Bupivacaine-Induced Hepatotoxicity in a Healthy Patient Without Chronic Liver Disease After Shoulder Arthroscopy

Introduction: Bupivacaine is a local anesthetic which has been increasingly used in the post-operative state for pain control. Hepatotoxicity is a rare complication, and few cases are reported in patients with chronic liver disease. We present a case of acute liver injury from bupivacaine use in a healthy patient without prior history of liver disease. Case Description/Methods: A 68-year-old female with a past medical history of primary hypertension and recent nontraumatic complete tear of the right rotator cuff, presents to the hospital with fatigue, loss of appetite, and nausea. She recently underwent an arthroscopy of the right shoulder with repair of the rotator cuff two weeks prior. Her surgery was uncomplicated, and patient was started on bupivacaine ONQ pump infusion at 5 ml/hr for three days for post-operative pain. Further history reveals patient is non-alcoholic without prior liver disease, including cirrhosis. Review of systems is concerning for associated generalized abdominal discomfort. Physical exam demonstrated jaundice with scleral icterus with mild periumbilical tenderness to palpation without hepatosplenomegaly or ascites. Labs demonstrated elevated total bilirubin of 10.2 mg/dL with Alkaline phosphatase, ALT, and AST being 924 U/L, 429 U/L, and 279 U/L, respectively. Imaging studies including CT abdomen and pelvis with contrast, abdominal ultrasound, MRCP, and portal vein doppler were negative. Additional work up for underlying liver disease including acetaminophen and ethanol levels, SARS-CoV2, Hepatitis panel, EBV antigen, and urine toxicology were negative. It was determined patient had bupivacaine induced hepatotoxicity. Patient's health improved with conservative management and she was discharged with instructions for close monitoring of her LFTs. Discussion(s): Bupivacaine is an amino-amide anesthetic which binds to the intracellular portion of voltage-gated sodium channels and prevents depolarization of pain signals. It is metabolized by the liver and thus reports of hepatotoxicity, although rare, occur in patients with underlying liver pathology. Our patient became symptomatic with acute rise in LFTs. An extensive workup for other etiologies of acute liver toxicity was negative. Rapid vascular uptake of the drug is the most common reason for bupivacaine toxicity;and this remains a possibility for the mechanism of toxicity in our patient. A prior case report of bupivacaine hepatotoxicity demonstrated a cholestatic pattern, which is consistent with our findings.

Global Pattern of kdr-Type Alleles in Musca domestica (L.).

Purpose of Review: Houseflies, Musca domestica L., are an important sanitary pest that affects human and domesticated animals. They are mechanical carriers of more than 100 human and animal diseases including protozoan, bacterial, helminthic, and viral infections. Recently, it was demonstrated that houseflies acquired, harbored, and transmitted SARS-CoV-2 (COVID-19) for up to 1 day post-exposure. The most widely used control strategy relays on the application of pyrethroid insecticides due to their effectiveness, low mammalian toxicity, low cost, and environmental safety. The main mechanism of action of pyrethroids is to exert their toxic effects through affecting the voltage-sensitive sodium channel (VSSC) modifying the transmission of the nerve impulse and leading to the death of the insects. Target site insensitivity of the VSSC is due to the presence of single nuclear polymorphisms (SNPs) named knockdown mutations (kdr). In this review, we synthetize recent data on the type and distribution of these mutations globally. Recent Findings: Housefly resistance is reported in several countries. Increased applications of pyrethroids to control housefly populations led to the emergence of multiple evolutionary origins of resistance determined by five amino acid substitutions or specific mutations in the VSSC: kdr (L1014F), kdr-his (L1014H), super-kdr (M918T + L1014F), type N (D600N + M918T + L1014F), and 1B (T929I + L1014F). According to the global map obtained, high levels of resistance to pyrethroids are associated with the L1014F mutation found mostly in North America, Europe, and Asia, while the super-kdr mutation was mostly found in the American continent. The level of protection conferred by these alleles against pyrethroids was generally kdr-his < kdr < Type N ≤ super-kdr ≤ 1B. The relative fitness of the alleles under laboratory conditions was susceptible ≅ kdr-his > kdr > super-kdr suggesting that the fitness cost of an allele was relative to the presence of other alleles in a population and that the reversion of resistance in a free insecticide environment might be quite variable from one region to another. Summary: An adequate integrated pest management program should consider monitoring susceptibility to pyrethroids to detect early levels of resistance and predict the spread and evolution of resistant phenotypes and genotypes. From this review, the pyrethroid resistance status of housefly population was determined in very few countries and has evolved independently in different areas of the world affecting chemical control programs.