Dr. Aidah Abu El Soud Alkaissi An-Najah National University Faculty of Nursing Paracetamol...
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Transcript of Dr. Aidah Abu El Soud Alkaissi An-Najah National University Faculty of Nursing Paracetamol...
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Paracetamol intoxicationParacetamol intoxication (acetaminophen, (acetaminophen, N-N-acetyl-acetyl- p- p-
aminophenol, APAP, NAPA, 4-hydroxy-aminophenol, APAP, NAPA, 4-hydroxy-acetanilideacetanilide))
Aidah Abu El Soud Alkaissi Aidah Abu El Soud Alkaissi
RN, PhDRN, PhD
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Pharmacodynamics Pharmacodynamics
Paracetamol reduces pain and feverParacetamol reduces pain and fever
The mechanism of effect is prevention of synthesis of The mechanism of effect is prevention of synthesis of prostaglandine through inhibition of enzyme cyclooxygenesis in prostaglandine through inhibition of enzyme cyclooxygenesis in the central neural systemthe central neural system
Dosage:Dosage: Adults - 2 tablets up to 4 times a day, as needed. Do not take Adults - 2 tablets up to 4 times a day, as needed. Do not take more than every 4 hours or exceed 8 tablets (4 doses) within 24 more than every 4 hours or exceed 8 tablets (4 doses) within 24 hourshours
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
PharmacokineticsPharmacokinetics
AbsorptionAbsorption After oral application, Acetaminophen is rapidly absorbed from After oral application, Acetaminophen is rapidly absorbed from
the stomach and small intestinethe stomach and small intestine
Plasma concentration reaches its peak after 15 to 60 minutes Plasma concentration reaches its peak after 15 to 60 minutes after taking, a life half time in plasma is 1 to 4 hours after the after taking, a life half time in plasma is 1 to 4 hours after the therapy dosetherapy dose
ExtractionExtraction 98% of Paracetamol is extracted through kidneys as conjugants 98% of Paracetamol is extracted through kidneys as conjugants
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Paracetamol intoxicationParacetamol intoxicationAcetaminophen (N-acetyl-p-aminophenol)Acetaminophen (N-acetyl-p-aminophenol)
PathophysiologyPathophysiology
Is one of the most common pharmaceuticals associated with Is one of the most common pharmaceuticals associated with both intentional and accidental poisoningboth intentional and accidental poisoning
Biochemical evidence of maximal damage may not be attained Biochemical evidence of maximal damage may not be attained
until 72-96 hours after ingestion of the overdose until 72-96 hours after ingestion of the overdose
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Paracetamol intoxicationParacetamol intoxicationAcetaminophen (N-acetyl-p-aminophenol)Acetaminophen (N-acetyl-p-aminophenol)
Acetaminophen is primarily biotransformed to nontoxic products Acetaminophen is primarily biotransformed to nontoxic products
in the liver via conjugation with glucuronic acid and, to a lesser in the liver via conjugation with glucuronic acid and, to a lesser degree, sulfate, and eliminated by the kidneysdegree, sulfate, and eliminated by the kidneys
A small proportion (5-15%) of acetaminophen is metabolized A small proportion (5-15%) of acetaminophen is metabolized through the cytochrome P-450 enzyme pathway producing a highly through the cytochrome P-450 enzyme pathway producing a highly reactive and toxic metabolite, N-acetyl-para-benzoquinoneimine reactive and toxic metabolite, N-acetyl-para-benzoquinoneimine (NAPQI) which may cause hepatic injury(NAPQI) which may cause hepatic injury
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Paracetamol intoxicationParacetamol intoxicationAcetaminophen (N-acetyl-p-aminophenol)Acetaminophen (N-acetyl-p-aminophenol)
The hepatic glutathione conjugates the NAPQI to produce The hepatic glutathione conjugates the NAPQI to produce NN--acetyl-p-aminophenol (APAP) acetyl-p-aminophenol (APAP) mercapturate and APAP-cysteine mercapturate and APAP-cysteine which are both nontoxic metaboliteswhich are both nontoxic metabolites
Acetaminophen exposure becomes toxic when glucuronidation and Acetaminophen exposure becomes toxic when glucuronidation and sulfation pathways become saturated and cellular glutathione sulfation pathways become saturated and cellular glutathione stores are depletedstores are depleted
In such cases, NAPQI binds to cellular proteins and membranes, In such cases, NAPQI binds to cellular proteins and membranes, causes disruption of protein function and damage to cell causes disruption of protein function and damage to cell membranes, and leads to cell injury and death, causing membranes, and leads to cell injury and death, causing centrilobular hepatic necrosis centrilobular hepatic necrosis
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Paracetamol intoxicationParacetamol intoxicationAcetaminophen (N-acetyl-p-aminophenolAcetaminophen (N-acetyl-p-aminophenol))
Defined as a peak plasma alanine aminotransferase (ALT) activity Defined as a peak plasma alanine aminotransferase (ALT) activity exceeding 1000 IU/Lexceeding 1000 IU/L
Aspartate transaminase (AST) exceeding 1000 IU/L indicates severe Aspartate transaminase (AST) exceeding 1000 IU/L indicates severe liver damageliver damage
At risk of severe liver damage if he/she has ingested more than 150mg At risk of severe liver damage if he/she has ingested more than 150mg paracetamol/kg body weight, or, in adults, more than 12g (24 standard paracetamol/kg body weight, or, in adults, more than 12g (24 standard tablets)tablets)
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Paracetamol intoxicationParacetamol intoxicationAcetaminophen (N-acetyl-p-aminophenolAcetaminophen (N-acetyl-p-aminophenol))
Without specific antidotal therapy, 10% would suffer severe Without specific antidotal therapy, 10% would suffer severe liver damage but 1 to 2% will develop fulminant hepatic failure liver damage but 1 to 2% will develop fulminant hepatic failure and this is often fataland this is often fatal
One to 2% of patients develop acute renal failure requiring One to 2% of patients develop acute renal failure requiring dialysisdialysis
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
FrequencyFrequency
In the US: In the US: Acetaminophen is one of the most common Acetaminophen is one of the most common pharmaceutical agents involved in overdose, as reported to the pharmaceutical agents involved in overdose, as reported to the American Association of Poison Control CentersAmerican Association of Poison Control Centers
APAP toxicity is the most common cause of hepatic failure APAP toxicity is the most common cause of hepatic failure requiring liver transplantation in Great Britain and the second requiring liver transplantation in Great Britain and the second most common cause of liver failure requiring transplantation in most common cause of liver failure requiring transplantation in the United States the United States
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Clinical Assessment Amount of Clinical Assessment Amount of Ingestion Ingestion
The time of ingestion is essential for determining whether The time of ingestion is essential for determining whether antidotal therapy is required immediatelyantidotal therapy is required immediately
Clinicians should also consider the possibility of co-ingestion of Clinicians should also consider the possibility of co-ingestion of other agentsother agents
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
DiagnosisDiagnosis
blood for urgent estimation of the plasma paracetamol concentration blood for urgent estimation of the plasma paracetamol concentration after 4 hours since the time of ingestionafter 4 hours since the time of ingestion
Blood and urine toxicologic screens & a pregnancy test if the patient Blood and urine toxicologic screens & a pregnancy test if the patient is a menstruating femaleis a menstruating female
Assess whether the patient is at enhanced risk of severe liver damage Assess whether the patient is at enhanced risk of severe liver damage
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Enhanced Risk of Severe Liver DamageEnhanced Risk of Severe Liver Damage
Consume alcoholConsume alcohol
MalnourishedMalnourished
Take enzyme-inducing drugs (e.g. carbamazepine (Tegretol), Take enzyme-inducing drugs (e.g. carbamazepine (Tegretol), Anticonvulsant, antimanic agent, Phenytoin, phenobarbitone, Anticonvulsant, antimanic agent, Phenytoin, phenobarbitone, primidone, rifampicinprimidone, rifampicin
Those with conditions causing glutathione depletion (e.g. malnutrition, Those with conditions causing glutathione depletion (e.g. malnutrition, eating disorders and HIV infection) may be at risk of liver damage eating disorders and HIV infection) may be at risk of liver damage from lower plasma paracetamol concentrations than others from lower plasma paracetamol concentrations than others
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Signs and symptomsSigns and symptoms
Consciousness is not depressed unless other drugs have also Consciousness is not depressed unless other drugs have also been taken or there is a very high plasma paracetamol been taken or there is a very high plasma paracetamol concentration of the order of 6.62 mmol/l (1000 mg/l) with a concentration of the order of 6.62 mmol/l (1000 mg/l) with a metabolic acidosis metabolic acidosis
Nausea and vomiting usually develop within a few hours of Nausea and vomiting usually develop within a few hours of ingestion of a hepatotoxic dose of paracetamol ingestion of a hepatotoxic dose of paracetamol
Elevation of the plasma alanine and aspartate transaminase Elevation of the plasma alanine and aspartate transaminase activity from normal values of less than 40 to as much as 10 000 activity from normal values of less than 40 to as much as 10 000 or even 20 000 U/l caused by their release from a large mass of or even 20 000 U/l caused by their release from a large mass of necrotic hepatocytesnecrotic hepatocytes
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Signs and symptomsSigns and symptoms
With mild to moderate increases in the plasma bilirubin With mild to moderate increases in the plasma bilirubin concentration and prothrombin time ratioconcentration and prothrombin time ratio
The prolongation of the prothrombin time reflects acute The prolongation of the prothrombin time reflects acute
impairment of synthesis of the vitamin K-dependent clotting impairment of synthesis of the vitamin K-dependent clotting factorsfactors
There is little or no increase in the plasma alkaline phosphatase There is little or no increase in the plasma alkaline phosphatase activity unless liver damage is severe or the patient is a chronic activity unless liver damage is severe or the patient is a chronic alcoholicalcoholic
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Signs and symptomsSigns and symptoms
Oliguric renal failure may become apparent within 24 to 48 h after the Oliguric renal failure may become apparent within 24 to 48 h after the overdose of paracetamol, associated with back pain, microscopic overdose of paracetamol, associated with back pain, microscopic haematuria and proteinuriahaematuria and proteinuria
Fulminant hepatic failure may develop in severely poisoned patients Fulminant hepatic failure may develop in severely poisoned patients from the third to the sixth dayfrom the third to the sixth day
Characterized by deepening jaundice, encephalopathy, increased Characterized by deepening jaundice, encephalopathy, increased intracranial pressure, disordered haemostasis with disseminated intracranial pressure, disordered haemostasis with disseminated intravascular coagulation and haemorrhage, hyperventilation, acidosis, intravascular coagulation and haemorrhage, hyperventilation, acidosis, hypoglycaemia and renal failure. The prognosis is very poor hypoglycaemia and renal failure. The prognosis is very poor
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Initial Treatment of Acute Initial Treatment of Acute Acetaminophen Ingestion Acetaminophen Ingestion
Acetaminophen levels greater than Acetaminophen levels greater than 150 µg/ml150 µg/ml at four hours post at four hours post ingestion or levels above the nomogram line should be ingestion or levels above the nomogram line should be considered toxicconsidered toxic
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Management of acetaminophen ingestion Management of acetaminophen ingestion I. Gastrointestinal DecontaminationI. Gastrointestinal Decontamination
When acetaminophen is the only substance ingested, gastric When acetaminophen is the only substance ingested, gastric lavage or ipecac administration may be beneficial for large lavage or ipecac administration may be beneficial for large ingestions in patients who present within two hours of ingestioningestions in patients who present within two hours of ingestion
Ipecac is contraindicated in the setting of altered mental status, Ipecac is contraindicated in the setting of altered mental status, or a co-ingestion that potentially can cause seizures or rapid or a co-ingestion that potentially can cause seizures or rapid deterioration of mental statusdeterioration of mental status
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Management of acetaminophen ingestionManagement of acetaminophen ingestion I. Gastrointestinal DecontaminatioI. Gastrointestinal Decontaminatio
Protracted vomiting induced by ipecac may cause difficulty with Protracted vomiting induced by ipecac may cause difficulty with the subsequent administration of activated charcoal or the subsequent administration of activated charcoal or acetaminophen antidotacetaminophen antidot
Some toxicologists who feel that gastric lavage has not been Some toxicologists who feel that gastric lavage has not been proven to be helpful and should be used only if the ingestion is proven to be helpful and should be used only if the ingestion is potentially rapidly fatal and the patient presents to the potentially rapidly fatal and the patient presents to the emergency department within 1 hour of the ingestionemergency department within 1 hour of the ingestion
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Management of acetaminophen ingestion Management of acetaminophen ingestion
II. Activated charcoal administrationII. Activated charcoal administration Administration of 50g charcoal may be considered if:Administration of 50g charcoal may be considered if:
more paracetamol than 150mg/kg body weight is thought to have more paracetamol than 150mg/kg body weight is thought to have been ingestedbeen ingested
it can be given within one hour of the overdoseit can be given within one hour of the overdose
ingestion of unknown quantityingestion of unknown quantity
ingestion of 100mg/kg or more if known liver disease, anorexia, ingestion of 100mg/kg or more if known liver disease, anorexia, alcohol abuse, or on anticonvulsant or barbiturate therapyalcohol abuse, or on anticonvulsant or barbiturate therapy
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Management of acetaminophen ingestion Management of acetaminophen ingestion II. Activated charcoal administrationII. Activated charcoal administration
Those that argue against giving charcoal believe that it may decrease Those that argue against giving charcoal believe that it may decrease the bioavailability of the antidote N-acetylcysteine (NAC)the bioavailability of the antidote N-acetylcysteine (NAC)
The proponents of giving activated charcoal recommend increasing The proponents of giving activated charcoal recommend increasing the initial loading dose of NAC (140 mg/kg) by 30-40%the initial loading dose of NAC (140 mg/kg) by 30-40%
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Management of acetaminophen ingestion Management of acetaminophen ingestion II. Activated charcoal administrationII. Activated charcoal administration
Repeat doses of activated charcoal have no significant effect on Repeat doses of activated charcoal have no significant effect on acetaminophen ingestion because of its rapid absorption and acetaminophen ingestion because of its rapid absorption and limited enterohepatic excretionlimited enterohepatic excretion
Use of cathartic agents (such as sorbitol, magnesium citrate, or Use of cathartic agents (such as sorbitol, magnesium citrate, or magnesium sulfate) is common but probably does not affect magnesium sulfate) is common but probably does not affect acetaminophen absorptionacetaminophen absorption
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Management of acetaminophen ingestion Management of acetaminophen ingestion III. Antidote Therapy for Acetaminophen ToxicityIII. Antidote Therapy for Acetaminophen Toxicity
N-acetylcysteine (NAC) N-acetylcysteine (NAC)
Is the N-acetyl derivative of the protein amino acid L-cysteine Is the N-acetyl derivative of the protein amino acid L-cysteine
NAC is available as a nutritional supplement and as a drug NAC is available as a nutritional supplement and as a drug
It is given orally or by slow intravenous infusion in the treatment of It is given orally or by slow intravenous infusion in the treatment of acetaminophen overdose. acetaminophen overdose. NAC is theorized to work through a number NAC is theorized to work through a number of protective mechanismsof protective mechanisms
Early administration of NAC, within 8 hours of ingestion, is nearly Early administration of NAC, within 8 hours of ingestion, is nearly 100% hepatoprotective100% hepatoprotective
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Management of acetaminophen ingestion Management of acetaminophen ingestion III. Antidote Therapy for Acetaminophen ToxicityIII. Antidote Therapy for Acetaminophen Toxicity
N-acetylcysteine (NAC) N-acetylcysteine (NAC)
NAC is also used in the treatment of respiratory disorders, NAC is also used in the treatment of respiratory disorders, such as acute and chronic bronchitis associated with the such as acute and chronic bronchitis associated with the production of excessive or viscous mucus production of excessive or viscous mucus
For such respiratory disorders, it is delivered as an inhalantFor such respiratory disorders, it is delivered as an inhalant
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Management of acetaminophen ingestionManagement of acetaminophen ingestion III. Antidote Therapy for Acetaminophen ToxicityIII. Antidote Therapy for Acetaminophen Toxicity
N acetylcysteine (NACN acetylcysteine (NAC
NAC is a glutathione precursor that repletes glutathione storageNAC is a glutathione precursor that repletes glutathione storage
N-N-acetylcysteine may reduce the severity of liver necrosis by acetylcysteine may reduce the severity of liver necrosis by directly conjugating with and/or reducing the reactive directly conjugating with and/or reducing the reactive metabolite NAPQI (Tee et al 1986)metabolite NAPQI (Tee et al 1986)
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Management of acetaminophen ingestionManagement of acetaminophen ingestion III. Antidote Therapy for Acetaminophen ToxicityIII. Antidote Therapy for Acetaminophen Toxicity
N acetylcysteine (NACN acetylcysteine (NAC
NAC also functions as an anti-inflammatory and antioxidant and has NAC also functions as an anti-inflammatory and antioxidant and has positive inotropic effectspositive inotropic effects
NAC increases local nitric oxide concentrations, and this vasodilatory NAC increases local nitric oxide concentrations, and this vasodilatory effect on microcirculatory blood flow enhances local oxygen delivery effect on microcirculatory blood flow enhances local oxygen delivery to peripheral tissuesto peripheral tissues
These vasodilating effects decrease morbidity and mortality even in These vasodilating effects decrease morbidity and mortality even in the setting of established hepatotoxicitythe setting of established hepatotoxicity
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Efficacy of NACEfficacy of NAC
Results of the Multi-center Oral N-Acetylcysteine trial suggest that Results of the Multi-center Oral N-Acetylcysteine trial suggest that NAC is beneficial up to 24 hours after ingestionNAC is beneficial up to 24 hours after ingestion
Other studies comparing a 48-hour oral protocol in the United States Other studies comparing a 48-hour oral protocol in the United States vs. a 20-hour intravenous NAC protocol in Britain found that both vs. a 20-hour intravenous NAC protocol in Britain found that both modalities were effective if started within 8-10 hours of ingestionmodalities were effective if started within 8-10 hours of ingestion
A 72-hour oral NAC protocol appeared to be more effective for A 72-hour oral NAC protocol appeared to be more effective for high-risk patients presenting late (i.e., 16-24 hours following high-risk patients presenting late (i.e., 16-24 hours following ingestion)ingestion)
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Efficacy of NACEfficacy of NAC
Prior to the advent of an antidote, the mortality rate of patients at Prior to the advent of an antidote, the mortality rate of patients at probable risk of hepatotoxicity (> 200 µg/ml at four hours) was probable risk of hepatotoxicity (> 200 µg/ml at four hours) was reported between 5.3% and 24%reported between 5.3% and 24%
The overall mortality rates reported with the 20-hour intravenous The overall mortality rates reported with the 20-hour intravenous NAC protocol and the 72-hour oral protocol were 2% and 0.68%, NAC protocol and the 72-hour oral protocol were 2% and 0.68%, respectivelyrespectively
No fatalities were reported in any protocol in which NAC therapy No fatalities were reported in any protocol in which NAC therapy was instituted within 10 hours of ingestion was instituted within 10 hours of ingestion
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Mechanism of Action of N-acetylcysteineMechanism of Action of N-acetylcysteine
The antidote NAC is available in the United States as an oral The antidote NAC is available in the United States as an oral formform
An intravenous form is available in Canada andAn intravenous form is available in Canada and
Europe but is not yet FDA approved in the USAEurope but is not yet FDA approved in the USA
Start treatment with NAC in patients whose plasma paracetamol Start treatment with NAC in patients whose plasma paracetamol concentration related to the time from ingestion is above the concentration related to the time from ingestion is above the relevant line on the graph (Nomogram)relevant line on the graph (Nomogram)
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Nomogram For Paracetamol Poisoning. Check you are using the Nomogram For Paracetamol Poisoning. Check you are using the correct units micromols/Litrecorrect units micromols/LitreA level of over 1300 at 4 hours requires treatment (1000 for high A level of over 1300 at 4 hours requires treatment (1000 for high risk patients)risk patients)
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Timing of NAC AdministrationTiming of NAC Administration
The optimal time is within the first eight hours following The optimal time is within the first eight hours following acetaminophen ingestionacetaminophen ingestion
During this period and regardless of the amount ingested and the During this period and regardless of the amount ingested and the acetaminophen level, NAC is uniformly effectiveacetaminophen level, NAC is uniformly effective
After the eight-hour post-ingestion period, the efficacy of NAC After the eight-hour post-ingestion period, the efficacy of NAC decreases progressivelydecreases progressively
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Timing of NAC AdministrationTiming of NAC Administration
If a patient with acetaminophen overdose presents more than If a patient with acetaminophen overdose presents more than eight hours after ingestion;eight hours after ingestion;
an acetaminophen level should be sent to the lab,an acetaminophen level should be sent to the lab, NAC should be started immediately for those with suspected NAC should be started immediately for those with suspected
significant ingestions while awaiting the resultsignificant ingestions while awaiting the result
decisions regarding whether NAC therapy should be continued or decisions regarding whether NAC therapy should be continued or discontinued depend on the result of the acetaminophen leveldiscontinued depend on the result of the acetaminophen level
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
PO administrationPO administration of NAC - ADULT of NAC - ADULT
140 mg/kg140 mg/kg loading dose, loading dose,
followed by followed by 70 mg/kg70 mg/kg q4h for 17 additional doses q4h for 17 additional doses (total 1330 mg/kg over 72 h)(total 1330 mg/kg over 72 h)
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Dosage for NAC infusion - ADULTDosage for NAC infusion - ADULT
(1) (1) 150mg/kg150mg/kg IV infusion in IV infusion in 200mL 5% dextrose200mL 5% dextrose over over 15 minutes15 minutes, then, then
(2) (2) 50mg/kg50mg/kg IV infusion in IV infusion in 500mL 5% dextrose500mL 5% dextrose over over
4 hours4 hours, then, then
(3) (3) 100mg/kg100mg/kg IV infusion in IV infusion in 1000mL 5% dextrose1000mL 5% dextrose over over 16 hours16 hours
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Adverse reactions to NAC and their Adverse reactions to NAC and their managementmanagement
Adverse effects which may be localised to the area surrounding the Adverse effects which may be localised to the area surrounding the infusion site or may be more generalisedinfusion site or may be more generalised
These usually occur during the first 30 minutes of administration These usually occur during the first 30 minutes of administration when large amounts of NAC are being given rapidlywhen large amounts of NAC are being given rapidly
They include nausea, flushing, itching, erythematous rash, urticaria, They include nausea, flushing, itching, erythematous rash, urticaria, angioedema, bronchospasm and, rarely, hypotension or angioedema, bronchospasm and, rarely, hypotension or hypertensionhypertension
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Delayed NAC TherapyDelayed NAC Therapy
Recently, a randomized blinded trial from Britain evaluated the Recently, a randomized blinded trial from Britain evaluated the efficacy of late NAC therapy in patients with fulminant liver failure efficacy of late NAC therapy in patients with fulminant liver failure and Grade III or IV hepatic encephalopathyand Grade III or IV hepatic encephalopathy
The investigators demonstrated significant improvement in survival The investigators demonstrated significant improvement in survival rate (48% vs 20%) with NAC therapy and decreased incidence of rate (48% vs 20%) with NAC therapy and decreased incidence of elevated intracranial pressure and systemic hypotensionelevated intracranial pressure and systemic hypotension
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Delayed NAC TherapyDelayed NAC Therapy
In another study examining effects of NAC on the In another study examining effects of NAC on the microcirculation of different organs in patients with either microcirculation of different organs in patients with either Grade III or IV hepatic coma and fulminant liver failure from Grade III or IV hepatic coma and fulminant liver failure from different etiologies, the authors discovered that NAC different etiologies, the authors discovered that NAC increased cardiac index, decreased vascular resistance, and increased cardiac index, decreased vascular resistance, and improved oxygen delivery and extractionimproved oxygen delivery and extraction
This evidence supports NAC therapy for acetaminophen-toxic This evidence supports NAC therapy for acetaminophen-toxic patients regardless of the time of ingestion, the optimal dose patients regardless of the time of ingestion, the optimal dose and duration of late NAC therapy remains undefinedand duration of late NAC therapy remains undefined
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Hepatic NecrosisHepatic Necrosis
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Hepatic NecrosisHepatic Necrosis
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Management of acetaminophen ingestion Management of acetaminophen ingestion V. Liver TransplantV. Liver Transplant
Admit patients to an ICU setting if they show signs of significant Admit patients to an ICU setting if they show signs of significant hepatotoxicity; hepatic failure; or other potentially life-threatening, hepatotoxicity; hepatic failure; or other potentially life-threatening, coexisting, toxicologic, or medical issuescoexisting, toxicologic, or medical issues
Liver transplantation may be the last viable option in patients with Liver transplantation may be the last viable option in patients with fulminant hepatic failure from acetaminophenfulminant hepatic failure from acetaminophen
The shortcomings of this practice include deciding the optimal timing The shortcomings of this practice include deciding the optimal timing for referral and the relatively limited experience with liver for referral and the relatively limited experience with liver transplantations for acetaminophen hepatic damagetransplantations for acetaminophen hepatic damage
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing
Management of acetaminophen ingestion Management of acetaminophen ingestion V. Liver TransplantV. Liver Transplant
In a study examining liver transplant for patients with fulminant In a study examining liver transplant for patients with fulminant hepatic failure, advanced hepatic coma, severe acidosis, markedly hepatic failure, advanced hepatic coma, severe acidosis, markedly prolonged prothrombin time, and evidence of significant renal prolonged prothrombin time, and evidence of significant renal failurefailure
four of six patients undergoing liver transplantation survived four of six patients undergoing liver transplantation survived for one year, whereas only four of 23 patients with the same for one year, whereas only four of 23 patients with the same clinical indications but who did not receive liver transplantation clinical indications but who did not receive liver transplantation survived for the same period of timesurvived for the same period of time
Dr. Aidah Abu El Soud Alkaissi An-Najah National University
Faculty of Nursing