, we tested these products' potential to treat LPS-induced acute liver failure in a mouse model. MethodsAcute liver failure mouse model was established by intravenous injection with LPS. The injured liver function was treated with intraperitoneal administration of 25HC, 25HC3S or 25HCDS. Serum enzymatic activities were determined in our clinic laboratory. ELISA assays were used to detect pro-inflammatory factor levels in sera. Western blot, Real-time Quantitative PCR and RT2 Profiler PCR Array analysis were used to determine levels of gene expression. ResultsAdministration of 25HC3S/25HCDS decreased serum liver-impaired markers; suppressed secretion of pro-inflammatory factors; alleviated liver, lung, and kidney injury; and subsequently increased the survival rate in the LPS-induced mouse model. These effects resulted from the inhibition of the expression of genes involved in the pro-inflammatory response and apoptosis and the simultaneous induction of the expression of genes involved in cell survival. Compared to 25HC, 25HC3S and 25HCDS exhibited significantly stronger effects in these activities, indicating that the cholesterol metabolites play an important role in the inflammatory response, cell apoptosis, and cell survival in vivo. Conclusions25HC3S/25HCDS has potential to serve as novel biomedicines in the therapy of acute liver failure and acute multiple organ failure.

Acute Multiple Organ Failure in Adult Mice Deleted for the Developmental Regulator Wt1

There is much interest in the mechanisms that regulate adult tissue homeostasis and their relationship to processes governing foetal development. Mice deleted for the Wilms' tumour gene, Wt1, lack kidneys, gonads, and spleen and die at mid-gestation due to defective coronary vasculature. Wt1 is vital for maintaining the mesenchymal–epithelial balance in these tissues and is required for the epithelial-to-mesenchyme transition (EMT) that generates coronary vascular progenitors. Although Wt1 is only expressed in rare cell populations in adults including glomerular podocytes, 1% of bone marrow cells, and mesothelium, we hypothesised that this might be important for homeostasis of adult tissues; hence, we deleted the gene ubiquitously in young and adult mice. Within just a few days, the mice suffered glomerulosclerosis, atrophy of the exocrine pancreas and spleen, severe reduction in bone and fat, and failure of erythropoiesis. FACS and culture experiments showed that Wt1 has an intrinsic role in both haematopoietic and mesenchymal stem cell lineages and suggest that defects within these contribute to the phenotypes we observe. We propose that glomerulosclerosis arises in part through down regulation of nephrin, a known Wt1 target gene. Protein profiling in mutant serum showed that there was no systemic inflammatory or nutritional response in the mutant mice. However, there was a dramatic reduction in circulating IGF-1 levels, which is likely to contribute to the bone and fat phenotypes. The reduction of IGF-1 did not result from a decrease in circulating GH, and there is no apparent pathology of the pituitary and adrenal glands. These findings 1) suggest that Wt1 is a major regulator of the homeostasis of some adult tissues, through both local and systemic actions; 2) highlight the differences between foetal and adult tissue regulation; 3) point to the importance of adult mesenchyme in tissue turnover.

Acute multiple organ failure with imidacloprid and alcohol ingestion

Imidacloprid [1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine] belongs to a relatively new class of insecticidal chemistry, the chloronicotinyl neonicotinoid compounds. Animal studies indicate relatively low toxicity to mammals due to nicotinic receptor resistance. Human poisoning is usually mild, and reports are quite limited. Here, we report a case of ingestion of alcohol with an insecticide containing imidacloprid. Clinical manifestation included mild disorientation, followed by bradycardia, ventricular arrhythmia, and cardiopulmonary arrest. Acute multiple organ failure, including oliguric kidney injury, acute lung injury, hypotension, and metabolic acidosis developed within hours of ingestion. Renal replacement therapy, including intermittent hemodialysis and continuous venovenous hemodialysis, quickly corrected the metabolic acidosis with better blood pressure. Despite original belief that imidacloprid has low mammalian toxicity, there is increasing evidence that imidacloprid may cause heart, kidney, and other organ damages and even death besides gastrointestinal irritation and neurological symptoms. The role of aldehyde oxidase, imidacloprid metabolites, and ethanol alcohol consumption in the pathogenesis of imidacloprid toxicity needs further study.

Fatal allergic vasculitis associated with celecoxib

We report on the occurrence of a rare and as yet unforseeable adverse reaction to treatment with celecoxib, a cyclooxygenase-2 (COX-2) selective, non-steroidal, anti-inflammatory drug. A previously healthy adult suffered fatal acute multiple organ failure presumably after diffuse allergic vasculitis with diffuse necrotic purpura. Although no conclusive proof is available, such a reaction could have been triggered by at least one of two mechanisms: an allergic reaction linked to the chemical structure of celecoxib; or an interaction of the drug with synthesis of endothelial eiconasoids leading to an imbalance between vasoactive end products, resulting in widespread rise to local thrombosis.

Moyens mécaniques de traitement de l'insuffisance cardiaque réfractaire

Mechanical means tend to be used more frequently nowadays for the treatment of congestive heart failure which does not respond to more normal treatment. The indications and limits of such devices, as well as their cost, must be defined. The new problem created by these therapeutic tools is the evolution of the underlying cardiac disease : should it improve the patient will be weaned from the machine, whereas if it worsens heart transplantation would be the only answer. Three types of mechanical support are described. Balloon pumping, and especially intra-aortic balloon pumping, is the technique used most often. It has a true but limited efficacy. Its best indication is cardiogenic shock by left ventricular ischaemia with normal or slightly increased peripheral resistances. Intrapulmonary balloon pumping is occasionally used, but the system can only be set up surgically. Its best indication would seem to be right-sided heart failure by pulmonary hypertension. Circulatory assistance is the second type considered. All types of bypass pumps can be used. The output used is usually less than the patient's theoretical output, the aim being to allow the myocardium to recover. Vascular access for these pumps is either femoral or intrathoracic. An oxygenator may or may not be added to the bypass circuit, and support may be mono- or biventricular. Although the non pulsatile flow has not been shown to be detrimental, this has to be investigated further. The use of these devices is limited by their effects on blood coagulation and pulmonary function. The artificial heart or artificial ventricles are the last devices described. They are either orthotopic, such as the Jarvik type, or extracorporeal, such as the Pierce artificial ventricles. Their ability to support totally the circulation for weeks allows patients to recover somewhat from acute multiple organ failure, so that they can be transplanted in better conditions. The main difficulty in using such devices is patient selection, with the exclusion straight-off of those patients with chronic multiple organ failure who will in any case not be suitable for transplantation later on. Because there are numerous mechanical means now available for the treatment of congestive heart failure no longer responsive to drugs, the choice of device to be used depends on the ultimate goal aimed for, i.g. transplantation or not.