RٌRT for poisoning Dr. Osama El Shahat

1. Dr. Osama El-Shahat
Consultant Nephrologist
Head of Nephrology Department
New Mansoura General Hospital (international)
ISN Educational Ambassador

2. Criteria for consideration of RRT in poisoning .
RRT modality
Volume distribution of the poisoning.
Management of specific toxic medication ingestions
Conclusion
Objectives

3. Indications for RRT
Renal Indications
Life-threatening indications
Hyperkalemia
Metabolic Acidosis
Pulmonary edema
Uremic complications
Non Renal Indications
Fluid removal in congestive
heart failure& Fluid
management in multiorgan
failure
Cytokine manipulation in
sepsis
Treatment of drug overdose
Nutrition support

4. Renal Replacement Therapy(RRT)
for poisoning
Will it work?
What’s the best technique?
Who need it ?

5. 1. Progressive deterioration despite intensive supportive therapy.
2. Severe intoxication with depression of midbrain function
leading to hypoventilation, hypothermia and hypotension.
3. Development of complication of coma, such as pneumonia or
septicemia, and underlying conditions predisposing to such
complications (e.g. "obstructive air way disease).
Criteria for consideration of dialysis
or hemoperfusion in poisoning

6. 4. Impairment of normal drug excretory function in the
presence of hepatic or renal insufficiency.
5. Intoxication with agents with metabolic and /or delayed
effects, e.g. methanol, ethylene glycol , and paraquat.
6. Intoxication with an extractable drug or poison, which
can be removed at a rate exceeding endogenous
elimination by liver or kidney .
Criteria for consideration of dialysis
or hemoperfusion in poisoning

7. Choice of therapy

8. What’s the best technique ??
 Peritoneal dialysis
 Hemodialysis
 Plasma pharesis
 Hemoperfusion
 Continuous hemodiafiltration (CRRT)

9. Rarely performed unless
 It’s the only available
method
 Hemodialysis is difficult to
institute quickly, such as in
small children
Peritoneal dialysis (PD)

10.  Theoretically useful if drug is:
 water soluble
 small (MW <500)
 not highly protein bound
 not so bad ,you don’t mind waiting . . . TOO SLOW
 Not very effective, being 1/8 to 1/4 as efficient as
hemodialysis
Peritoneal dialysis (PD)

12.  Best if drug is:
 water-soluble
 low molecular weight
 not highly protein bound
Hemodialysis

16. More effective than HD in
 Protein-bound drugs
 Lipid-soluble drugs
If a drug is equally well removed by HD
and HP, hemodialysis is preferred
Hemoperfusion
1. Potential problems of cartridge saturation
2. Treat coexisting acid–base disturbances

18. Continuous hemodiafiltration

22. Acute poisoning with certain
mushrooms or with other strongly
protein-bound poisons such as
parathion or paraquat may require
emergency plasmapheresis
depending on the severity of the
intoxication.
plasmapheresis

23. High-flux or high-efficiency HD should always be considered the
first line of treatment if the patient tolerates this therapy.
High-flux or high-efficiency HD followed by convective mode of
CRRT should be considered in the setting of a large-volume of
distribution intoxicant.
As opposed to the setting of AKI ,if dialysis is needed to treat
an acute intoxication, the dialysate or replacement bath
needs to have the therapeutic levels of phosphorous and
potassium in order to avoid electrolyte disturbances,

24.  Volume of distribution:
 is the drug accessible?
 how big a volume to clear?
 Clearance (CL):
 CL = flow rate x extraction ratio
 does the method efficiently
cleanse the blood?
Will it work?

25. Importance of volume of
distribution

26.  The volume of distribution (VD) is the theoretical
volume into which a drug is distributed
 Some drugs will have VD values exceeding the
volume of total body water (0.6 L/kg) because
they are extensively bound to, or stored in, tissue
sites
Importance of volume of distribution

27. Volume of distribution (Vd)
 A calculated number - not real
= amt. of drug / plasma conc.
= mg/kg / mg/L = L/kg
 Total body water = 0.6 L/kg
 ECF = 0.25 L/kg
 Blood or plasma = 0.07 L/kg

28.  The amount of drug present in the blood
represents only
 a small fraction of the total body load
 Additional drug will enter the blood from tissue
stores, sometimes causing a “rebound” of the toxic
manifestations

29. Large Vd:
 Opioids
 Tricyclics
 Digoxin
 Camphor
 Phencyclidine
 Phenothiazines
 Glutethimide
Vd for some common drugs
Small Vd:
 Alcohols
 Lithium
 Phenobarbital
 Phenytoin
 Salicylate
 Valproic acid

30. Modality Selection

31. Drug Serum Conc. mg/L Method of choice
Phenobarbital 100 HP>HD
Glutethimide 30-40 HP
Methaqualone 40 HP
Salicylates 80 HD
Theophylline 40 HP>HD
Paraquat 0.1 HP>HD
Methanol 500 HD
Trichloromethanol 500 HP>HD
Meprobamate 100 HP
Serum Concentrations of Common Poisons in Excess of
Which hemodialysis or hemoperfusion Should Be
Considered

32. Modality Selection
 haemodynamically unstable -> CRRT
 increased ICP -> CRRT
 severe volume overload -> CRRT (can remove 200-
300mL/hr or even more)
 mechanical ventilation –> CRRT
 high protein turnover/ catabolic patients -> CRRT
 hyperkalaemia -> intermittent therapy (IHD) better and
faster
•Kellum, J. A., et al (2010) “Continuous Renal Replacement Therapy” Oxford University Press, pages – pages 33-37

33. Przegląd Lekarski 2013

34. Przegląd Lekarski 2013

35. Acute ingestion:
Mild : ingestions of less than 150 mg/kg.
Moderate: ingestions of 150-300 mg/kg.
Severe : with overdoses of 300-500 mg/kg.
Salicylates (Aspirin) overdose
Chronicingestion:
Due to intake of more than 100 mg/kg/day over a period of several
days and usually occurs in elderly patients with chronic
underlying illness.

36. Symptoms:
Severe intoxications are associated with lethargy;
convulsions, and coma, which may result from
cerebral edema.
Salicylates (Aspirin) overdose (cont.)
Noncardiogenic pulmonary edema occurs in up to
30% of adults and is more common with chronic
ingestion.

37.  Gastric lavage if presentation is within 1 hour of ingestion.
 Administer activated charcoal.
 Alkaline diuresis
 Hemodialysis is indicated for blood levels in excess of 80
mg/dl after acute intoxication
 May be useful with chronic toxicity when levels are as
low as 40 mg/dl if other indications of dialysis exist.
 Among these are refractory acidosis, severe CNS
depression, progressive clinical deterioration
 Pulmonary edema and renal failure.
Treatment of Salicylates overdose

38. Methanol
IHD
RRT should be continued
until the serum methanol
concentration is < 25 mg/dL
and the anion-gap metabolic
acidosis and osmolal gap are
normal. Rebound may occur
up to 36 hours
•Kellum, J. A., et al (2010) “Continuous Renal Replacement Therapy” Oxford University Press, pages – pages 33-37
Management of specific toxic medication ingestion
Lithium
IHD
IHD removes lithium
faster but rebound is a
significant problem and
can be addressed
effectively with CRRT

39. Theophylline
IHD/CRRT/ hemoperfusion
RRT should be continued
until clinical improvement
and a plasma level < 20
mg/L is obtained; rebound
may occur
Valproic acid
IHD/CRRT/ hemoperfusion
At supratherapeutic drug
level , plasma proteins
become saturated, and the
fraction of unbound drug
increases substantially and
becomes dialyzable
•Kellum, J. A., et al (2010) “Continuous Renal Replacement Therapy” Oxford University Press, pages – pages 33-37
Management of specific toxic medication ingestion

40. Management of specific toxic medication ingestion
Metformin
Metformin use is becoming more common as the obesity
rate in the USA goes up.
Metformin intoxication in some patients can cause an acute
lactic acidosis.
Metformin is eliminated naturally through the GI tract, is poorly
protein bound and has a mild volume of distribution.
Metformin overdose can be treated easily with standard or high-
flux HD as a way to correct the lactic acidosis as well as to
remove the medication .
Timothy E. etal.:,Management of toxic ingestions with the use of renal replacement
therapy Pediatr Nephrol (2011) 26:535–541

41. Management of specific toxic medication ingestion
Vancomycin
Vancomycin is a commonly used medication for the treatment of
Gram-positive infections. It has a large molecular weight and
relatively large volume of distribution, and it is highly protein
bound. Vancomycin essentially acts as a double compartment
system with an intravascular and extravascular component,
respectively.
Timothy E. etal.:,Management of toxic ingestions with the use of renal replacement
therapy Pediatr Nephrol (2011) 26:535–541

42. Management of specific toxic medication ingestion
Vancomycin
More recently, the combination of high-flux HD and CRRT
has been found to successfully decrease acute vancomycin
Levels . It is possible to wait for the tissue levels to
pass into the vascular space and upon rebound, repeat the
HD procedure. Alternatively, sequential therapy of HD
followed by convective clearance with high-flow CRRT
(as a way to prevent secondary rebound and for elimination)
may be used.
Timothy E. etal.:,Management of toxic ingestions with the use of renal replacement
therapy Pediatr Nephrol (2011) 26:535–541

43.  Recognition of poisoning and drug toxicity require
high index of suspicion and careful clinical
evaluation.
 Multiple drugs overdose is common.
 RRT to be consider in drug toxicity according to
special criteria and drug distribution
Conclusion

44. ‫السموم‬ ‫اكز‬‫ر‬‫م‬
‫بالمنصورة‬ ‫السموم‬ ‫مركز‬
‫العنوان‬:‫المعهد‬ ‫شارع‬ ‫المنصورة‬
‫أمام‬ ‫جيهان‬ ‫من‬ ‫المتفرع‬ ‫الصحي‬
‫ومقابل‬ ‫الطوارئ‬ ‫مستشفى‬
‫البولية‬ ‫المسالك‬ ‫عيادات‬
‫تليفون‬:0502376762
‫شمس‬ ‫عين‬ ‫جامعه‬ ‫مستشفى‬
‫التخصصى‬-‫السموم‬ ‫مركز‬
‫العنوان‬:-‫شارع‬‫رمسيس‬-
‫عباسية‬-‫القاهره‬-‫مصر‬
‫تليفون‬:-0224823314
Thank you

47. Thank you

48.  In the retrospective study we described the
diagnostics and treatment of 163 patients with above
mentioned acute poisonings and acute renal failure
in whom we used all current available therapeutic
conservative methods, renal replacement therapy
and other extracorporeal elimination methods which
we had the possibility to use from 1967 to 2003 in our
dialysis centre.
Conclusion

49. Continuous renal replacement therapy and charcoal
plasmaperfusion in treatment of amanita mushroom poisoning.
 Abstract
 Hemoperfusion has been used in the treatment of mushroom poisoning for many
years. The aim of this study was to study the efficacy of charcoal plasmaperfusion
(CPP) and continuous renal replacement therapy (CRRT) in 2 patients severely
poisoned by the amanita mushroom. Both patients arrived at the ICU from another
hospital with a diagnosis of amanita phalloides mushroom poisoning. The patients
were precociously treated with CRRT for 20 h and CPP for 3 h every day. The
treatments were effected for 3 and 5 days, respectively. Both patients recovered
completely and were discharged asyntomatic after 7 and 10 days
Splendiani G1, Zazzaro D, Di Pietrantonio P, Delfino L.
Author information .

50.  Methanol is highly toxic, producing metabolic acidosis,
blindness, and death.
 Evidence of metabolism and/or symptoms may be
delayed for 18 to 24 hours.
 is related to the degree of acidosis and thus the time
Toxicity between exposure and specific treatment.
Methanol Poisoning

51.  Prognosis is poor in patients with coma or seizure and
severe metabolic acidosis (pH <7).
 Toxic exposure may occur by ingestion, inhalation, or
dermal routes.
Methanol Poisoning (cont.)

52. Preferred MethodDrug
Carbamazepine HP
Ethylene glycol HD
Lithium HD
Methanol HD
Methotrexate HF
Phenobarbital HP
Procainamide HF
Salicylate HD or HP
Theophylline HP or HD
Valproic acid HD or HP

53. LABORATORY / MONITORING
 Obtain CBC, electrolytes, urinalysis, and ABG.
 A wide anion gap metabolic acidosis suggests the possibility of
methanol overdose.
 Obtain serum methanol and ethanol levels.
An elevated osmolal gap suggests methanol poisoning
but a normal osmolal gap does NOT reliably exclude
methanol poisoning.
Methanol Poisoning (cont.)

54. Treatment
 Do not induce emesis.
 gastric lavage if the patient is seen less than 1 hour after ingestion.
cotraindicated with compromised airway
or decreased level of consciousness.
 Give folinic acid 1 mg/kg IV (maximum 50 mg); followed by folic
acid, 1 mg/kg q4h for six doses.
Methanol Poisoning (cont.)

55. Treatment
 Fomepizole; an alcohol dehydrogenase antagonist (FDA approved ).
The dosage is 15 mg/kg IV followed by 10 mg/kg IV q12h for four doses.
 Ethanol delays metabolism of Methanol to its toxic metabolites
 Hemodialysis indications :
Blood methanol level > 50 mg/dl
Severe metabolic acidosis
Renal failure
Methanol Poisoning (cont.)

56. Severity of salicylate intoxication

57. ‫السموم‬ ‫اكز‬‫ر‬‫م‬
(‫بالمنصورة‬ ‫السموم‬ ‫مركز‬
‫العنوان‬:‫المعهد‬ ‫شارع‬ ‫المنصورة‬
‫أمام‬ ‫جيهان‬ ‫من‬ ‫المتفرع‬ ‫الصحي‬
‫ومقابل‬ ‫الطوارئ‬ ‫مستشفى‬
‫البولية‬ ‫المسالك‬ ‫عيادات‬
‫تليفون‬:2376762
‫شمس‬ ‫عين‬ ‫جامعه‬ ‫مستشفى‬
‫التخصصى‬-‫السموم‬ ‫مركز‬
‫العنوان‬:-‫شارع‬‫رمسيس‬-
‫عباسية‬-‫القاهره‬-‫مصر‬
‫تليفون‬:-02-24823314

58.  Administer 100 mEq of sodium bicarbonate in 1000
ml D5W at a rate of 10-15 ml/kg/hour if the patient is
clinically volume depleted until urine flow is
achieved.
 Maintain alkalinization using the same solution at 2-3
ml/kg/hour,
Treatment of Salicylates overdose (cont.)

59.  monitor urine output, urine pH (target pH, 7-8), and serum
potassium.
 Achievement of alkaline diuresis often requires the simultaneous
administration of at least 20 mEq/L potassium chloride.
 Hemodialysis is indicated for blood levels in excess of 100-130 mg/dl
after acute intoxication.
Treatment of Salicylates overdose (cont.)

60.  Hemodialysis may be useful with chronic toxicity when
levels are as low as 40 mg/dl if other indications of
dialysis exist.
 Among these are refractory acidosis, severe CNS
depression, progressive clinical eterioration
 Pulmonary edema and renal failure.
Treatment of Salicylates overdose (cont.)

61. Laboratory data :
Prothrombin time prolongation is common.
 ABGs may reveal an early respiratory
alkalosis, followed by metabolic acidosis.
 Approximately 20% of patients exhibit either respiratory
alkalosis or metabolic acidosis alone.
 Hypoglycemia, common in children, is rare in adults.
Salicylates (Aspirin) overdose (cont.)

62.  Blood levels must be drawn 6 hours or more after acute ingestion of
salicylates .
 Levels in excess of 70 mg/dl at any time represent moderate to
severe intoxication;
 levels of more than 100 mg/dl are very serious and often fatal.
 Bicarbonate levels and pH are more useful than salicylate levels as
prognostic indicators in chronic intoxication.
Salicylates (Aspirin) overdose (cont.)

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