Problems with the effectiveness of L-carnitine and paraffin oil in acute aluminum phosphide poisoning

We have enthusiastically read the article by Abdelhamid et al. entitled “Comparing the effectiveness of L-carnitine and paraffin oil in acute aluminum phosphide poisoning using predictive biomarkers and scores: A randomized controlled clinical trial”. ¹ As this type of poisoning also frequently occurs in our region, the proposed new solutions for treating phosphide poisoning can be very important and practical. The authors presented some useful data about prognostic factors of Aluminum phosphide poisoning and suggestive new treatments.

Prescribing L-Carnitine, liquid Paraffin oil, sodium bicarbonate, and N-acetylcysteine (NAC) are among the most important practical treatments mentioned in this article. As also mentioned in the article, methods of gastric decontamination have shown contradictory results in various studies. ¹ Usually, vegetable oils like olive oil generally do not have an effect on this type of poisoning. ² The administered oils prevents the reaction between phosphide and water or acid, However, after a while, if the mixture of oil and phosphide remains in the gastrointestinal tract, the oil is either absorbed or excreted and the remaining phosphide is converted into phosphine, or phosphine and phosphide dissolve in the oil, aiding in the delayed absorption of phosphine gas in the body.^2,3 However, the recommended paraffin oil in that article ¹ also has another mechanism. In addition to preventing the release of phosphine gas, liquid paraffin oil also promotes the excretion of phosphide (unchanged) from the body through decreasing GI transit time and increasing rectal evacuation. Paraffin oil surrounds the aluminum phosphide (ALP) tablet and acts as a potent gastrointestinal (GI) evacuant, but without causing dangerous diarrhea. ¹ Paraffin oil, seemingly due to its prevention of increased phosphine gas production, leads to an elevation in cytochrome-c oxidase levels and the absence of an increase in caspase-3 levels as well. ¹ Therefore, in cases where oil administration is necessary, it appears that, as mentioned in that article, ¹ the optimal choice of oil is paraffin oil.

In the Abdelhamid et al. article, the hypothetical mechanism of action of Acetyl-L-Carnitine's (ALCAR) was not clearly explained in the introduction and methodology sections during the study's design as a potential antioxidant and anti-apoptotic factor. However, upon completing the study and administering the drug to patients, these effects were confirmed based on the obtained results. ¹ Additionally, their studied patients received an intravenous (IV) infusion of nine ampoules (9 gm) of ALCAR added to 500 mL of 0.9% normal saline in a continuous manner until improvement or death, ¹ but the article does not provide information about the infusion rate of 9 g of ALCAR; the average length of hospitalization for patients was approximately 40 h, and some patients were discharged or died sooner or later. However, the article does not specify how the dosing regimen was adjusted to ensure that all patients received a total of 9 vials of ALCAR before improvement or death.

Based on the view point of the authors of “Comparing the effectiveness of L-carnitine and paraffin oil in acute aluminum phosphide poisoning using predictive biomarkers and scores: a randomized controlled clinical trial” article, ¹ and other various studies, ⁴ it has been mentioned that prescribing NAC improves the prognosis of phosphide poisoning. Therefore, in addition to the 21-h infusion of NAC, it seems more logical to continue daily NAC infusion until the patient's condition stabilizes.

In the Abdelhamid study, ¹ aspiration of gastric contents through a nasogastric tube and administration of a mixture of normal saline 0.9% and NaHCO3 solution 8.4% were performed if the delay time was less than 2 h, on the other hand all patients presented within the 2–5 h after ALP tablet ingestion. Due to this time frame, these patients did not undergo procedures such as aspiration of gastric content and gastric lavage with normal saline plus NaHCO3. However, patients in group three underwent aspiration of gastric content and were administered 250 mL of liquid paraffin oil. Ultimately, these patients in group three had a better prognosis. ¹ This indicates the presence of phosphide and phosphine in the stomach even up to 5 h after ALP tablet ingestion. Therefore, based on this study, it seems advisable to perform gastric content aspiration, gastric lavage, and liquid paraffin oil administration for at least up to 5 h (3.3 ± 1.7 h) after ALP tablet ingestion, even for patients presenting later.

As mentioned in the Abdelhamid study, ¹ acidosis and acidemia are factors influencing the prognosis of ALP poisoning. Therefore, determining the sodium bicarbonate dose, the method of administration, the duration of administration, and the therapeutic goal of using sodium bicarbonate are essential for appropriate management of these patients. By employing a standardized and clear protocol, it is possible to prevent bias during treatment in different research groups.

In the Abdelhamid study, ¹ it is mentioned that in cases of severe and resistant pulmonary edema and/or metabolic acidosis resulting from ALP poisoning, dialysis is conducted. However, considering the mechanism of pulmonary edema and acidosis in this type of poisoning, hemodialysis might not be feasible concurrently due to severe hypotension. If possible, Continuous Renal Replacement Therapy (CRRT) would be preferable over regular hemodialysis. ⁵

In the Abdelhamid study, ¹ the Group 3 (NAC + Par group) was further divided into two subgroups: (1) Patients whose gastric content was aspirated and then paraffin oil was administered, and (2) Patients who received only paraffin oil without gastric content aspiration; However, the results section of the study does not provide a breakdown of outcomes for these two subgroups, and it is not clear which of these two subgroups had better survival. Answering this question could be pivotal for guiding further research studies.

According to the results recorded in the Abdelhamid study, ¹ patients in the control group had lower Glasgow Coma Scale (GCS) scores, higher Sequential Organ Failure Assessment (SOFA) scores, and higher anion gap metabolic acidosis (severe high anion gap metabolic acidosis) based on laboratory tests and clinical status upon admission. Additionally, this group of patients had higher levels of blood urea nitrogen (BUN) upon admission, which could indicate a catabolic state or dehydration. As the article also mentions, GCS and SOFA scores are strong predictors of survival in acutely AlP-poisoned patients. Therefore, the higher mortality rate in the control group might be due to their worse clinical status upon admission. Further studies are indeed necessary to delve into these aspects.

Certainly, as know, a SOFA score below 9 often corresponds to an ICU mortality rate of less than 30%. ⁶ Considering the results of SOFA score in each group and the mortality rates among the three groups, ¹ it can be inferred that at least in ALP poisoning, the mortality rate is significantly higher than what would be predicted based on the calculated SOFA score percentage. Further analysis is needed to understand this disparity between the expected mortality based on the SOFA score and the actual observed mortality in patients with ALP poisoning.

Indeed, the use of the Simplified Acute Physiology Score (SAPS) II calculator to predict hospital mortality might require further investigation, especially considering the observed mortality rates in patients poisoned with ALP in the study of Abdelhamid et al. ¹ The disparity between the predicted mortality using SAPS II and the actual mortality rates observed suggests that the validity of SAPS II in these patients needs to be explored through additional research and analysis.

Considering all the aforementioned factors, it appears that the treatment of patients poisoned with ALP goes beyond just supportive care ¹ and includes on-time aggressive symptomatic and supportive treatment. ⁷