Hepatotoxicity in Obese Versus Nonobese Patients With Acetaminophen Poisoning Who Are Treated With Intravenous N-Acetylcysteine

Abstract

There is limited information regarding the outcomes associated with acetaminophen (APAP) poisoning in obese individuals. It is possible that patients who are obese are more susceptible to APAP-induced liver injury, thereby diminishing the efficacy of antidotes such as N-acetylcysteine (NAC). We evaluated the outcomes associated with APAP poisoning in obese versus nonobese adults who are treated with intravenous (IV) NAC. This was a retrospective cohort study conducted in a tertiary care, academic medical center. Adult patients with APAP toxicity, who were treated with IV NAC between June 2005 and August 2012, were included. The patients were categorized into 2 groups based on their body mass index (BMI): (1) obese (BMI ≥ 30.0 kg/m) versus (2) nonobese (BMI 18.5-24.9 kg/m). The primary outcome measure was the proportion of patients who developed hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1000 IU/L). A total of 80 patients were included in the final cohort (40 in each group). The median BMI for the obese and nonobese groups was 34.5 kg/m [interquartile range (IQR) 31.4-40.2] and 22.4 kg/m (IQR 21.2-23.9), respectively (P < 0.001). Other than more white patients being present in the nonobese group, there were no other baseline differences between groups with regard to demographics, liver function tests, or coagulation studies. Obese patients received a median IV NAC dose of 291.5 mg/kg (IQR 270.8-300.7) compared with 300 mg/kg (IQR 287.8-301.9) in the nonobese group (P = 0.07). Hepatotoxicity occurred in 27.5% of the obese patients and 37.5% of the nonobese patients (P = 0.34). No adverse drug effects were noted in either group. Obese and nonobese patients being treated with IV NAC for APAP toxicity experienced similar rates of hepatotoxicity.

Being overweight or obese as a risk factor for acute liver injury secondary to acute acetaminophen overdose

“…A retrospective cohort by Radosevich in 2016 finds that obese patients (BMI > 30) has reduced incidence of hepatotoxicity (27.5%), as compared to the 37.5% from nonobese cases (BMI 18.5‐24.9). However, it is still important to note that these reported incidences are clearly higher than the 7.3% to 15.8% traditionally found in the general populations . In an animal model of obesity using overfed Spraque‐Dawley rats, the obese rats demonstrated increased acetaminophen hepatotoxicity compared with controls…”

“…Absence of association between overweight‐obesity and hepatotoxicity in our study may be explained by a few factors. Although all of our obese subjects have BMIs exceeding 30, they are relatively small (mean weight 74, maximum weight 90.0 kg) when compared with subjects from western populations where the aforementioned studies have been conducted (Varney's median weight 110, range 101‐160kg and Radosevich's mean weight 98, range 83.2‐108.9 kg) . This can serve to weaken the effect of overweight‐obesity on hepatotoxicity.…”

“…Uncovering whether being overweight or obese increases the risk of hepatotoxicity in patients with acute acetaminophen overdose has implications for the possible modification in the regimen of NAC therapy in overweight and obese populations. Currently, the dosing regimen for NAC therapy relies on actual body weight up to the weight limits of 100 and 110 kg for the intravenous and oral administration, respectively . Thus, severely obese patients who are already at increased risk of hepatotoxicity are placed at even higher risk using this cap‐dose method.…”

“…Consequently, the remaining liver cells are more susceptible to the toxic effects of acetaminophen. This poses growing concerns regarding the potential for increased hepatotoxicity in obese patients with acetaminophen overdose . However, no controlled studies have actually documented the occurrence of hepatotoxic effects from acetaminophen overdose in the obese compared to the nonobese human population.…”

Comparing the Use of Dopamine and Norepinephrine in Shock Treatment

“…Others included the period for ICU stay and the total number of days that did not need the sustenance of the organ in which the mean arterial pressure was 65 mm Hg. Besides, administration of dobutamine as well as the variable hemodynamic deviations or other agents that are inotropicwas also included [15]. The researchers placed adverse events in various categories including arrhythmias.…”