Management of critically Ill COVID-19 patients: Exploring the potential of morphine and assessing disadvantages of acetaminophen

Abstract: Caspian J Intern Med 2025 (Spring); 16(2): 381-383 Morphine for COVID-19 management 381 Caspian J Intern Med 2025 (Spring); 16(2): 381-383 DOI: 10.22088/cjim.16.2.381 Letter to Editor Management of critically Ill COVID-19 patients: Exploring the potential of morphine and assessing disadvantages of acetaminophen Dear Editor As the COVID-19 pandemic has become a significant challenge to healthcare systems worldwide, it is crucial to explore effective treatment approaches for critically ill patients. Acetaminophen has often been administered as the first-line medication for pain relief and fever reduction in COVID-19 patients, with little consideration given to its potential toxicities. However, high doses of acetaminophen in critically ill COVID-19 patients can pose certain disadvantages (1). Firstly, acetaminophen has limited anti-inflammatory properties, which may be a concern considering the prominent role of inflammation in COVID-19 lung complications. While acetaminophen can alleviate pain and reduce fever, medications with stronger anti-inflammatory effects may be more beneficial in managing the inflammatory response associated with severe COVID-19. Secondly, acetaminophen can potentially cause liver toxicity, especially when taken in high doses or for an extended period. When absorbed from the intestine, acetaminophen is metabolized in the liver cells through two major pathways: glucuronidation and sulfation. The majority of acetaminophen is metabolized via glucuronidation, producing a non-toxic metabolite that is eliminated in the urine. However, in cases of high-dose or prolonged acetaminophen use, when the glucuronidation pathway becomes saturated, a smaller fraction is metabolized through sulfation and another pathway called cytochrome P450 (CYP) 2E1. The CYP2E1 pathway produces a harmful protein called N-acetyl-p-benzoquinone imine (NAPQI) in the mitochondria. Under normal conditions, NAPQI is rapidly detoxified by glutathione, which neutralizes and eliminates toxic substances. However, excessive acetaminophen consumption overwhelms the available glutathione stores, resulting in the accumulation of NAPQI and subsequent hepatocyte necrosis (2). The severity of the disease is influenced not only by the acetaminophen dosage and initial liver damage but also by the inflammatory response triggered by acetaminophen-induced liver injury. During hepatocyte necrosis, damaged cells release danger-associated molecular patterns (DAMPs), which are recognized by neutrophils and resident hepatic macrophages (Kupffer cells), activating these immune cells. Activated hepatic macrophages release proinflammatory cytokines like IL-1β or TNF-α, as well as chemokines such as CCL2, further amplifying inflammation and promoting the recruitment of immune cells, including bone-marrow-derived monocytes and neutrophils, to the liver. Acetaminophen-induced liver toxicity can manifest as hepatocellular necrosis and liver failure (2, 3).On the other hand, morphine, a potent opioid analgesic, has several advantages when used in critically ill COVID-19 patients. Firstly, morphine effectively manages severe pain, which is a significant concern in critically ill patients, especially those experiencing respiratory distress or other complications. By alleviating pain, morphine improves patient comfort and enhances their ability to cooperate with necessary medical interventions. Furthermore, morphine has the potential to improve oxygenation in severe COVID-19..