|Year : 2020 | Volume
| Issue : 4 | Page : 250-254
Hemoperfusion in the management of acute poisoning
C Mahesh, N Nagalakshmi, Karanam Sivaparvathi, RD Nagaraj, N Praveen, N Raja Amarendra, B Maria, B Alekhya, Sivakumar Vishnubothla
Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
|Date of Submission||09-Sep-2019|
|Date of Acceptance||25-Nov-2019|
|Date of Web Publication||6-Jan-2021|
Dr. Karanam Sivaparvathi
Assistant professor, Department of Nephrology, SVIMS, Tirupati, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
The role of extracorporeal therapies for poisoning is expanding in the present days with technological advances and increased awareness among physicians attending critically ill patients both intensivists and nephrologists. In this regard we present our experience on hemoperfusion in poisonings over a period of 5 years. A total of 6 patients were treated with hemoperfusion during this period with majority of them were due to antiepileptic drugs (phenytoin, phenobarbitone, carbamazepine) followed by paraquat (a weedicide).The age range is from 19-59 years with a mean age of 31.3 years and male: female ratio of 1:1. Coming to the clinical presentation, 3 of them presented with unconsciousness, one with altered sensorium and two of them with vomiting associated with oliguria and breathlessness. Five of the six (83.3%) required ventilatory support during the hospital stay. The total number of hemoperfusion sessions required was 10, with an average of 1.6 sessions per patient. The average number of hemodialysis sessions required was 2.3 sessions per patient. Only one patient developed procedure related complication of thrombocytopenia related oral bleeding which subsided with supportive therapy and no further hemoperfusion. Four out of six patients (66.6 %) recovered while 33.4 % expired and both the patients who expired consumed paraquat poisoning. In conclusion hemoperfusion has a significant role in the management of certain poisonings which would reduce the morbidity and mortality associated with these poisonings.
Keywords: Extracorporeal therapies, hemoperfusion, management of acute poisonings
|How to cite this article:|
Mahesh C, Nagalakshmi N, Sivaparvathi K, Nagaraj R D, Praveen N, Amarendra N R, Maria B, Alekhya B, Vishnubothla S. Hemoperfusion in the management of acute poisoning. J NTR Univ Health Sci 2020;9:250-4
|How to cite this URL:|
Mahesh C, Nagalakshmi N, Sivaparvathi K, Nagaraj R D, Praveen N, Amarendra N R, Maria B, Alekhya B, Vishnubothla S. Hemoperfusion in the management of acute poisoning. J NTR Univ Health Sci [serial online] 2020 [cited 2021 Apr 23];9:250-4. Available from: https://www.jdrntruhs.org/text.asp?2020/9/4/250/306132
| Introduction|| |
The mortality and morbidity secondary to poisonings is a major social and economic challenge. Its ethology, treatment modalities, and outcomes vary across the geographic regions and countries. There are several routes of poisoning including oral, inhalational, external skin exposure. After ingestion patients present with acute organ dysfunction and in many cases, the poison is unknown at least initially and, in these instances, after general supportive treatment to preserve the vital organ functions, the patients are grouped in to various toxidromes based on the clinical signs and symptoms which helps in management. The most common toxidromes include anticholinergic, cholinergic, adrenergic, GABAergic, sodium and potassium channel blocker related, serotonergic and opiate related.
The management of a poisoned patient is a two-pronged approach which involves identification of the nature of poison at the earliest to institute specific therapy and attend the multi organ systems failure accurately for a better outcome. The various methods employed to limit the toxicity include (1) To limit the further absorption (detoxification) and (2) enhance elimination. The various methods of detoxification include gastric lavage, emesis, use of activated charcoal; however, all of these should not be used in those patients whose airways are not secured.
Extracorporeal therapies are one of the methods to enhance elimination which would give gratifying results if used in a timely manner. They are based on the principles of diffusion, convection or adsorption and the various techniques includes hemodialysis, hemofiltration, hemodiafiltration, therapeutic plasmapheresis, and hemoperfusion. The most common extracorporeal modality used was hemodialysis and it is best for the toxins with small molecular weight (less than 2000 Daltons), high water solubility, low protein binding (<50%) and small volume of distribution (0.75- <1 liter/kg) however it is ineffective for drugs/toxins with high molecular size, high protein binding and high lipid solubility in which there is a significant role for hemoperfusion.
| Hemoperfusion|| |
In hemoperfusion blood perfuses a column containing of either activated charcoal or synthetic anion exchange resin. Protein bound substances bind to the adsorptive column and are removed from circulation. The hemoperfusion was more effective and less limited by protein binding than hemodialysis especially for poisons for which antidotes were unavailable, such as barbiturates and paraquat.
Procedure of hemoperfusion is similar to hemodialysis, except here blood passes through a cartridge containing sorbent [Figure 1]. It can be done with either HD or CRRT machine. It is usually done for a 4 hours after which the sorbent gets saturated and extraction ratios of toxins and efficiency decreases. It cannot be reused. It removes particles ranging from 100 to 40,000 Daltons. The hemoperfusion cartridge has a huge surface area (1000 m2/gram of sorbent) and it is said that one teaspoonful of activated charcoal has about the same surface area of a football court, hence the extraction ratios with hemoperfusion would be phenomenally higher compared to hemodialysis (e.g. extraction ration of theophylline with hemoperfusion is 99% while it is 50% with hemodialysis).
Vascular access is usually a femoral venous catheter or an internal jugular vein catheter and may require higher to normal heparin dose for anticoagulation.
The complications associated with hemoperfusion include thrombocytopenia, leucopenia, hypocalcemia, hypophosphatemia, hypoglycemia, and a decrease in fibrinogen. These are due to nonspecific adsorption of biologic components to column; however, it is overcome with coating of the cartridge with biocompatible membranes and sometimes antibiotics also to extend its use in sepsis. Other disadvantages include high cost and unavailability of the cartridge with ease.
Hemoperfusion is still applicable in poisons that cannot be treated satisfactorily in other ways like theophylline, phenytoin, phenobarbital, carbamazepine, paraquat, and glutethemide.
Keeping in view of the importance of extracorporeal therapies in the acute management of poisoning patients we present our experience of 6 patients with poisoning and treatment with hemoperfusion and hemodialysis [Table 1].
| Case Reports|| |
A 21-year-old female, was a known epileptic on carbamazepine 200 mg three times daily and clobazam 10 mg at night, presented to casualty in comatose condition, with a history of consumption of carbamazepine around 30–40 tablets, at 3 pm and arrived to hospital at 8 pm, on presentation her blood pressure (BP) was 100/60 mm hg (millimeters of mercury), pulse rate (PR) 96 beats per minute, respiratory rate (RR) was 32/minute, GCS (Glasgow coma scale) E1V1M1 and SPO2 on room air was 84%, has metabolic acidosis, patient was intubated in view of her hypoxia and comatose state, serum drug levels of carbamazepine was sent and it was reported as more than 20 mcg/ml. The normal reference range of the lab was 4–11 mcg/ml. Patient has prolonged QRS complex on electrocardiograph and received sodium bicarbonate as well as inotrope support for the hypotension. Patient was started on hemoperfusion and after one session of hemoperfusion serum drug levels became 12.3 mcg/ml and patients consciousness improved and required three sessions of hemodialysis to correct metabolic acidosis, though patient did not have renal dysfunction and the final drug level at discharge was 2 mcg/ml. Patient was extubated after 5 days and discharged home with normal renal function.
A 25-year-old female, a known epileptic on phenytoin 100 mg three times daily, presented with history of consumption of 15–20 tablets of eptoin (phenytoin), a cumulative dose of 1.5–2 gm of phenytoin with features of drowsiness, nystagmus, and ataxia, GCS on admission was E4V 2 M5, BP was 110/70 mm hg, PR 9 beats per min, RR 20/min and serum phenytoin levels were 39.6 mcg/ml (normal therapeutic concentrations of phenytoin were 10–20 mcg/ml) with metabolic acidosis in ABG (arterial blood gas analysis). Underwent one cycle of hemoperfusion and 2 cycles of hemodialysis, discharged after 11 days and discharge phenytoin levels were less than 2.5 mcg/ml.
A 59-year-old male, diabetic and hypertensive since 15 years, was on phenytoin 100 mg three times daily for seizures secondary to neurocysticercosis, presented with history of consumption of 25 tablets of phenytoin each 100 mg and drowsiness with poor respiratory effort to casualty. His BP was 140/80 mm hg, PR 96/min, RR 12/min GCS was E1V1M1, was intubated and supported with inotropes for hypotension which he developed during the hospital course and serum phenytoin levels were more than 40 mcg/ml, received two sessions of hemoperfusion each lasting for 3 hours and 2 sessions of hemodialysis, patient was extubated after 24 hours, discharged in stable condition.
A 30-year-old male presented to casualty with history of consumption of phenobarbital around 100 tablets of 60 mg each with vomiting and loss of consciousness. On admission BP was 120/80 mm hg, PR 88/min, RR 18/min. GCS E1V1M1, was intubated and on investigations his serum phenobarbital levels was >80 mcg/ml (normal range 15-44 mcg/ml). He received 1 session of hemoperfusion and 3 sessions of hemodialysis and discharged with normal sensorium.
A 28-year-old male presented with history of consumption of paraquat of unknown quantity and after 4 days with complaints of vomiting and decreased urine output with normal sensorium, BP at presentation 140/90 mm hg, PR 98/min, RR 20/min. on investigations serum creatinine was 11.8 mg/dl with metabolic acidosis, since the serum estimation of paraquat levels was not available with us, patient was started on hemoperfusion and hemodialysis sequentially and after receiving 2 sessions of hemoperfusion and hemodialysis, patient also required ventilatory support due to development of hypoxia during the hospital stay. Patient left the hospital against medical advice and on further enquiry was found to have expired after 1 week.
A 19-year-old female presented to emergency with history of consumption of paraquat and complaints of vomiting and breathlessness and normal sensorium with stable vital parameters and on evaluation patient has renal dysfunction, serum creatinine 2.9 mg/dl, with hypoxia and mild metabolic acidosis, patient underwent 3 sessions of hemoperfusion and 2 sessions of hemodialysis and was intubated for hypoxia during the hospital stay, and expired after 7 days of hospitalization.
Results: we have observed overall 6 patients of poisonings who required treatment with hemoperfusion with or without hemodialysis during a period of 56 months (January 2014–August 2019). Only one of them has diabetes and hypertension of 15 years duration as comorbidities. Among them 33.3% were due to pesticides (paraquat), while rest of them 66.7% were due to anti-epileptic drugs. In the clinical presentation, 3 of them presented with unconsciousness, one with altered sensorium and two of them with vomiting associated with oliguria and breathlessness. Five of the six (83.3%) required ventilatory support during the hospital stay. The total number of hemoperfusion sessions required was 10, with an average of 1.6 sessions per patient. The average number of hemodialysis sessions required was 2.3 sessions per patient. Only one patient developed complication of thrombocytopenia related oral bleeding which subsided with supportive therapy and no further hemoperfusion. Four out of six patients (66.6%) recovered while 33.4% expired and both the patients who consumed paraquat poison were expired.
| Discussion|| |
In our experience we have observed most of the poisonings were secondary to anti-epileptic drugs (AED) followed by herbicide paraquat. The most common AED was phenytoin, followed by carbamazepine and phenobarbital. Toxicokinetic represents a unique expansion of pharmacokinetics describing the impact of toxins on normal body drug interactions and a proper understanding of the toxicokinetic profile helps in appropriate choosing of the extracorporeal modality; however, any extracorporeal technique only removes the substances that are distributed in the intravascular compartment, as the volume of distribution increases the effectives of extracorporeal therapies comes down. Phenytoin acts by blocking voltage sensitive sodium channels in neurons and prevents the electrical spread of a focus of irritable tissue from entering normal tissue. Phenytoin toxicity is very common due to its narrow therapeutic index. Clinical features of phenytoin toxicity include nystagmus, ataxia, confusion, in severe cases seizures and coma. The therapeutic plasma concentration was 10–20 mcg/ml, it is metabolized by hepatic enzyme and excreted by kidney. More than 90% of phenytoin is protein bound with very less free fraction and its molecular weight is 272 Daltons and volume of distribution is 0.7 l/kg, so charcoal hemoperfusion was advantageous for effective removal of drug due to its high protein binding capacity., The same was evident in two of our patients.
Carbamazepine is an iminostilbene derivative used mostly for complex partial seizures, trigeminal neuralgia and glossopharyngeal neuralgias. Acts by blocking presynaptic voltage gated sodium channels, as well as NMDA and adenosine receptors. Intoxication usually produces altered mental status ranging from drowsiness to coma and or cardiac abnormalities like, prolongation of QRS interval, sinus tachycardia, ventricular tachycardia, and hypotension. The therapeutic concentration ranges from 4 to 12 mcg/ml. Our patient also presented with coma and serum levels were >20 mcg/ml and patient also had cardiac manifestations in the form of prolongation of QRS interval hypotension treated with inotrope support. High protein binding (80-85%), large volume of distribution (1–2 l/kg) favor the use of initial hemoperfusion for carbamazepine intoxication and literature shows that use of hemodialysis along with hemoperfusion would give the best clearance and less side effects associated with hemoperfusion.
Phenobarbital poisoning is rarely encountered now days because of use of benzodiazepines in place of phenobarbital, they act by binding to GABA a receptors. It has a narrow therapeutic index of 10–30 mg/ml. Its overdose can cause CNS depression, respiratory failure with hemodynamic instability. Because of the prolonged half-life of 5 days, these patients tend to be in prolonged coma. Our patient also presented in coma with phenobarbitone levels >80 mg/ml, hemoperfusion is superior to hemodialysis, as it is effective in removing highly protein bound substances and phenobarbital is 40–60% protein bound, which is evident in our patient.
Paraquat (1,1'- dimethyl-4,4 'dipyridilium) is a widely available herbicide associated with fatal toxicity. It is actively taken up against concentration gradient into lung tissue leading to pneumonitis, and lung failure. It also causes renal and liver injury. It is effectively removed by hemoperfusion. Both of our patients had renal dysfunction and required hemoperfusion and hemodialysis to correct the associated metabolic abnormalities and renal failure; however, both of them succumbed to death, as was the high reported mortality in paraquat poisoning.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to b'e reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
| Conclusion|| |
In conclusion hemoperfusion has an invaluable role in the management of certain poisonings like paraquat, phenytoin, carbamazepine, phenobarbitone as has been evidenced by our presentation and needs to be considered as appropriate to reduce the morbidity and mortality associated with these acute poisonings.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ronco C, Bellomo R, Kellum JA, Ricci Z. Critical Care Nephrology E-Book. Elsevier Health Sciences; 2017.
Kumar PP, Lingappa L, Shah MA, Shaikh FA. Charcoal hemoperfusion for phenytoin intoxication. Indian Pediatr 2012;49:152-3.
Anseeuw K, Mowry JB, Burdmann EA, Ghannoum M, Hoffman RS, Gosselin S, et al
. Extracorporeal treatment in phenytoin poisoning: Systematic review and recommendations from the EXTRIP (Extracorporeal Treatments in Poisoning) Workgroup. Am J Kidney Dis 2016;67:187-97.
Vallianou N, Giannopoulou M, Trigkidis K, Bei E, Margellou E, Apostolou T. A case of severe carbamazepine overdose treated successfully with combined hemoperfusion and hemodialysis technique. Saudi J Kidney Dis Transpl 2017;28:906-8.
] [Full text]
Lindberg MC, Cunningham A, Lindberg NH. Acute phenobarbital intoxication. South Med J 1992;85:803-7.
Mohammed Ebid AHI, Abdel-Rahman HM. Pharmacokinetics of phenobarbital during certain enhanced elimination modalities to evaluate their clinical efficacy in management of drug overdose. Ther Drug Monit 2001;23:209-16.
Hsu CW, Lin JL, Lin-Tan DT, Chen KH, Yen TH, Wu MS, et al
. Early hemoperfusion may improve survival of severely paraquat-poisoned patients. PloS One 2012;7:e48397.