A 68-Year-Old Man with Depression and Acute Renal Failure Due to Rhabdomyolysis Associated with Alcohol Intoxication While Taking Low-Dose Escitalopram: A Case Report.

BACKGROUND Rhabdomyolysis, an uncommon but recognized adverse effect of selective serotonin reuptake inhibitor (SSRI) antidepressants, can precipitate acute renal injury (AKI), especially when combined with risk factors such as alcohol consumption. This report describes a 68-year-old man with acute renal failure due to rhabdomyolysis associated with alcohol intoxication while taking low-dose escitalopram, an SSRI antidepressant. CASE REPORT The patient, with a history of bipolar affective disorder managed with escitalopram, presented with symptoms of general malaise, diarrhea, myalgias, and transient loss of consciousness following substantial ethanol consumption. Laboratory tests indicated severe rhabdomyolysis with a creatine kinase level of 37 672 U/L and myoglobin level >5710 ng/ml, leading to an AKI diagnosis. The discontinuation of escitalopram, along with hydration and renal replacement therapy, facilitated renal recovery. However, the reintroduction of escitalopram resulted in the recurrence of rhabdomyolysis, suggesting a probable causal link, confirmed using the Naranjo Adverse Drug Reaction Probability Scale. CONCLUSIONS This report highlights the importance of identifying the medication history in patients presenting with acute renal failure and rhabdomyolysis and the association with SSRIs, which can be exacerbated by alcohol. This case underscores the importance of vigilant medication history assessment in patients presenting with AKI and rhabdomyolysis, particularly concerning the use of SSRIs like escitalopram, which can pose heightened risks in the context of alcohol use. It highlights the need for clinical caution in managing patients on long-term SSRI therapy, especially when reintroducing such medications after an episode of rhabdomyolysis.

A systematic review of the drug-drug interaction between Statins and Quinolones.

BACKGROUND: Statins are widely used in cardiovascular disease (CVD) as a common lipid-lowering drug, while quinolones are widely used for the treatment of infectious diseases. It is common to see CVD in combination with infectious diseases, therefore it is often the case that statins and quinolones are used in combination. Data suggest combinations of statin and quinolone may be associated with potentially life-threatening myopathy, rhabdomyolysis and acute hepatitis. This systematic review aims to characterize data regarding patients affected by the statin-quinolone interaction. METHODS: The purpose of this systematic review was to collect and evaluate the evidence surrounding statin-quinolone drug interactions and to discuss related risk mitigation strategies. The following databases were searched: PubMed (Medline), Embase, Scopus, and Cochrane Library. The systematic electronic literature search was conducted with the following search terms. In this study, three types of search terms were used: statins-related terms, quinolones-related terms, and drug interactions-related terms. RESULTS: There were 16 case reports that met the criteria for qualitative analysis. Patients were involved in the following adverse reactions: rhabdomyolysis (n = 12), acute hepatitis (n = 1), muscle weakness (n = 1), hip tendinopathy (n = 1), or myopathy (n = 1). In the included literature, patients vary in the dose and type of statins they take, including simvastatin (n = 10) at a dose range of 20-80 mg/d and atorvastatin (n = 4) at a dose of 80 mg/d. There were 2 patients with unspecified statin doses, separately using simvastatin and atorvastatin. The quinolones in combination were ciprofloxacin (n = 9) at a dose range of 800-1500 mg/d, levofloxacin (n = 6) at a dose range of 250-1000 mg/d, and norfloxacin (n = 1) in an unspecified dose range. 81% of the case patients were over 60 years of age, and about 1/3 had kidney-related diseases such as diabetic nephropathy, post-transplantation, and severe glomerulonephritis. Nearly two-third of the patients were on concomitant cytochrome P450 3A4 (CYP3A4) inhibitors, P-glycoprotein (P-gp) inhibitors, or organic anion transporting polypeptide 1B1 (OATP1B1) inhibitors. CONCLUSION: Patients treated with statin-quinolone combination should be monitored more closely for changes in aspartate aminotransferase or creatine kinase (CK) levels, and muscle symptoms, especially in patients with ciprofloxacin or levofloxacin, with simvastatin and high-dose atorvastatin, over 60 years of age, with kidney-related diseases, and on concomitant CYP3A4 inhibitors.

Rhabdomyolysis Risk: The Dangers of Tribulus Terrestris, an Over-the-Counter Supplement.

BACKGROUND Over-the-counter (OTC) supplement use is a very common practice within the United States. Supplements are not tightly regulated by the Food and Drug Administration. There are many case reports involving OTC supplement adverse effects and medication interactions, but there remains minimal clinical research regarding these subjects. Rhabdomyolysis is one interaction and adverse effect frequently documented in case reports among a variety of OTC supplements, although, to date, there is no documentation of rhabdomyolysis occurring from an interaction between the supplement Tribulus terrestris and atorvastatin. CASE REPORT A 71-year-old man presented to the Emergency Department in rhabdomyolysis with a mild transaminitis after taking the over-the-counter supplement Tribulus terrestris while on long-term atorvastatin. His rhabdomyolysis peaked at day 4 after cessation of the Tribulus and atorvastatin and aggressive fluid resuscitation with a normal saline bolus at admission followed by a D5 sodium bicarbonate drip later transitioned to a normal saline drip with subsequent down-trending of the creatinine phosphokinase levels. CONCLUSIONS Tribulus terrestris is an herbal supplement used for erectile dysfunction and energy. Recent research suggests it to be a moderate CYP 3A4 inhibitor that plays a significant role in metabolism of statin and many other commonly prescribed medications. This may put patients at increased risk of developing serious adverse effects, including rhabdomyolysis and drug-induced liver injury. Screening patients for over-the-counter supplement use and educating them on the potential risks of their use is extremely important for inpatient and outpatient healthcare professionals to avoid dangerous medication interactions.

Pregabalin-induced rhabdomyolysis: a case series and literature analysis.

Pregabalin is a prescription medicine that has recently been approved for individuals who suffer from fibromyalgia, neuropathic pain, anxiety disorder, or epilepsy. Pregabalin has the side effects of dizziness, sleepiness, and angioedema. Pregabalin-induced rhabdomyolysis has been rarely reported, with only four reports to date. We report two cases of rhabdomyolysis after pregabalin treatment. A man aged older than 90 years presented with exhaustion, muscle aches, and a high serum creatine kinase concentration after taking 75 mg of pregabalin on the first day of treatment. A woman in her 90s with long-term use of pregabalin presented with considerably elevated serum creatine kinase concentrations. Both patients had a long history of taking statins. Pregabalin therapy was stopped, high-volume intravenous fluids were administered, and serum electrolytes were frequently checked. Alkalinisation was performed with excellent outcomes. The Naranjo Adverse Drug Reaction scale and previous research suggest an association between pregabalin and rhabdomyolysis. Clinicians should be alert to the possibility of rhabdomyolysis occurring with the use of pregabalin, especially when taking statins.

Paralumbar compartment syndrome, a rare sequela of deadlifting: a case report and review of current literature.

BACKGROUND: Compartment syndrome is a well-known phenomenon that is most commonly reported in the extremities. However, paralumbar compartment syndrome is rarely described in available literature. The authors present a case of paralumbar compartment syndrome after high intensity deadlifting. CASE PRESENTATION: 53-year-old male who presented with progressively worsening low back pain and paresthesias one day after high-intensity deadlifting. Laboratory testing found the patient to be in rhabdomyolysis; he was admitted for intravenous fluid resuscitation and pain control. Orthopedics was consulted, and Magnetic Resonance Imaging revealed significant paravertebral edema and loss of muscle striation. Given the patient's lack of improvement with intravenous and oral pain control, clinical and radiographic findings, there was significant concern for acute paralumbar compartment syndrome. The patient subsequently underwent urgent fasciotomy of bilateral paralumbar musculature with delayed closure. CONCLUSION: Given the paucity of literature on paralumbar compartment syndrome, the authors' goal is to promote awareness of the diagnosis, as it should be included in the differential diagnosis of intractable back pain after high exertional exercise. The current literature suggests that operative cases of paralumbar compartment syndromes have a higher rate of return to pre-operative function compared to those treated non-operatively. This case report further supports this notion. The authors recommend further study into this phenomenon, given its potential to result in persistent chronic exertional pain and irreversible tissue damage.

Rhabdomyolysis and acute kidney injury after consumption of black seed oil.

PURPOSE: Medicines derived from natural sources have been used for thousands of years throughout the world. Because natural compounds are thought to have less toxic effects and fewer side effects, these products are becoming more popular by the day. CASE REPORT: In this case report, we presented a case of acute kidney injury, rhabdomyolysis, and hepatotoxicity after ingestion of black seed oil. Although black seed oil is widely used around the world, there is currently limited knowledge on its adverse effects. CONCLUSION: It is important to keep in mind that rhabdomyolysis, acute renal damage, and hepatotoxicity might occur following the use of black seed oil. Black seed oil ingestion should be considered when making a differential diagnosis for these conditions in patients suspected of taking herbal products.

Boswellia serrata intoxication manifesting with syndrome of inappropriate antidiuretic hormone secretion, hyponatremia, seizure, and rhabdomyolysis.

Boswellia serrata is an herbal extract from the Boswellia serrata tree that has anti-inflammatory and analgesic properties and alleviates pain caused by rheumatoid arthritis, gout, osteoarthritis, and sciatica. Syndrome of inappropriate antidiuretic hormone secretion accompanied by hyponatremia, seizures, and rhabdomyolysis as a manifestation of Boswellia serrata intoxication has not been reported previously. A 38-year-old female suffered clinically isolated syndrome and has since been regularly taking B. serrata capsules (200mg/d) to strengthen her immune system. She experienced hypersensitivity to light, ocular pain, nausea, dizziness, and lower limb weakness four days after receiving her first BNT162b2 vaccine dose, and she increased the dosage of B. serrata to five capsules (1000mg/d) one week after vaccination. After taking B. serrata at a dosage of 1000mg/d for 3 weeks, she was admitted to the intensive care unit because of a first, unprovoked generalized tonic-clonic seizure. The patient's workup revealed syndrome of inappropriate antidiuretic hormone secretion, which resolved completely upon treatment and discontinuation of B. serrata. In summary, B. serrata potentially causes syndrome of inappropriate antidiuretic hormone secretion when it is taken at high doses. Patients should not self-medicate.

Rhabdomyolysis secondary to a weight-loss prescription.

We present a case of a case of a man in his 70s on multiple medications (including treatment of ischemic heart disease and diabetes who developed significant rhabdomyolysis, complicated by acute kidney injury (AKI) and encephalopathy, while using a compounded medication for weight loss. The patient was admitted to the intensive care unit and progressed favourably after haemodialysis and supportive care. Information regarding the ingestion of weight-loss drugs was unknown at the time of admission and was only discovered after resolution of encephalopathy, raising the possibility of toxin-associated rhabdomyolysis. This case emphasises the need for a thorough clinical history and scrutiny of the safety of weight-loss prescriptions, including preparations that comprise a combination of drugs and supplements that may adversely interact with chronic medications, especially in polymedicated patients.

Spurious hyperbicarbonatemia and a negative anion gap in a cat and a dog with severe rhabdomyolysis.

A 3-year-old male neutered domestic shorthair cat and a 2-year-old male neutered Labrador-mix dog were separately presented to the Veterinary Medical Center for evaluation after sustaining significant muscle trauma due to a dog attack and seizure activity, respectively. In both cases, biochemical analysis was consistent with rhabdomyolysis. Additionally, a markedly increased measured serum bicarbonate concentration and negative calculated anion gap were observed. As these biochemical abnormalities were not expected and deemed incompatible with life, an interference with the analyzer measurement of bicarbonate involving marked increases in pyruvate and lactate dehydrogenase (LDH) following myocyte injury was suspected. Venous blood gas analysis calculated bicarbonate concentration and anion gap were within reference interval, while measured LDH activity was markedly increased. These findings supported an analyzer-generated interference. This is the first published report of a previously described chemistry analyzer interference of markedly increased LDH activity with serum bicarbonate concentration measurement in dogs and cats. Awareness of this interference is important, particularly in the emergency setting, as it may influence case management.

Clinical presentation and outcomes of patients with rhabdomyolysis: A tertiary care center experience.

OBJECTIVES: To evaluate the clinical and laboratory features, complications, and outcomes of patients with rhabdomyolysis in the Saudi population. METHODS: Retrospectives descriptive study of adult patients who presented to King Abdulaziz Medical City (KAMC) withrhabdomyolysis between January 2016 and December 2022. RESULTS: Most of the participants (84.5%) were male, with a median age of 41 years and a body mass index of 26.5 kg/m2. Medications, mainly statins (22.4%) and illicit drugs (15.5%), constituted the root causes of rhabdomyolysis in the cohort (44.8%). The most common presenting complaints were myalgia (63.8%) and fatigue (37.9%). More than one-third of the participants (32.8%) developed AKI, with 3 patients requiring temporary hemodialysis, and only 8.6% developed acute liver failure (ALF). Intensive care unit (ICU) admission was required for 10 patients (17.2%), and the overall mortality rate was 8.6%. Patients who developed complications (composite outcomes of AKI, ALF, multiorgan failure, or death) had significantly reduced kidney function and higher levels of blood urea nitrogen, anion gap, and uric acid upon admission than those who did not. CONCLUSION: This study offers a thorough understanding of clinical and laboratory features, causes, complications, and outcomes of rhabdomyolysis among Saudi patients. The insights gained enhance our understanding of rhabdomyolysis within this population, providing a foundation for future research and improvements in clinical management.

D-Bifunctional Protein Deficiency Diagnosis-A Challenge in Low Resource Settings: Case Report and Review of the Literature.

D-bifunctional protein deficiency (D-BPD) is a rare, autosomal recessive peroxisomal disorder that affects the breakdown of long-chain fatty acids. Patients with D-BPD typically present during the neonatal period with hypotonia, seizures, and facial dysmorphism, followed by severe developmental delay and early mortality. While some patients have survived past two years of age, the detectable enzyme activity in these rare cases was likely a contributing factor. We report a D-BPD case and comment on challenges faced in diagnosis based on a narrative literature review. An overview of Romania's first patient diagnosed with D-BPD is provided, including clinical presentation, imaging, biochemical, molecular data, and clinical course. Establishing a diagnosis can be challenging, as the clinical picture is often incomplete or similar to many other conditions. Our patient was diagnosed with type I D-BPD based on whole-exome sequencing (WES) results revealing a pathogenic frameshift variant of the HSD17B4 gene, c788del, p(Pro263GInfs*2), previously identified in another D-BPD patient. WES also identified a variant of the SUOX gene with unclear significance. We advocate for using molecular diagnosis in critically ill newborns and infants to improve care, reduce healthcare costs, and allow for familial counseling.

Exertional rhabdomyolysis among active component members of the U.S. Armed Forces, 2019-2023.

A largely preventable condition, exertional rhabdomyolysis persists as an occupational hazard of military training and operations, especially in high heat environments among individuals exerting themselves to their physical endurance limits. During the 5-year surveillance period of this study, unadjusted incidence rates of exertional rhabdomyolysis per 100,000 person-years among U.S. active component service members fluctuated, reaching a low of 38.0 cases in 2020 and peaking at 40.5 cases in 2023. The rate in 2020 constituted a decline of 3.8% from the rate in 2019 (39.5 cases). Beginning in 2020, incidence rates per 100,000 person-years gradually increased, by 1.8% in 2021 (38.7 cases), 5.3% in 2022 (40.0 cases), and 6.6% in 2023 (40.5 cases). Consistent with prior reports, subgroup-specific crude rates in 2023 were highest among men, those less than 20 years old, non-Hispanic Black service members, Marine Corps or Army members, and those in combat-specific and 'other' occupations. Recruits experienced the highest rates of exertional rhabdomyolysis during each year, with incidence rates 6 to 10 times greater than all other service members.

Genome-Wide Analysis of Exertional Rhabdomyolysis in Sickle Cell Trait Positive African Americans.

Sickle cell trait (SCT), although generally a benign carrier state of hemoglobin S (HbAS), is a risk factor for exertional rhabdomyolysis (ERM), a rare but potentially fatal consequence of highly intense physical exercise, particularly among active-duty military personnel and high-performance athletes. The association between SCT and ERM is poorly understood. The objective of this study was to elucidate the genetic basis of ERM in an SCT-positive African American cohort. SCT-positive African Americans with a personal history of ERM (cases, n = 30) and without history of ERM (controls, n = 53) were enrolled in this study. Whole-genome sequencing was performed on DNA samples isolated from peripheral white blood cells. Participants' demographic, behavioral, and medical history information was obtained. An additional 131 controls were extracted from SCT-positive subjects of African descent from the 1000 Genomes Project. SCT carriers with ERM were characterized by myotoxicity features, significant muscle involvement dominated by muscle weakness, and severe pain and substantial increase in serum creatine kinase, with a mean value of 50,480 U/L. A distinctive feature of the SCT individuals with ERM was exertional collapse, which was reported in 53.3% of the cases in the study cohort. An important factor for the development of ERM was the duration and frequency of strenuous physical activity in the cases compared to the controls. Whole-genome sequencing identified 79,696 protein-coding variants. Genome-wide association analysis revealed that the p.C477R, rs115958260 variant in the SLC44A3 gene was significantly associated with ERM event in SCT-positive African Americans. The study results suggest that a combination of vigorous exercise and a genetic predisposing factor is involved in ERM.

Identifying Drug-Drug Interactions in Spontaneous Reports Utilizing Signal Detection and Biological Plausibility Aspects.

Translational approaches can benefit post-marketing drug safety surveillance through the growing availability of systems pharmacology data. Here, we propose a novel Bayesian framework for identifying drug-drug interaction (DDI) signals and differentiating between individual drug and drug combination signals. This framework is coupled with a systems pharmacology approach for automated biological plausibility assessment. Integrating statistical and biological evidence, our method achieves a 16.5% improvement (AUC: from 0.620 to 0.722) with drug-target-adverse event associations, 16.0% (AUC: from 0.580 to 0.673) with drug enzyme, and 15.0% (AUC: from 0.568 to 0.653) with drug transporter information. Applying this approach to detect potential DDI signals of QT prolongation and rhabdomyolysis within the FDA Adverse Event Reporting System (FAERS), we emphasize the significance of systems pharmacology in enhancing statistical signal detection in pharmacovigilance. Our study showcases the promise of data-driven biological plausibility assessment in the context of challenging post-marketing DDI surveillance.

Early diagnosis and treatment by newborn screening (NBS) or family history is associated with improved visual outcomes for long-chain 3-hydroxyacylCoA dehydrogenase deficiency (LCHADD) chorioretinopathy.

Long chain 3-hydroxyacyl-CoA dehydrogenase (LCHADD) is the only fatty acid oxidation disorder to develop a progressive chorioretinopathy resulting in vision loss; newborn screening (NBS) for this disorder began in the United States around 2004. We compared visual outcomes among 40 participants with LCHADD or trifunctional protein deficiency diagnosed symptomatically to those who were diagnosed via NBS or a family history. Participants completed ophthalmologic testing including measures of visual acuity, electroretinograms (ERG), fundal imaging, contrast sensitivity, and visual fields. Records were reviewed to document medical and treatment history. Twelve participants presented symptomatically with hypoglycemia, failure to thrive, liver dysfunction, cardiac arrest, or rhabdomyolysis. Twenty eight were diagnosed by NBS or due to a family history of LCHADD. Participants diagnosed symptomatically were older but had similar percent males and genotypes as those diagnosed by NBS. Treatment consisted of fasting avoidance, dietary long-chain fat restriction, MCT, C7, and/or carnitine supplementation. Visual acuity, rod- and cone-driven amplitudes on ERG, contrast sensitivity scores, and visual fields were all significantly worse among participants diagnosed symptomatically compared to NBS. In mixed-effects models, both age and presentation (symptomatic vs. NBS) were significant independent factors associated with visual outcomes. This suggests that visual outcomes were improved by NBS, but there was still lower visual function with advancing age in both groups. Early diagnosis and treatment by NBS is associated with improved visual outcomes and retinal function compared to participants who presented symptomatically. Despite the impact of early intervention, chorioretinopathy was greater with advancing age, highlighting the need for novel treatments.

Acute lumbar paraspinal compartment syndrome after radical cystectomy.

Lumbar paraspinal compartment syndrome (LPCS) is a rare diagnosis, seen in patients chronically after repeated lumbar trauma or acutely in a postoperative setting. Only a dozen cases are documented worldwide, and to date no clinical guidelines exist for the diagnosis nor the treatment.We describe the case of a 44-year-old man with excruciating lower back pain following a radical cystectomy. The postoperative laboratory values were compatible with acute rhabdomyolysis. The lumbar spine MRI showed necrosis of lumbosacral paraspinal muscles, making the diagnosis of acute LPCS. After seeking advice from different specialists, the conservative approach was chosen with combined pain treatment and physiotherapy. The patient is currently still disabled for some tasks and needs chronic pain medication.

Time-to-onset Analysis of Rhabdomyolysis due to Different Proton Pump Inhibitors Using a Pharmacovigilance Database.

BACKGROUND/AIM: Recent research has increasingly demonstrated an association between proton pump inhibitors (PPIs) and serious adverse events. This study aimed to evaluate the association between PPI and rhabdomyolysis (RM), examining its time-to-onset profiles using the Japanese Adverse Drug Event Report (JADER) database. PATIENTS AND METHODS: Data spanning from April 2004 to March 2022 were used. The association between PPIs and RM was evaluated using the reporting odds ratio (ROR), adjusted for sex and age. Subsequent analyses were conducted after excluding cases involving concomitant use of statins or fibrates. Furthermore, the onset time of RM and Weibull distribution parameters were calculated to evaluate the expression profile of RM, and the outcomes were examined. RESULTS: RM was associated with the use of esomeprazole, omeprazole, and rabeprazole, even in the absence of concomitant statin or fibrate use. The median time to RM onset varied among PPIs, ranging from 6.5 to 127 d. The Weibull distribution parameters indicated that the hazard types of nearly all orally administered PPIs were classified as early failure or close to random failure. Regarding outcomes, cases of death were reported for all PPIs except vonoprazan. CONCLUSION: The findings suggest the need for vigilant monitoring of RM during PPI administration, particularly in the early stages, considering the varying onset times.

Advancing Adverse Drug Reaction Prediction with Deep Chemical Language Model for Drug Safety Evaluation.

The accurate prediction of adverse drug reactions (ADRs) is essential for comprehensive drug safety evaluation. Pre-trained deep chemical language models have emerged as powerful tools capable of automatically learning molecular structural features from large-scale datasets, showing promising capabilities for the downstream prediction of molecular properties. However, the performance of pre-trained chemical language models in predicting ADRs, especially idiosyncratic ADRs induced by marketed drugs, remains largely unexplored. In this study, we propose MoLFormer-XL, a pre-trained model for encoding molecular features from canonical SMILES, in conjunction with a CNN-based model to predict drug-induced QT interval prolongation (DIQT), drug-induced teratogenicity (DIT), and drug-induced rhabdomyolysis (DIR). Our results demonstrate that the proposed model outperforms conventional models applied in previous studies for predicting DIQT, DIT, and DIR. Notably, an analysis of the learned linear attention maps highlights amines, alcohol, ethers, and aromatic halogen compounds as strongly associated with the three types of ADRs. These findings hold promise for enhancing drug discovery pipelines and reducing the drug attrition rate due to safety concerns.

Super-refractory status epilepticus, rhabdomyolysis, central hyperthermia and cardiomyopathy attributable to spinal anesthesia: a case report and review of literature.

BACKGROUND: There are only six past reports of super-refractory status epilepticus induced by spinal anesthesia. None of those patients have died. Only < 15 mg of bupivacaine was administered to all six of them and to our case. Pathophysiology ensuing such cases remains unclear. CASE PRESENTATION: A 27 year old gravida 2, para 1, mother at 37 weeks of gestation came to the operating theater for an elective cesarean section. She had no significant medical history other than controlled hypothyroidism and one episode of food allergy. Her current pregnancy was uneventful. Her American Society of Anesthesiologists (ASA) grade was 2. She underwent spinal anesthesia and adequate anesthesia was achieved. After 5-7 min she developed a progressive myoclonus. After delivery of a healthy baby, she developed generalized tonic clonic seizures that continued despite the induction of general anesthesia. She had rhabdomyolysis, one brief cardiac arrest and resuscitation, followed by stress cardiomyopathy and central hyperthermia. She died on day four. There were no significant macroscopic or histopathological changes in her brain that explain her super refractory status epilepticus. Heavy bupivacaine samples of the same batch used for this patient were analyzed by two specialized laboratories. National Medicines Quality Assurance Laboratory of Sri Lanka reported that samples failed to confirm United States Pharmacopeia (USP) dextrose specifications and passed other tests. Subsequently, Therapeutic Goods Administration of Australia reported that the drug passed all standard USP quality tests applied to it. Nonetheless, they have detected an unidentified impurity in the medicine. CONCLUSIONS: After reviewing relevant literature, we believe that direct neurotoxicity by bupivacaine is the most probable cause of super-refractory status epilepticus. Super-refractory status epilepticus would have led to her other complications and death. We discuss probable patient factors that would have made her susceptible to neurotoxicity. The impurity in the drug detected by one laboratory also would have contributed to her status epilepticus. We propose several possible mechanisms that would have led to status epilepticus and her death. We discuss the factors that shall guide investigators on future such cases. We suggest ways to minimize similar future incidents. This is an idiosyncratic reaction as well.

Major clinical events and healthcare resource use among patients with long-chain fatty acid oxidation disorders in the United States: Results from LC-FAOD Odyssey program.

Major clinical events (MCEs) related to long-chain fatty acid oxidation disorders (LC-FAOD) in triheptanoin clinical trials include inpatient or emergency room (ER) visits for three major clinical manifestations: rhabdomyolysis, hypoglycemia, and cardiomyopathy. However, outcomes data outside of LC-FAOD clinical trials are limited. The non-interventional cohort LC-FAOD Odyssey study examines data derived from US medical records and patient reported outcomes to quantify LC-FAOD burden according to management strategy including MCE frequency and healthcare resource utilization (HRU). Thirty-four patients were analyzed of which 21 and 29 patients had received triheptanoin and/or medium chain triglycerides (MCT), respectively. 36% experienced MCEs while receiving triheptanoin versus 54% on MCT. Total mean annualized MCE rates on triheptanoin and MCT were 0.1 and 0.7, respectively. Annualized disease-related inpatient and ER events were lower on triheptanoin (0.2, 0.3, respectively) than MCT (1.2, 1.0, respectively). Patients were managed more in an outpatient setting on triheptanoin (8.9 annualized outpatient visits) vs MCT (7.9). Overall, this shows that those with LC-FAOD in the Odyssey program experienced fewer MCEs and less HRU in inpatient and ER settings during triheptanoin-treated periods compared with the MCT-treated periods. The MCE rate was lower after initiation of triheptanoin, consistent with clinical trials.