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Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
Acute intermittent porphyria   case presentation
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Acute intermittent porphyria case presentation

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  • 1. Case presentationA Case of Acute Intermittent Porphyria forElective Caesarean Section By: Dr.Somashekar Reddy.P.V Moderator: Dr.Sushil Bhati, Professor, Dept of Anaesthesia 02/07/13 09:23 Anaesthesia and Porphyria 1
  • 2. History Name: Meenakshi W/o Vikas Plot no 35, Krishna colony, Jaipur Age:25yrs Date of Admission:7th Feb 2012 at Zenana Hospital Reg no.4606,Unit VI Chief complaints: C/o Amenorrhea for 8 months. History of Presenting Illness:I Trimester- No h/o fever, burning micturition, radiation and drug exposure,II Trimester-Tetanus vaccination taken,Foetal movement feltIII Trimester- H/o of increase in BP, on Tab.Labetolol 100mg TDS.No h/o leak pv,bleeding pv,pain abdomen. 02/07/13 09:23 Anaesthesia and Porphyria 2
  • 3. Cont.. Past history: Previous menstrual cycles normal. In 1999, She was admitted in JK Lone hospital with h/o of severe pain abdomen, convulsions(GCTS type,5 episodes, self aborting),Reddish discoloration of urine & Hypertension after intake of a drug for fever and cough. Was admitted in ICU for one week. She was diagnosed with Acute Intermittent Porphyria. Family history- Father and younger sister are also suffering from Porphyria. Three of her siblings passed suddenly away during childhood. 02/07/13 09:23 Anaesthesia and Porphyria 3
  • 4. ExaminationConscious, Oriented, Normal builtNo pallor,icterus,cyanosis,clubbing,edema.PR-80beats per min,BP-136/98mmHg,CVS-S1S2 heard, no murmursRS-B/L air entry equal, no added sounds.P/A- Uniform distention corresponding to34 wks of pregnancyCNS- No focal neurological deficitsSkin- NormalMouth opening was three fingers, no loose teeth, TM joint mobility was normal,MP Grade-INeck movements were normalSpine- Normal. Anaesthesia and Porphyria 02/07/13 09:23 4
  • 5. Investigations Hemoglobin-10.6gm% TLC-7800/mm3 Platelet count-2.6 lac/mm3 RBS-62mg% Blood urea-68mg% S.Creatinine-1.37mg% S.Uric acid-7.63mg% HIV/HbSAg-NegativeDiagnosis Primigravida with 8 months of Pregnancy with Acute Intermittent Porphyria with Pregnancy Induced Hypertension. 02/07/13 09:23 Anaesthesia and Porphyria 5
  • 6. Management Pre anaesthetic evaluation was done one week before the surgery and again on the day of surgery. She was explained about the procedure and the type of anaesthesia in detail. Elective Caesarean Section on 22 feb 2012. Preloaded with 500ml of DNS. Premedication-Inj Ondansetron 4mg. Spinal Anaesthesia was given in L3-L4 space with Hyperbaric Bupivacaine 10mg. Intraoperative vitals maintained within normal limits & patient exhibited no signs of an acute porphyric crisis Inj.Paracetmol was given for Intraoperative & Postoperative analgesia. 02/07/13 09:23 Anaesthesia and Porphyria 6
  • 7. Cont.. The patient was supplied with sufficient amounts of glucose solutions in order to avoid a hypoglycemic state during perioperative and early postoperative period. Postoperative follow up was done for 3 days and patient was discharged home on 28th Feb. 02/07/13 09:23 Anaesthesia and Porphyria 7
  • 8. Discussion The porphyrias are a group of inherited or acquiredenzymatic defects of heme biosynthesis.. Porphyrins are widely distributed throughout the body, they are essential for oxygen transport, electron transport, various oxidation and hydroxylation reactions. Each type of porphyria has a characteristic pattern of overproduction and accumulation of heme precursors based on the location of the dysfunctional enzyme in the heme synthetic pathway . 02/07/13 09:23 Anaesthesia and Porphyria 8
  • 9. Heme Synthesis 02/07/13 09:23 Anaesthesia and Porphyria 9
  • 10.  Heme is a component of microsomal and mitochondrialcytochrome systems and is synthesized and usedin all cells. The two major quantitative sites of hemesynthesis are erythropoeitic and hepatic cells whereheme is incorporated into hemoglobin and hepaticcytochromes. Erythropoeitic porphyrias cause extremeskin sensitivity buy lack neurologic involvementand are not associated with drug-precipitatedcrises. Treatment of known hepatic porphyria consists ofprophylaxis and treatment of the acute attack. 02/07/13 09:23 Anaesthesia and Porphyria 10
  • 11. Classification of Porphyrias1)Hepatic 2)Erythropoietic • Erythropoietic porphyria• Acute intermittent porphyria • Uroporphyria(AIP) • Protoporphyria• Hereditary coproporphyria(HCP)• Variegate porphyria (VP)• ALA dehydratase deficiencyporphyria• Porphyria cutanea tarda Familial Acquired 02/07/13 09:23 Anaesthesia and Porphyria 11
  • 12. Acute Non acuteHepatic acute porphyrias •Erythropoietic Acute intermittent porphyria Erythropoietic porphyria(AIP) Uroporphyria Hereditary coproporphyria Protoporphyria(HCP) •Porphyria cutanea tarda Variegate porphyria (VP) 02/07/13 09:23 Anaesthesia and Porphyria 12
  • 13. Implications for anaesthesia  It might be expected that the cytochrome‐mediated metabolism and high lipid solubility of many anaesthetics would make many of them porphyrinogenic, and anaesthesia has certainly been implicated in the triggering of a number of severe porphyric reactions. Two scenario are possible:1. Case of latent porphyria2. Case of an acute attack 02/07/13 09:23 Anaesthesia and Porphyria 13
  • 14. Acute presentationsCharacterized by severe abdominal pain, autonomic instability, electrolyte disturbance and neuropsychiatric manifestations.Features of the Acute Porphyric Attack1)Nervous system dysfunction Autonomic neuropathy Abdominal pain, Vomiting, Tachycardia, Hypertension, Supine hypotension Peripheral neuropathy Paresis, flaccid quadriplegia, Respiratory Paralysis Bulbar Involment Vagal CN involvment-Dysphagia,Dysphonia, Cerebral Involment Mental status changes,Anxiety,Seizures,Coma2)Lab Changes Dark colour(Reddish) urine,Hyponatremia,Hypokalemia,Hypomagnesemia,Hypochloremia. 02/07/13 09:23 Anaesthesia and Porphyria 14
  • 15. Frequency of symptoms 02/07/13 09:23 Anaesthesia and Porphyria 15
  • 16. Precipitating factors Fasting/dehydration Infection Psychologic stress Physiologic hormone variation Excessive alcohol Smoking Intake, and administration of specific drugs Barbiturates, sulfonamide,anticonvulsants, and oral contraceptives 02/07/13 09:23 Anaesthesia and Porphyria 16
  • 17. Frequency of Precipitating factors 02/07/13 09:23 Anaesthesia and Porphyria 17
  • 18. Pathophysiology of acute attack The manifestions of the disease are thought to be due to increased ALA synthetase activity, increased porphyrin accumulation in the tissues, or decreased heme production . Increased levels of heme precursors(ALA & PBG) proximal to the site of the specific enzyme deficiency. These precursors are highly reactive oxidants and neurotoxic. The accumulation of porphyrins in the epidermal skin layers lead to cutaneous photosensitivity. Acute porphyria often causes severe neuropathy, the basis for multisystem impairment. Changes in autonomic ganglia, anterior horns of the spinal cord,peripheral neves, brainstem nuclei, cerebellar axons,Schwann cells, and myelin sheaths have been demonstrated. Neuronal damage and axonal degeneration may be the primary pathologic lesions, with, later axonal changes leading to secondary demyelination Many hypotheses have been porposed to explain the mechanism of porphyric neuropathy Two of the most plausible attribute the neuronal dysfunction to direct neurotoxicity of ALA , or to diminished intraneuronal heme level or both . 02/07/13 09:23 Anaesthesia and Porphyria 18
  • 19. Diagnostic recommendations Initial diagnosis: The two most important diagnostic recommendations are to1) maintain a high index of suspicion,2) be aware that laboratory testing is available that can readily make a diagnosis of acute porphyria or rule it out Laboratory diagnosis of porphyric crisis can involve fecal analysis& quantification of urinary porphyrin and porphyrinogen precursors Measuring urinary PBG is most important for diagnosis of acute porphyrias 02/07/13 09:23 Anaesthesia and Porphyria 19
  • 20. Treatment: Acute Crisis Reverse factors which increase ALA synthetase activity, Withdrawal of offending drugs, Treatment of symptoms with appropriate medications, Appropriate patient monitoring.Primary Treatment The most effective therapy for the acute attack is hemin or heme arginate .It is specific, because it corrects the deficiency of regulatory heme in the liver and down-regulates ALAS. The standard hemin treatment course is 3-4 mg/kg by vein once daily for 4 days. Intravenous glucose loading (at least 3 L of 10% glucose daily) should be used only for mild attacks or while waiting for Panhematin® to become available 02/07/13 09:23 Anaesthesia and Porphyria 20
  • 21. Cont..1. Hydration,2. Electrolyte imbalance correction,3. Propranolol (which may decrease enzyme activity as well as control hypertension, tachycardia & anxiety)4. Treatment of underlying infection Pain associated with an acute attack is treated by giving opoids. Phenothiazines are used to treat neuro-psychiatric disturbances and vomiting Diazepam, Gabapentin & Vigabatrin has been recommended for acute seizures Magnesium sulfate has been used to control seizures. Mortality in porphyic crises is about 10% with current treatment regimens. 02/07/13 09:23 Anaesthesia and Porphyria 21
  • 22. PregnancyPregnancy may exacerbate or provoke an acute attack.Avoidance of planned pregnancy until I-yr latentperiod has elapsed is recommended. The mortalityrate from acute attack among pregnant patients hasbeen reported to be as high as 42% . 02/07/13 09:23 Anaesthesia and Porphyria 22
  • 23. Recommendations applied to drugsCategory DescriptionUse Drug is safe & can be used freelyUse with caution (UWC) Safety is not established beyond doubt ,the evidence suggests that drug is unlike to prove unsafe.it may be used if safe alternative is not availableUse with Extreme Caution Only Evidence suggest that drug may(UWECO) prove unsafe or little evidence is available to prove it safe.should only be used if benefits overweigh risks and adverse outcome must be anticipated.Avoid There is evidence that such drugs have precipitated acute attackNo Data/ Avoid There is too little evidence to draw a conclusion 02/07/13 09:23 Anaesthesia and Porphyria 23
  • 24. Premedication Prolonged fasting in the pre-operative period should be avoided where possible. Glucose-saline should be administered by infusion; 5% dextrose is hypotonic and is best avoided, since hyponatraemia is associated with acute attacks and a risk of further electrolyte imbalance. Inj Midazolam used for premedication are considered safe. Phenothiazines may have particular advantage. When antacid administration is considered appropriate, Sodium Citrate may be given & Inj.Ranitidine can be given. Metoclopromide should be avoided. 02/07/13 09:23 Anaesthesia and Porphyria 24
  • 25. Regional anaesthesia Acute porphyria is not an absolute contraindication to regional anesthesia but in the setting of peripheral neuropathy, detailed preoperative exmination and documentation is essential. Mental status should be normal. Regional anesthesia should probably be avoided in the setting of acute porphyric crisis. Hypovolemia and a labile autonomic response, characteristic of acute porphyric crisis, increase therisk of hemodynamic instability in the setting of a sympathectomy. 02/07/13 09:23 Anaesthesia and Porphyria 25
  • 26. •Regional Anaesthesia Cont.. Bupivacaine is considered safe for regional anesthesia. Although some evidence suggests that lidocaine may increase ALA synthetase activity in animal tissue culture cells, no clincial exacerbations have been reported. Ropivacaine should be avoided. Prilocaine, Tetracaine & Procaine are safe 02/07/13 09:23 Anaesthesia and Porphyria 26
  • 27. General anaesthesiaIntraveous Induction Agents The barbiturates are the inducers of ALA synthetase, and all barbiturates, including thiopental, must be considered unsafe. Etomidate is potentially porphyrinogenic in animal models,so it should be avoided. Ketamine is probably safe; However, an increase in ALA, PBG and other porphyrins after ketamine has been reported in a patient in the latent phase of AIP, and it would seem wise to reserve ketamine for use where hemodynamic or other considerations make it the drug of choice Protocol can safely be used for induction of anaesthesia. 02/07/13 09:23 Anaesthesia and Porphyria 27
  • 28. Inhalational agentsNitrous oxide UseCyclopropane UseHalothane UseIsoflurane UWCEnflurane UWCSevoflurane UWCDesflurane UWC Halothane would appear to be the current agent of choice, and isoflurane may be a satisfactory alternative 02/07/13 09:23 Anaesthesia and Porphyria 28
  • 29. Neuromuscular Blockers Succinylcholine Use d- Tubocurarine Use Pancuronium Use Atracurium UWC Rocuronium UWC Mivacurium UWC Vecuronium UWC 02/07/13 09:23 Anaesthesia and Porphyria 29
  • 30. Analgesic agents Acetaminophen Use Alfenanil Use Aspirin Use Indomethcin Use Buprenorphine Use Codiene Use Fentanyl Use Pethidine Use Morphine Use Naloxone Use Sufentanil Use Pentazocine Avoid Brufen UWC Diclofenac UWECO Ketorolac UWECO Phenacetin UWECO 02/07/13 09:23 Anaesthesia and Porphyria 30
  • 31. Cardiovascular Drugs Epinephrine,Magnesium,Phentolamine,Procainamide,alpha agonists, beta blockers & agonists are safe. Diltizem,Disopyramide,Sodium Nitroprusside & Verapamil should be used with caution. Nifidepine, alpha methyl dopa & Hydralazine should be avoided.NM Block Reversal agents Atropine,Glycopyrolate & Neostigmine can be used safely. 02/07/13 09:23 Anaesthesia and Porphyria 31
  • 32. Inadvertent use of porphyrinogenic drugs It is recommended that oral carbohydrate supplements should be given with a target of 200 kcal 24 h–1. If oral feeding is impossible, a 10% dextrose–saline infusion should be given. The patient should be monitored carefully with urine sampling for porphyrins for at least 5 days and supportive therapy given if necessary. 02/07/13 09:23 Anaesthesia and Porphyria 32
  • 33. Postoperative Management Monitoring for the potential onset of porphyric crisis should be continued for up to 5 days, since onset may be delayed. 02/07/13 09:23 Anaesthesia and Porphyria 33
  • 34. Conclusion The acute porphyrias are rare but they are important in anaesthesia because of the wide range of agents that can trigger an acute crisis. If an acute attack is suspected,immediate empherical therapy should be started The simplest course for the practising anaesthetist to adopt is not to attempt to remember a large range of drugs that are potentially hazardous, but rather to develop a simple, safe technique based on agents that have minimal risk of triggering a porphyric crisis The choice of agent may be based more on the patient’s anaesthetic and surgical requirements, rather than governed by the specific requirements imposed by porphyria. Any suspicion must lead to diagnosis assessment and possibly to research into the family history. 02/07/13 09:23 Anaesthesia and Porphyria 34
  • 35. Thankyou 02/07/13 09:23 Anaesthesia and Porphyria 35

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