ALP-poisoned Patients Research Articles

Prognostic values of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in the early prediction of aluminum phosphide-poisoned patients’ outcomes

Background In Egypt, aluminum phosphide (ALP) is one of the most serious health problems that threaten the health system, with a very high mortality rate that ranges from 30%–100% of cases, according to medical facilities. ALP records suicidal deaths related to the toxin ingestion in Egypt, which accounts for 70% of the deaths. Patients usually deteriorate early; death is expected in the first 48 h. The aim of this study is to investigate the early recorded neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in anticipation of the ALP-intoxicated patients’ outcome. Patients and methods Thirty-three subjects diagnosed with ALP poisoning were divided into two groups according to their need for mechanical ventilation and whether they could survive or not. A complete blood count (CBC) was done immediately after admission, and NLR and PLR were calculated. Patients’ conditions were evaluated by arterial blood gases (ABG), random blood sugar (RBS), sodium (Na+), potassium (K+), and an electrocardiogram (ECG). Results There were significant differences in the need for ICU and mechanical ventilation between the different NLR groups. There was also a highly significant difference in the patient’s fate. Increased NLR was associated with a high incidence of mechanical ventilation and death in ALP-poisoned patients. Conclusion The early assessment of NLR can be valuable in predicting death and the need for ICU admission. NLR ≥ 3.35 can predict death in ALP-poisoned patients. Early CBC and calculation of NLR are promising tools that are easy and more accurate than the presence of leukocytosis or leucopenia.

The therapeutic effect of a novel parenteral formulation of dihydroxyacetone in aluminum phosphide-intoxicated patients

Background and objectivesAluminum phosphide (AlP), known as “rice tablet,” is widely used as an effective pesticide. However, AlP poisoning is a common cause of mortality in many countries, such as Iran. Unfortunately, there is no specific antidote for AlP toxicity to date. AlP releases phosphine gas when it is exposed to moisture or acid. Phosphine is a potent mitochondrial toxin that could significantly inhibit cellular energy metabolism. AlP poisoning is an emergency condition that needs instant and effective intervention. Dihydroxyacetone (DHA) is a simple saccharide used for several pharmacological as well as cosmetic purposes. Previously, we found that DHA could significantly prevent mitochondrial impairment induced by toxic agents such as cyanide and phosphine in various in vitro and in vivo experimental models. MethodsHospitalized patients (n = 111) were evaluated for eligibility criteria. Among these patients, n = 35 cases were excluded due to incomplete data (n = 11) and suspicion of poisoning with poisons other than AlP (n = 24). Meanwhile, n = 76 cases with confirmed AlP poisoning were included in the study. AlP-poisoned patients who did not receive DHA (n = 18) were used as the control group.Patients (n = 58) received at least one dose of DHA (500 ml of 5 % DHA solution w/v, i.v.) as an adjuvant therapy in addition to the routine treatment of AlP poisoning. Arterial blood gas (ABG), blood pH, bicarbonate levels, and other vital signs and biochemical measurements were monitored. Moreover, the mortality rate and hospitalization time were evaluated in DHA-treated and AlP-poisoned patients without DHA administration. Several biomarkers were assessed before (upon hospitalization) and after DHA treatment. The routine tests for AlP-poisoned patients in this study were the measurement of electrolytes (K+ and Na+), WBC, RBC, hemoglobin, INR, carbonate (HCO3), blood pH, PaCO2, and PaO2 and SGPT, SGOT, BUN, Cr. ResultsUpon patients' admission, significant decreases in blood pH (acidosis), blood PaO2, and HCO3 levels were the hallmarks of AlP poisoning. It was found that DHA significantly alleviated biomarkers of AlP poisoning and tremendously enhanced patients’ survival rate (65.52 % in DHA-treated vs 33.34 % in the control group) compared to patients treated based on hospital routine AlP poisoning protocols (no DHA). No significant adverse effects were evident in DHA-treated patients in the current study. Interpretation and conclusionsThese data suggest that parenteral DHA is a novel and effective antidote against AlP poisoning to be used as an adjuvant in addition to routine supportive treatment. Trial registrationIR.SUMS.REC.1394.102.

The Role of Echocardiographic Findings in Estimating Survival Probability of Intensive Care Unit Admitted Aluminum Phosphide Poisoned Patients.

Cardiotoxicity represents the primary cause of death in acute aluminum phosphide (AlP) poisoning. Prompt supportive care can improve patient survival. This study assessed the role of echocardiography in estimating the survival probability of AlP-poisoned patients admitted to the intensive care unit. A prospective cohort study ofsymptomatic acute AlP poisoned patientswas conductedbetween September 2019 and December 2020. Patients were subjected to history taking, clinical examination, To be included,patient evaluation needed to includeelectrocardiographic (ECG) and echocardiographic studies. The statistical analysis assessed the association between patient survival and relevant factors. Survival analysis was performed using the Kaplan-Meier survival curve and Cox proportional hazard regression. A total of 90 patients met inclusion criteria.Electrocardiographic abnormalities were detected in 38.1% of survivors and 82.6% of non-survivors (p < 0.001). Survivors had a higher mean left ventricle ejection fraction (LVEF) (50.86 ± 6.30% vs. 26.52 ± 7.64%, respectively, p < 0.001) and a lower percentage of global LV hypokinesia (4.8% vs. 94.2%, p < 0.001). The mean survival time was higher among patients with LVEF ≥ 50% than those with LVEF = 41-49% and ≤ 40% (p = 0.014 and 0.001, respectively). The hazard of death was 4.42 and 5.40 times greater in patients with LVEF ≤ 40% or with global LV hypokinesia, respectively. Regression revealed that the global LV hypokinesia, ECG abnormalities, and decreased LVEF and oxygen saturation were significantly associated with the risk of death (hazard ratios: 4.382, 3.348, 0.957, and 0.971, respectively). Echocardiography represents a valuable diagnostic tool to assess cardiac function in acute AlP poisoning. Both LVEF and global LV hypokinesia significantly impact the survival of AlP-poisoned patients. Echocardiography was superior to ECG changes in terms of accuracy for the prediction of mortality.

Modification of the hemodynamic and molecular features of phosphine, a potent mitochondrial toxicant in the heart, by cannabidiol

Aluminum phosphide (AlP) poisoning is common in many countries responsible for high mortality. The heart is the main target organ in AlP poisoning. Several studies have reported the beneficial effects of cannabidiol (CBD) in reducing heart injuries. This study aimed to investigate the possible protective effect of CBD on cardiac toxicity caused by AlP poisoning. Study groups included almond oil, normal saline, sole CBD (100 µg/kg), AlP (11.5 mg/kg), and four groups of AlP + CBD (following AlP gavage, CBD administrated at doses of 5, 25, 50, and 100 μg/kg via intravenous (iv) injection). Thirty minutes after AlP treatment, an electronic cardiovascular device (PowerLab) was used to record electrocardiographic (ECG) changes, heart rate (HR), and blood pressure (BP) for three hours. Cardiac tissue was examined for the activities of mitochondrial complexes, ADP/ATP ratio, the release of cytochrome C, mitochondrial membrane potential (MMP), apoptosis, oxidative stress parameter, and cardiac biomarkers at 12 and 24 hours time points. AlP administration caused abnormal ECG, decreased HR, and BP. AlP also significantly reduced mitochondrial complex I and IV activity and ADP/ATP ratio. The level of cytochrome C release, apoptosis, oxidative stress, and cardiac biomarkers was considerably increased by AlP, which was compensated following CBD administration. CBD was able to improve hemodynamic function to some extent in AlP poisoned rats. CBD restored ATP levels and mitochondrial function and decreased oxidative damage and thus, prevented the heart cells from entering the apoptotic stage. Further clinical trials are needed to explore any possible benefits of CBD in AlP-poisoned patients.

The Pivotal Role Of Coconut Oil Or Liquid Paraffin As Antidote Effective In Reducing Acute Aluminum Phosphide Poisoning In Cardiogenic Shock

Abstract Introduction/Objective Aluminum phosphide (Alp) is a self-poisoning agent for raising the mortality rates in developing countries. Alp is known as “Rice-tablet” which is a cheap solid fumigant pesticide that is used for grain preservation which becomes a common mode of suicidal attempts in the rural community in Egypt. This study aims to identify the mechanism of salient features and management strategies were carried out on acute Alp-poisoned patients at Poison-Emergency-Unit, ElBehira-Hospitals. That was performed between Jan2018-Jun2019. Methods Patients were subjected to a full history evaluation of age, sex, Blood gases, and ECG, were demonstrated. Patients were grouped according to their outcome into survivors and non-survivors groups. Results The results demonstrated that (93%) of Alp-poisoning cases by oral-ingestion as suicidal attempts which were (54%) survived while (46%) non-survived. The blood-gases were showed that over 50% of the cases had metabolic acidosis with a highly-significant difference between survivors and non-survivors. PH and HCO3 values were significantly lower in non-survivors than those in the survivor group. Furthermore, SaO2 value was significantly higher in survivors than that of non-survivors. So the managing Alp-poisoning should be started for first 6hr since exposure. Treatment includes early gastric lavage with potassium-permanganate-(1:10,000), sodium-bicarbonate or coconut-oil/liquid-paraffin. The mechanism of Alp-poisoning explained that, phosphine gas inhibits 70% of mitochondrial cytochrome-c-oxidase in myocardial-tissue by the effect of free-radicals; electrolyte disturbance, and intracellular acidosis all cause a reduction in cardiac function, and multi-organ damage. These effects may cause arrhythmia and myocarditis which may be the cause of death. Conclusion It was concluded that myocardial depression with shock and metabolic acidosis may lead to respiratory failure due to acute Alp-poisoning. This case study reported that coconut oil play a pivotal role in managing acute Alp- poisoning even 6h post ingestion for reducing the oxidative outcomes of phosphine and recommended as antidote for acute Alp-intoxication.

Assessment of Intravenous Lipid Emulsion as an Adjuvant Therapy in Acute Aluminum Phosphide Poisoning: A randomized Controlled Trial

Abstract Background In Egypt, Aluminium phosphide (ALP) poisoning is a major cause of suicidal deaths. Nevertheless, no efficient antidote has been found so far. Intravenous lipid emulsion (ILE) has been successfully used in resuscitation of two ALP-poisoned patients. Aim was to evaluate efficacy and safety of ILE as an adjuvant therapy of acute ALP poisoning. Methods ALP-poisoned patients were recruited from Tanta University Poison Control center. Eligible patients were randomly allocated into experimental and control groups (25 patients each). Patients in the experimental group have received ILE 20% at a rate of 10ml/h continuous IV infusion, in addition to the standard treatment. Whereas, the control group have only administered the standard treatment. Results The mortality rate in the experimental group was non-significantly lower than the control group (56% versus 76% respectively). The need for intubation and mechanical ventilation was significantly lower in the experimental group compared to the control group (36% versus 92% respectively). Moreover, the median length of hospital stay was significantly lower in survivors of the experimental group. Conclusion Adjuvant ILE use along with the supportive treatment could have a therapeutic effect in ALP poisoned patients. Additionally, it was an overall safe therapy.

Clinical Data, Laboratory Investigations and Electrocardiographic Changes as Predictors of Mortality in Acute Aluminum Phosphide Poisoning

Aluminum phosphide (AlP) is one of the fumigants which is widely used in Egypt. Limited data is available on the predictors of mortality in ALP poisoned patients. So, the aim of this work was to evaluate the role of clinical data, laboratory investigations and ECG findings in predicting mortality in these cases. A cohort retrospective study was conducted on 113 cases of ALP poisoning admitted to Tanta Poison Control Unit. History, clinical data and results of laboratory investigations were recruited. Seventy seven cases died. There was a significant difference between survivors and non- survivors as regards mode of poisoning, GCS, vital signs (except the heart rate), the presence of ECG abnormalities, pH, HCo3, K and creatine level and white blood cell count. The multivariate analysis logistic regression revealed that the presence of ECG changes and the pH level are the only independent variables that can predict mortality. Analysis of receiver operating curve of blood pH level revealed a good area under the curve (AUC) of 0.881. At a cut off value of ≤7.28 the blood pH level had a sensitivity of 71.43. It was concluded that ALP poisoning causes high mortality rate. Mortality could be predicted by ECG changes and the blood pH level. At a cut off value of ≤7.28 the blood pH level was able to predict mortality. Assessment of ECG and blood pH is highly recommended in cases of ALP poisoning for early prediction of mortality.

Prognostic value of cortisol and thyroid function tests in poisoned patients admitted to toxicology ICU

Prognostic value of cortisol and thyroid function tests (TFTs) has previously been evaluated in medical ICUs. We aimed to evaluate prognostic efficacy of cortisol and TFTs in critically ill poisoned patients admitted to toxicology intensive care unit (ICU). In a prospective study of consecutively enrolled subjects admitted to the toxicology ICU, lab analyses included TFTs (total T3 and T4 as well as TSH) and cortisol levels drawn between 8 am-10 am during period of the first 24 hours post-ingestion/exposure. Simplified Acute Physiology Score II (SAPS II) and Acute Physiology and Chronic Health Evaluation II (APACHE II) were recorded. All scores were compared to detect the best prognostic factor. Type of poisoning was also included. In 200 patients evaluated, 129 were male and mean age was 31 years. In general, SAPS II, T4, and cortisol could prognosticate death. After regression analysis, only cortisol had such efficacy (P=0.04; OR=1.06; 95%CI=1.05-1.08; cut-off=42 µg/dL; sensitivity=70%; specificity=82%). Between aluminium phosphide (ALP)- and non ALP-poisoned patients, level of consciousness, mean arterial pressure, and cortisol level could prognosticate death in ALP poisoning (all Ps<0.001 in both uni and multivariate analyses). Median (interquartile range; IQR) GCS was 7 (6, 10) and 15 (8, 15) in non-ALP and ALP-poisoned patients (P<0.003). SAPS II and APACHE II could not prognosticate death at all. Cortisol best prognosticated outcomes for subjects admitted to the toxicology ICU. Its level is higher in ALP-poisoned patients probably due to the higher stress while they remain conscious till the final stages of toxicity and are aware of deterioration of their clinical condition or may be due to their significantly lower blood pressures.

Evaluation of Various Scoring Systems in Prediction of Acute Aluminum Phosphide (ALP) Poisoning Outcome

Introduction: Aluminum phosphide (Alp) poisoning is a major health problem developing countries because of the high rates of morbidity and mortality even in well-equipped and experienced hospitals.. The aim of this study: Was to evaluate various scoring system (Acute Physiology and Chronic Health Evaluation (APACHE) score, Rapid Emergency Medicine Score (REMS), The Sequential Organ Failure Assessment (SOFA) score) at admission for outcome prediction in acute aluminum phosphide poisoned patients. Patients and methods: The present study is a cohort study that was carried out on acute Alp poisoned patients at Poison Control Unit, Tanta University Emergency Hospital. It was composed of two periods; one year retrospective (from April 2015 to March 2016) and six months prospective (from April 2016 to September 2016).All admitted patients over 16 years with acute aluminum phosphide poisoning were included in this study. Patients were grouped according to their outcome into survivors and non survivors. From the collected data, APACHE II, SOFA and REMS scores were calculated for every patient. Results: The present study was carried out on admitted fifty acute Alp poisoned patients. Out of them, survivors represented 44% and 56% were non-survivors. The majority of patients were in the age group 16-20 years, females, student, from rural areas (90%) and most of patients had ingested phosphides intentionally in a median dosage of one tablet. Hypotension, tachypnea, metabolic acidosis, hyperglycemia and higher serum creatinine levels and alanine transaminase (ALT) at admission, were risk factors of mortality from Alp. Non survivors had significantly higher APACHE II, SOFA and REMS score values than survivors. SOFA score had the best AUC (0.989) followed by APACHE II score then REMS score (0.987 and 0.970 respectively). However, no significant differences between AUC values of compared scores could be demonstrated. Conclusion: The clinical scores (APACHE II, SOFA and REMS) were similar and effective tools for determination of the severity of acute Alp poisoning. However, REMS proved to be more applicable than other scores owing to its simplicity, less time-consuming and effectiveness in emergency situations. Therefore, REMS score is suggested to be used in the emergency situations to predict outcome in Alp poisoned patients.

Inhibition of glucose-6-phosphate dehydrogenase protects hepatocytes from aluminum phosphide-induced toxicity

Aluminum phosphide (AlP) poisoning is a severe toxicity with 30–70% mortality rate. However, several case reports presented AlP-poisoned patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and extensive hemolysis who survived the toxicity. This brought to our mind that maybe G6PD deficiency could protect the patients from severe fatal poisoning by this pesticide. In this research, we investigated the protective effect of 6-aminonicotinamide (6-AN)- as a well-established inhibitor of the NADP+- dependent enzyme 6-phosphogluconate dehydrogenase- on isolated rat hepatocytes in AlP poisoning. Hepatocytes were isolated by collagenase perfusion method and incubated into three different flasks: control, AlP, and 6-AN+ALP. Cellar parameters such as cell viability, reactive oxygen species (ROS) formation, mitochondria membrane potential collapse (MMP), lysosomal integrity, content of reduced (GSH) and oxidized glutathione (GSSG) and lipid peroxidation were assayed at intervals. All analyzed cellular parameters significantly decreased in the third group (6-AN+AlP) compared to the second group (AlP), showing the fact that G6PD deficiency induced by 6-AN had a significant protective effect on the hepatocytes. It was concluded that G6PD deficiency significantly reduced the hepatotoxicity of AlP. Future drugs with the power to induce such deficiency may be promising in treatment of AlP poisoning.

Therapeutic role of hyperinsulinemia/euglycemia in aluminum phosphide poisoning

Background:Different protocols have been suggested to treat aluminum phosphide (ALP) poisoning. We aimed to evaluate the possible therapeutic effect of hyperinsulinemia/euglycemia (HIE) in treatment of ALP poisoning.Methods:In a prospective interventional study, a total of 88 ALP-poisoned patients were included and assigned into HIE group undergoing glucose/insulin/potassium (GIK) protocol and a control group that was managed by routine conventional treatments. The 2 groups were then compared regarding the signs and symptoms of toxicity and their progression, development of complications, and final outcome to detect the possible effect of GIK protocol on the patients’ course of toxicity and outcome.Results:The 2 groups were similar in terms of demographic characteristics and on-arrival vital signs and lab tests. Using GIK protocol resulted in significantly longer hospital stays (24 vs 60 hours; P < 0.001) and better outcomes (72.7% vs 50% mortality; P = 0.03). Regression analysis showed that GIK duration was an independent variable that could prognosticate mortality (odds ratio [95% confidence interval] = 1.045 [1.004,1.087]). The risk of mortality decreased by 4.5% each hour after initiation of GIK.Conclusion:GIK protocol improves the outcome of ALP poisoning and increases the length of hospital stay.

Response to “Blood Levels of Methemoglobin in Patients with Aluminum Phosphide Poisoning and its Correlation with Patient’s Outcome”

Dear Editor, I read with interest the study conducted by Mostafazadeh and colleagues regarding the blood levels of methemoglobin in patients with aluminum phosphide poisoning and its correlation with patient’s outcome published in your journal [1]. In this study, the authors have shown for the first time that in almost all aluminum phosphide (AlP)-poisoned patients, methemoglobinemia is present in some degrees with an association between the blood level of methemoglobin and mortality. Two major points should not be missed about this study; firstly, there is no doubt that AlP poisoning itself can cause symptomatic methemoglobinemia as two previously performed studies have already shown this [2, 3]. However, as you know, potassium permanganate is a strong hemolytic and oxidizing agent that can induce hemolysis and methemoglobinemia [4, 5]. The issue of possible permanganate-induced methemoglobinemia due to gastric lavage by the recommended concentration of this agent (1:10,000) is a matter of debate that warrants further studies in this regard. However, it should be mentioned that from the three previously performed studies on the methemoglobinemia due to AlP intoxication, gastro-intestinal decontamination with potassium permanganate had been performed in one of them [2, 3, 6]. In the present study, as the authors have themselves declared, gastric lavage with potassium permanganate has been done for all of the patients [1]. Of course, it should not be forgotten that the efficacy of the suggested diluted potassium permanganate for the gastrointestinal decontamination of AlP-poisoned patients has not yet been proven [7]. If gastric lavage with potassium permanganate can really cause methemoglobinemia, certainly, its risk will overweigh its benefit. Secondly, as the authors have mentioned, some researchers have shown that there is no association between AlP-ingested dose and mortality rate [8]. In addition to the accidental and/or intentional errors in reporting the number of the ingested tablets by the patients or their family members suggested by the authors, this may be due to the ingestion of exposed tablets which have lower phosphine content. When someone ingests these exposed tablets, or dissolves the exposed or non-exposed tablets in water before ingestion, less phosphine will be released in the gut resulting in a less severe toxicity and decreased rate of mortality. The first point has previously been pointed out and illustrated by two other authors [9, 10]. Also, if the patient vomits immediately after the ingestion due to the unpleasant taste and odor of the tablet, he/she will possibly survive [3, 11, 12]. Thanks for this interesting study.

Blood Levels of Methemoglobin in Patients with Aluminum Phosphide Poisoning and its Correlation with Patient’s Outcome

Although methemoglobinemia following aluminum phosphide (AlP) intoxication has been reported, probable effect of blood level of methemoglobin (Met-Hb) on outcome of AlP-poisoned patients has not yet been investigated. This study aimed to evaluate blood levels of methemoglobin in patients with AP intoxication and its correlation with patient's outcome. This prospective study was carried out at the Loghman-Hakim poison hospital from April 2009 to August 2009. All patients aged >12 years who had ingested AlP and were admitted at the hospital were enrolled in the study. Using the co-oximetry, blood Met-Hb level was measured at the time of admission and 24 h later if the patient survived. Forty-eight patients with AlP intoxication including 24 males were evaluated. Mean age of the patients was 25.5±9.5 years. There was significant association between blood level of Met-Hb at the time of admission and mortality (2.4%±7.1% in survivors versus 15.2%±13.5% in non-survivors, P<0.001). The same association was found at the 2nd day of admission (2.9%±8.2% in survivors versus 26.5%±9.9% in non-survivors, P=0.02). The present study found an association between blood level of Met-Hb and mortality in patients with AlP intoxication. Effect of administration of vitamin C and methylene blue on outcome of patients with AlP intoxication should be investigated in future studies.

Cytochrome-C Oxidase Inhibition in 26 Aluminum Phosphide Poisoned Patients

Introduction. Aluminum phosphide (ALP) is used worldwide to fumigate grain. ALP poisoning, though reported from different parts of world, is most common in north, northwest and central India. In the presence of moisture, ALP liberates phosphine, which is highly toxic. The mechanism of action of phosphine is not known though experimental studies show that it inhibits cytochrome-c oxidase leading to inhibition of mitochondrial oxidative phosphorylation. Patients and Methods. We estimated cytochrome-c oxidase activity in platelets of patients who had ingested ALP and compared them with those in healthy controls and in patients with shock due to other causes (cardiogenic shock, septic shock and hemorrhagic shock). Results. After analysis of variance using Kruskal-Wallis test followed by Mann Whitney U test, significant inhibition of cytochrome-c oxidase activity could be found in ALP-poisoned patients compared to healthy controls (z = −5.513, p < 0.001) and in patients with shock due to other causes (z = −2.344; p < 0.05). There was no significant difference in inhibition in those who survived ALP poisoning compared to those who died from ALP poisoning (t = 0.02768; p > 0.05). Conclusion. Though inhibition of cytochrome-c oxidase in platelets does not have prognostic value, it suggests that interruption of mitochondrial oxidative phosphorylation as a result of cytochrome-c oxidase inhibition may lead to multi-organ dysfunction and therapeutic strategies to maintain enzyme activity may help in managing these patients.