1. Case presentation
A Case of Acute Intermittent Porphyria for
Elective Caesarean Section
By: Dr.Somashekar Reddy.P.V
Moderator: Dr.Sushil Bhati,
Professor, Dept of Anaesthesia
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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 felt
III Trimester- H/o of increase in BP, on Tab.Labetolol 100mg TDS.
No h/o leak pv,bleeding pv,pain abdomen.
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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.
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4. Examination
Conscious, Oriented, Normal built
No pallor,icterus,cyanosis,clubbing,edema.
PR-80beats per min,
BP-136/98mmHg,
CVS-S1S2 heard, no murmurs
RS-B/L air entry equal, no added sounds.
P/A- Uniform distention corresponding to34 wks of pregnancy
CNS- No focal neurological deficits
Skin- Normal
Mouth opening was three fingers, no loose teeth, TM joint mobility was
normal,MP Grade-I
Neck movements were normal
Spine- Normal.
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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-Negative
Diagnosis
Primigravida with 8 months of Pregnancy with Acute
Intermittent Porphyria with Pregnancy Induced
Hypertension.
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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.
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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.
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8. Discussion
 The porphyrias are a group of inherited or acquired
enzymatic 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 .
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9. Heme Synthesis
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10.  Heme is a component of microsomal and mitochondrial
cytochrome systems and is synthesized and used
in all cells.
 The two major quantitative sites of heme
synthesis are erythropoeitic and hepatic cells where
heme is incorporated into hemoglobin and hepatic
cytochromes.
 Erythropoeitic porphyrias cause extreme
skin sensitivity buy lack neurologic involvement
and are not associated with drug-precipitated
crises.
 Treatment of known hepatic porphyria consists of
prophylaxis and treatment of the acute attack.
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11. Classification of Porphyrias
1)Hepatic 2)Erythropoietic
• Erythropoietic porphyria
• Acute intermittent porphyria • Uroporphyria
(AIP) • Protoporphyria
• Hereditary coproporphyria
(HCP)
• Variegate porphyria (VP)
• ALA dehydratase deficiency
porphyria
• Porphyria cutanea tarda
Familial
Acquired
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12. Acute Non acute
Hepatic acute porphyrias •Erythropoietic
Acute intermittent porphyria Erythropoietic porphyria
(AIP) Uroporphyria
Hereditary coproporphyria Protoporphyria
(HCP) •Porphyria cutanea tarda
Variegate porphyria (VP)
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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 porphyria
2. Case of an acute attack
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14. Acute presentations
Characterized by severe abdominal pain, autonomic instability, electrolyte
disturbance and neuropsychiatric manifestations.
Features of the Acute Porphyric Attack
1)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,Coma
2)Lab Changes
Dark colour(Reddish) urine,Hyponatremia,Hypokalemia,Hypomagnesemia,
Hypochloremia.
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15. Frequency of symptoms
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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
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17. Frequency of Precipitating factors
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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 .
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19. Diagnostic recommendations
 Initial diagnosis:
 The two most important diagnostic recommendations are to
1) 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
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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
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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.
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22. Pregnancy
Pregnancy may exacerbate or provoke an acute attack.
Avoidance of planned pregnancy until I-yr latent
period has elapsed is recommended. The mortality
rate from acute attack among pregnant patients has
been reported to be as high as 42% .
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23. Recommendations applied to drugs
Category Description
Use Drug is safe & can be used freely
Use 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 available
Use 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 attack
No Data/ Avoid There is too little evidence to draw a
conclusion
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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.
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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 the
risk of hemodynamic instability in the setting of a sympathectomy.
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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
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27. General anaesthesia
Intraveous 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.
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28. Inhalational agents
Nitrous oxide Use
Cyclopropane Use
Halothane Use
Isoflurane UWC
Enflurane UWC
Sevoflurane UWC
Desflurane UWC
 Halothane would appear to be the current agent of choice, and
isoflurane may be a satisfactory alternative
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29. Neuromuscular Blockers
 Succinylcholine Use
 d- Tubocurarine Use
 Pancuronium Use
 Atracurium UWC
 Rocuronium UWC
 Mivacurium UWC
 Vecuronium UWC
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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
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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.
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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.
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33. Postoperative Management
 Monitoring for the potential onset of porphyric crisis
should be continued for up to 5 days, since onset may
be delayed.
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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.
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35. Thankyou
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