CRRT Versus Plasmapheresis in Aluminum Phosphide Poisoning

Aluminum phosphide (AlP) is a solid fumigant pesticide sold as tablets in use since the 1940s. It is considered to be an ideal pesticide because of its cheapness, efficiency, and easy availability in the market and is widely used as a grain preservative worldwide.The mortality in cases of aluminum phosphide poisoning varies between 60% and 90%, even in experienced and well-equipped hospitals. Patients mostly die due to cardiovascular collapse, refractory shock, severe acidemia, fulminant hepatic failure, and or adult respiratory distress syndrome.

Continuous renal replacement therapy (CRRT) is a slow and smooth continuous extracorporeal blood purification, which is designed to replicate depurative function of the kidney. It is usually implemented over 24 h to several days with an aim of gentle correction of fluid overload and removal of excess uremic toxins. Furthermore, many observational studies considered CRRT as the predominant form of RRT in the intensive care unit (ICU) for critically ill patients with AKI and/or multiorgan failure, along with acute brain injury or other causes of increased intracranial pressure or generalized brain edema. The effectiveness of CRRT is mainly due to its accurate volume control, steady acid-base and electrolyte correction, and achievement of hemodynamic stability in adults and pediatrics.

Plasmapheresis (PPH) can rapidly and effectively remove toxic substances and their potentially toxic metabolites from the blood compartment, especially those with high protein-binding. As the potential benefit of therapeutic plasma exchange is increasingly recognized, its use is becoming more widespread, and case reports have confirmed its value in the treatment of drug overdose. The application of plasmapheresis dramatically reversed the severe biochemical and clinical manifestations and was able to prevent serious co-occurrence.

Seventy five (75) patients will be included in this study. They will be randomly allocated into three groups (25 patients \| each)

1. Control Group (C Group): routine management.
2. CRRT Group: routine management + CRRT.
3. PPH Group: routine management + PPH.

Immediately after ICU admission:

All Patients will receive the routine management including:

* Care for airway, breathing and circulation.
* Intravenous fluids guided by central venous pressure measurement and vasopressors (Norepinephrine) IV infusion will be used to treat hypotension and refractory shock, intubation and mechanical ventilation in the following conditions: apnea, respiratory failure, hypoxia, inadequate ventilation, disruption of airway reflexes, disturbed conscious level (GCS \<8).
* Phosphine excretion can be increased by maintaining adequate hydration and renal perfusion with intravenous fluids and low dose dopamine (4-6 μg/kg/min). Diuretics like furosemide can be given if systolic blood pressure is \>90 mm Hg to enhance excretion as the main route of elimination of phosphine is renal.
* Correction of metabolic acidosis by intravenous sodium bicarbonate will also be considered in a dose of 50-100 mEq intravenously every 8 hour till the bicarbonate level rises to 18-20 mEq/L.
* Additionally, magnesium sulfate: 1g IV infusion every 1hr for the first 3 hrs, followed by 1-1.5 g every 6 hrs for 24 hrs was administered.
* Decontamination will be done by gastric lavage using normal saline mixed with sodium bicarbonate solution (2 ampoules sodium bicarbonate 25% added to each 500cc saline) in all Patients presented within 2 hrs of toxic ingestion. Then, a single (50 gm) dose of activated charcoal will be administered.

Then patients will receive either CRRT or PPH after confirmation of exposure to aluminum phosphide.

Peri-interventional evaluation: -

1. Time elapsed between exposure and start of management.
2. Standard vital signs (ABP, HR, Spo2, ETCO2). ECG and GCS are continuously monitored and documented.
3. Laboratory studies:

   1. Phosphine gas level in blood by gas chromatography: on admission and another sample after CRRT or PPH
   2. Tropnin levels immediately on admission and at the end of CRRT or PPH.
   3. ABG to assess acid base status and lactate levels. Basic sample on admission and serial samples every 2 hours after the start of CRRT or PPH for follow up, evaluation and assessment.

Prisma-flex (Gambro-Swedan) machine will be used to carry out both CRRT and PPH sessions. Each CRRT session continue for 72 hours, while PPH session continue for 4 hours. The need for another session will be evaluated by the SBP\< 90 mmHg, lactate level \>1mmol, acid base status; PH\<7.35 and renal function; S. creatinine\>2.

All participating patients will be observed until discharge from the hospital or death. Continuous monitoring and documentation of their vital signs, oxygen saturation, and conscious level will be done.

Parameters to be evaluated regularly

1. Laboratory studies

   * CBC, Coagulation profile (PT, PC, INR) if within normal, reassessment after 48 hours.
   * Liver function tests LFTs if within normal, reassessment after 48 hours.
   * Urea and creatinine will be assessed daily.
   * Troponin T and I if within normal, reassessment after 48 hours.
   * Blood glucose/ 4 hours for the first 48 hours then every 8 hours.
   * K, Mg, Ca will be assessed daily.
2. Standard monitoring: ABP, HR, Spo2, ETCO2 and ECG continuously.
3. 24 hours total urine output (UOP).

Eligibility Criteria:
Inclusion Criteria:

* Patients exposed to AlP poisoning of either sex.
* Critically ill with severe symptomatic acute AlP poisoning; SBP\<90mmHg, PH\<7.32 and HR\<60 bpm.
* Age \>18 year.

Exclusion Criteria:

* Refusal to consent participating research.
* Age \<18 years.